bluuebunny/crossref_metadata_2025 huggingface dataset:
Increasing rational use of cholinesterase inhibitors for Alzheimer's disease in Brazil: Public health strategy combining guideline with peer-review of prescriptions
Authors: Picon Paulo Dornelles , Camozzato Ana Luiza , Lapporte Elaine A. , Picon Rafael V. , Filho Humberto Moser , Cerveira Maria Otília , Chaves Márcia L. F.
Published: April 2010

Objectives:Since 2002, the treatment with cholinesterase inhibitors (CHEIs) for Alzheimer's disease (AD) has been paid for by the public health system of the Brazilian Ministry of Health for any patient that fulfills clinical criteria established by an evidence-based guideline developed and published by the Ministry. The aim of this study was to evaluate compliance of prescription patterns to the national guideline for use of CHEIs’ in the southern Brazilian state of Rio Grande do Sul.

Methods:We created a regional expert-committee reference center to review all prescriptions of CHEIs and to send feedback to physicians whenever prescriptions without compliance to the guideline were noted. One thousand three hundred ninety-nine (1,399) CHEI prescriptions presented to the public health system from 2005 to 2007 were evaluated by an expert team of neurologists and psychiatrists. Clinical history, performance on mental status screening by Mini Mental State Examination (MMSE), Clinical Dementia Rating scale (CDR), laboratory results, and neuroimaging findings were evaluated in relation to the adherence to the national guideline's recommendations. If the prescription was rejected because of lack of adherence to the criteria of the guideline, a written response was sent by the expert committee to physicians concerning the request.

Results:The majority of the requests (n= 1,044; 75 percent) did not meet the AD guideline's criteria, either for diagnosis or for treatment, and were not granted. A diagnostic mistake was evident in 64.3 percent of cases. Findings of vascular or Parkinson's dementia or severe AD were the main reasons for rejection. Rivastigmine was the most prescribed cholinesterase inhibitor, used in 86 percent of cases. Of note was the reduction in the number of CHEIs prescriptions in the years following this intervention.

Conclusions:The public health strategy of using expert-review of prescriptions and their compliance to national guideline revealed a low rate of rational use of CHEIs for dementia. Such a strategy is relevant for protecting patients from unproven medical interventions and for reducing waste of resources.
HTA in the United Kingdom
Authors: Gabbay John
Published: April 2010

I was dismayed to find that the article on HTA in the United Kingdom in the recent Special Issus of IJTAHC on the History of HTA (1) makes so little mention of the main component of HTA in England and Wales, namely the NHS HTA Programme. That seems a puzzling oversight for a program that, since its inception in 1993, has spent 138 million GBP on commissioning nearly 850 in-depth HTA studies, sifted and prioritized from some 15,000 suggestions drawn from all quarters of UK health service, policy, and research worlds. From these, it has published nearly 500 full-length HTA monographs (with over 125 more currently in editorial review) in the series Health Technology Assessment, which has attracted over 15 million downloads as well as being distributed in hard copy to just over 128,000 recipients. Around 120 of these monographs resulted from research commissioned explicitly to advance the methodology of HTA—a contribution that is unique among the world's HTA agencies. This stream of HTA publications, which has also spawned countless summaries, local adaptations, translations, academic papers, and other spinoffs, has had an acknowledged impact throughout the world of HTA.
Harmonizing HTA
Authors: Pasternack Iris , Lampe Kristian , de Laet Chris , Cleemput Irina , Neyt Mattias , Wild Claudia , Kristensen Finn Børlum
Published: April 2010

Paul Trueman and colleagues (3) have reported on an important issue. Several HTAs on the same topic have been published recently. They have examined four recent HTA reports on drug-eluting stents (DES), demonstrating varying methods and conclusions. All four HTAs included local registry data and economic evaluations in addition to analyses of published research. The authors concluded that the published evidence considered by most of the agencies had “only limited influence on the resulting recommendations.”
Options for improving malaria treatment: Introduction
Authors: Oxman Andrew D. , Yohannes Ambachew M. , Røttingen John-Arne
Published: April 2010

This Theme Section of IJTAHC presents summaries of six policy briefs that address scaling up of artemisinin-based combination therapies (ACTs) in the treatment of uncomplicated falciparum malaria in Africa. The methods used to develop the policy briefs are described in the Section Editorial. Each summary assesses the problem, potential policy options to address the problem, and strategies for implementing those options.
Policy brief on improving access to artemisinin-based combination therapies for malaria control in Ethiopia
Authors: Kebede Amha , Woyessa Adugna , Urga Kelbessa , Messelle Tsehaynesh , Jima Daddi
Published: April 2010

Malaria in Ethiopia is one of the leading causes of death (21.8 percent), consultation in outpatient departments (17.8 percent) and hospital admissions (14.1 percent) (2;14). To overcome this problem, the Malaria Control Program (Federal Ministry of Health) has designed a community-based malaria treatment approach that played key roles in malaria epidemic control and community mobilization as well as vector control operations. In this approach, Community Health Workers (CHWs) and Village Malaria Workers, volunteers selected by community and trained on malaria diagnosis and treatment as well as indoor residual spray for few days (16). However, sustainability of this approach has been a challenge to the malaria control program. Thus, institutional arrangements in which every Kebele (the smallest administrative unit of 5,000 people) has a health post staffed by two Health Extension Workers (HEW) as part of the country's health system is a breakthrough to strengthen malaria control. A study has shown that more than half of the patients with fever visit CHWs and private health facility services (4).
Policy brief on improving access to artemisinin-based combination therapies for malaria in Central African Republic
Authors: Gresenguet Gérard , Moyen Méthode , Koffi Boniface , Bangamingo Jean Pierre
Published: April 2010

In the Central African Republic (CAR) malaria is a major public health problem and hampers socioeconomic development. It accounts for 40 percent of complaints and 10 percent of deaths in health facilities (15;17). Pregnant women, who make up 4 percent of the population, and children under 5 years of age, who represent 17.3 percent, are the groups most vulnerable to malaria owing to their low levels of immunity.
Spatial analysis of notified dengue fever infections
Authors: HU W. , CLEMENTS A. , WILLIAMS G. , TONG S.
Published: April 2010

This study aimed to investigate the spatial clustering and dynamic dispersion of dengue incidence in Queensland, Australia. We used Moran'sIstatistic to assess the spatial autocorrelation of reported dengue cases. Spatial empirical Bayes smoothing estimates were used to display the spatial distribution of dengue in postal areas throughout Queensland. Local indicators of spatial association (LISA) maps and logistic regression models were used to identify spatial clusters and examine the spatio-temporal patterns of the spread of dengue. The results indicate that the spatial distribution of dengue was clustered during each of the three periods of 1993–1996, 1997–2000 and 2001–2004. The high-incidence clusters of dengue were primarily concentrated in the north of Queensland and low-incidence clusters occurred in the south-east of Queensland. The study concludes that the geographical range of notified dengue cases has significantly expanded in Queensland over recent years.
New rabies virus variant found during an epizootic in white-nosed coatis from the Yucatan Peninsula
Authors: ARÉCHIGA-CEBALLOS N. , VELASCO-VILLA A. , SHI M. , FLORES-CHÁVEZ S. , BARRÓN B. , CUEVAS-DOMÍNGUEZ E. , GONZÁLEZ-ORIGEL A. , AGUILAR-SETIÉN A.
Published: April 2010

In February 2008, three white-nosed coatis (Nasua narica) were found dead in a recreational park in Cancun, Mexico. The diagnosis of rabies virus (RABV) infection was confirmed by direct immunofluorescence test. The phylogenetic analysis performed with the complete RABV nucleoprotein gene positioned this isolate close to a sequence of a human rabies case reported during 2008 from Oaxaca, Mexico, sharing 93% similarity. In turn, these two variants are related to another variant found in rabidTadarida brasiliensis mexicanabats across North America. Anti-RABV neutralizing activity (1·3 IU/ml) was found in the serum of one white-nosed coati captured with another five that cohabited with the dead animals. Enhanced rabies surveillance and pathogenesis studies should be conducted in coatis and insectivorous bats of the region to clarify the role of these species as potential emergent or long-term unidentified RABV reservoirs.
Bovine tuberculosis: making a case for effective surveillance
Authors: PROBST C. , FREULING C. , MOSER I. , GEUE L. , KÖHLER H. , CONRATHS F. J. , HOTZEL H. , LIEBLER-TENORIO E. M. , KRAMER M.
Published: April 2010

In 2008, a cow with marked gross lesions suspicious for bovine tuberculosis (bTB) was identified by meat inspection at home slaughtering in north-western Germany. Epidemiological investigations led to the identification of another 11 affected farms with a total of 135 animals which reacted positive to the skin test. Eight affected farms had been in trade contact with the putative index farm. While the source for the initial introduction remained unknown, it was shown that all isolates tested shared the same molecular characteristics suggesting a common source of infection. The findings demonstrate that bTB can easily be transmitted via animal trade and may remain undetected for years in herds in the absence of tuberculin testing. Hence, we believe that bTB surveillance should not rely only on meat inspection, but on a combination of both meat inspection and intradermal tuberculin testing.
Diversity of State-Religion Relations and European Union Unity
Authors: Robbers Gerhard
Published: April 2010

There is no single system of state-religion relations within Europe which is equal to another. Each one is distinct. Many countries know a number of different systems within themselves, as does the United Kingdom, Germany or France. The presence of history is strongest perhaps in this field of life. Tradition and truth, emotion and identity flourish in this field. Future law on religion in Europe is best built on strong regional structures. This paper reports on three aspects of state-religion relations in Europe: What is the situation in Germany? What does the United Kingdom look like from the continent? And what about Europe?
A random walk in the literature on criminality: A partial and critical view on some statistical analyses and modelling approaches
Authors: GORDON M. B.
Published: April 2010

We are interested in the possible contributions of mathematical modelling of crime. We refer to numerous and quite recent papers that analyse and discuss empirical data in an attempt to discover stylised trends worthy of being understood through simple models. We summarise part of this literature and try to understand the reasons of important discrepancies in their conclusions. Then we present some recent modelling attempts that may help to understand the large variance in the statistical-based conclusions.
A brief history of the analysis of crime concentration
Authors: JOHNSON SHANE D.
Published: April 2010

Decades of research demonstrate that crime is concentrated at a range of spatial scales. Such findings have clear implications for crime forecasting and police resource allocation models. More recent work has also shown that crime clusters in spaceandtime with a regularity that might improve methods of crime prediction. In this paper I review some of the available evidence and provide illustrations of the types of analysis – spatial and spatio-temporal – conducted hitherto. With a few exceptions, the application of formal Mathematics in the study of space–time patterns of crime has been rather limited, and so a central aim of the paper is to stimulate interest in this area of research.
Parametricity, type equality, and higher-order polymorphism
Authors: VYTINIOTIS DIMITRIOS , WEIRICH STEPHANIE
Published: April 2010

Propositions that express type equality are a frequent ingredient of modern functional programming – they can encode generic functions, dynamic types, and GADTs. Via the Curry–Howard correspondence, these propositions are ordinarytypesinhabited by proofterms, computed using runtime type representations. In this paper we show that two examples of type equality propositions actually do reflect type equality; they are only inhabited when their arguments are equal and their proofs are unique (up to equivalence.) We show this result in the context of a strongly normalizing language with higher-order polymorphism and primitive recursion over runtime-type representations by proving Reynolds's abstraction theorem. We then use this theorem to derive “free” theorems about equality types.
“DixieCarmen”: War, Race, and Identity in Oscar Hammerstein'sCarmen Jones(1943)
Authors: FAUSER ANNEGRET
Published: April 2010

In December 1943, an all–African American cast starred in the Broadway premiere ofCarmen Jones, Oscar Hammerstein II's adaptation of Georges Bizet'sCarmen. When Hammerstein began work onCarmen Jonesa month after Pearl Harbor, in January 1942,Porgy and Besswas just being revived. Hammerstein's 1942 version ofCarmen, set in a Southern town and among African Americans, shows the influence of the revised version ofPorgy and Bess, with Catfish Row echoed in a cigarette factory in South Carolina and the Hoity Toity night club. It took Hammerstein more than eighteen months to find a producer, and when the show opened by the end of 1943, the setting in a parachute factory and urban Chicago reflected new priorities brought on by wartime changes. Commercially one of the most successful musical plays on Broadway during its run of 503 performances,Carmen Jonesoffers a window on the changing issues of culture, class, and race in the United States during World War II. New archival evidence reveals that these topics were part of the work's genesis and production as much as of its reception. This article contextualizesCarmen Jonesby focusing on the complex issues of war, race, and identity in the United States in 1942 and 1943.
“Some of These Days” and the Study of the Great American Songbook
Authors: GARBER MICHAEL
Published: April 2010

Supporting a new methodology for the study of classic American popular songs, this article offers a history of both the print editions and recorded versions of “Some of These Days” (1910) by Shelton Brooks. This saga commences with a hitherto unanalyzed precursor to Brooks's famous song that shares nearly the same opening words and melody, the 1905 “Some o' Dese Days” by Frank Williams. It continues through nine major print editions and numerous recorded performances, of which this study examines forty-six, including ten as the theme song for Sophie Tucker. Performers are clearly influenced by both performed and printed variations; more surprisingly, print editions are also influenced by performers. Thus, Tin Pan Alley songs are best viewed as products of collaboration within a community of songwriters, publishers, and performers. Brooks fills “Some of These Days” with compositional details that are conducive to effective performance variations. This elusive intrinsic adaptability represents, for 1910, a modern, innovative quality and is central to any understanding of this song genre. Oft-neglected, such early popular standards—poised at the juncture of musical cultures, oral and print, amateur and professional, live and mediatized—help the critical historian pinpoint aspects that make this repertoire valuable.
An Interrogation of Language: “Radical Jewish Culture” on New York City's Downtown Music Scene
Authors: BARZEL TAMAR
Published: April 2010

In April 1993 the Knitting Factory, a small nightclub in Lower Manhattan, hosted a five-day music festival titled “Radical New Jewish Culture.” This event was part of a multifaceted creative endeavor undertaken during the 1990s by composer/improvisers on New York City's downtown music scene and dubbed “Radical Jewish Culture” by its main protagonist, saxophonist John Zorn. RJC brought Jewish music and heritage into the purview of a polycultural experimentalist scene shaped by jazz, rock, free improvisation, and avant-garde concert music. Artists downtown also engaged in an animated “conversational community” that spilled over into interviews, program notes, liner notes, and essays. RJC was especially productive as a conceptual framework from which to interrogate the relationship between musical language and the semiotics of sound. Two pieces serve here as case studies: “¡Bnai!” an Israeli “pioneer song” as interpreted by the No Wave band G-d Is My Co-Pilot, and “The Mooche,” a Duke Ellington/Bubber Miley composition as interpreted by pianist Anthony Coleman's Selfhaters Orchestra.
Women fighters and the ‘beautiful soul’ narrative
Authors: Sjoberg Laura
Published: April 2010

This article explores women's presence in military forces around the world, looking both at women's service as soldiers and at the gendered dimensions of their soldiering particularly, and soldiering generally. It uses the ‘beautiful soul’ narrative to describe women's relationship with war throughout its history, and explores how this image of women's innocence of and abstention from war has often contrasted with women's actual experiences as soldiers and fighters.
Einfluss der Aufgabenpriorisierung auf die Haltungskontrolle unter Doppeltätigkeitsbedingung
Authors: Wehrle Anja , Granacher Urs , Mühlbauer Thomas
Published: April 2010

Zusammenfassung. Gegenstand der Studie war die Überprüfung des Einflusses der Aufgabenpriorisierung auf die Haltungskontrolle unter Doppeltätigkeitsbedingung. Hierzu wurden bei jungen und gesunden Erwachsenen (N = 60) das Gleichgewicht und die Leistung beim Rückwärtsrechnen einzeln (Einfachtätigkeit) sowie simultan (Doppeltätigkeit) unter drei verschiedenen Priorisierungsbedingungen getestet. In der ersten Bedingung sollte die Aufmerksamkeit auf die Gleichgewichtsaufgabe (Gruppe: „Stehen”) und in der zweiten Bedingung auf die kognitive Aufgabe (Gruppe: „Rechnen”) gerichtet werden. In der dritten Bedingung sollte eine Aufmerksamkeitslenkung auf beide Aufgaben erfolgen (Gruppe: „Stehen+Rechnen”). Im Ergebnis zeigten sich weder im Schwankungsverhalten noch in der Rechenleistung statistisch signifikante Gruppenunterschiede. Diese Befunde sind konsistent mit Studien, in denen gleiche motorische, aber andere kognitive Aufgaben verwendet wurden, was auf das Vorliegen eines relativ robusten Phänomens hindeutet. Da Personen in alltäglichen Doppeltätigkeitssituationen bestrebt sind, beide Aufgaben bestmöglich auszuführen, sollte insbesondere in Testsituationen mit funktioneller Relevanz der Priorisierung beider Aufgaben Vorzug gegenüber einer anderen Aufmerksamkeitslenkung gegeben werden.
Entwicklungsbedingte Koordinationsstörungen
Authors: Kastner Julia , Petermann Franz
Published: April 2010

Zusammenfassung. Der aktuelle Forschungsstand deutet darauf hin, dass entwicklungsbedingte Koordinationsstörungen häufig mit psychischen und sozialen Verhaltensauffälligkeiten sowie kognitiven Defiziten verknüpft sind; insbesondere der Kontakt zur Gleichaltrigengruppe scheint problematisch. Die vorliegende Studie überprüft, ob betroffene Kinder spezifische kognitive Defizite sowie verschiedene Verhaltensprobleme aufweisen. Es besteht die Hypothese, dass psychische Auffälligkeiten sowie Probleme im sozialen Bereich nicht nur unmittelbare Folgen der motorischen Ungeschicklichkeit darstellen, sondern dass bestimmte kognitive Defizite an der Entstehung dieser negativen Begleiterscheinungen beteiligt sind. In der Studie wurden 35 koordinationsgestörte Kinder im Alter von sechs bis elf Jahren mit einer alters- und geschlechtsgematchten Kontrollgruppe (n = 35) anhand ihrer kognitiven Leistungen, ihres Sozialverhaltens sowie bestimmter psychischer Verhaltensauffälligkeiten mittels t-Tests verglichen. Zur Absicherung der Diagnose einer entwicklungsbedingten Koordinationsstörung wurde der Motoriktest Movement Assessment Battery for Children (M-ABC-2) eingesetzt. Die Überprüfung der kognitiven Leistungen erfolgte mittels des Hamburg-Wechsler-Intelligenztest für Kinder – IV (HAWIK-IV). Psychische und soziale Verhaltensabweichungen wurden mithilfe des Elternfragebogens der Intelligence and Developmental Scales (IDS) und der Lehrereinschätzliste (LSL) erfasst. Anhand von Mediatoranalysen wird überprüft, ob ein indirekter Zusammenhang zwischen motorischer Leistung und verschiedenen Verhaltensauffälligkeiten besteht, der durch bestimmte kognitive Defizite vermittelt wird. Die Kinder weisen im Vergleich zur Kontrollgruppe ein erhöhtes Maß an psychischen Auffälligkeiten, Einschränkungen im Sozialverhalten sowie signifikante Intelligenzunterschiede auf. Das Wahrnehmungsgebundene Logische Denken (HAWIK-IV) vermittelt den Zusammenhang zwischen der motorischen Gesamtleistung sowie den LSL-Skalen Einfühlungsvermögen und Kooperation. Die Ergebnisse weisen darauf hin, dass verschiedene Wahrnehmungsdefizite den Umgang mit der Gleichaltrigengruppe erschweren.
On the quantitative analysis and evaluation of magnetic hysteresis data
Authors: Jackson Mike , Solheid Peter
Published: April 2010

Magnetic hysteresis data are centrally important in pure and applied rock magnetism, but to date, no objective quantitative methods have been developed for assessment of data quality and of the uncertainty in parameters calculated from imperfect data. We propose several initial steps toward such assessment, using loop symmetry as an important key. With a few notable exceptions (e.g., related to field cooling and exchange bias), magnetic hysteresis loops possess a high degree of inversion symmetry (M(H) = −M(−H)). This property enables us to treat the upper and lower half‐loops as replicate measurements for quantification of random noise, drift, and offsets. This, in turn, makes it possible to evaluate the statistical significance of nonlinearity, either in the high‐field region (due to nonsaturation of the ferromagnetic moment) or over the complete range of applied fields (due to nonnegligible contribution of ferromagnetic phases to the total magnetic signal). It also allows us to quantify the significance of fitting errors for model loops constructed from analytical basis functions. When a statistically significant high‐field nonlinearity is found, magnetic parameters must be calculated by approach‐to‐saturation fitting, e.g., by a model of the form M(H) = Ms + χHFH + αHβ. This nonlinear high‐field inverse modeling problem is strongly ill conditioned, resulting in large and strongly covariant uncertainties in the fitted parameters, which we characterize through bootstrap analyses. For a variety of materials, including ferrihydrite and mid‐ocean ridge basalts, measured in applied fields up to about 1.5 T, we find that the calculated value of the exponent β is extremely sensitive to small differences in the data or in the method of processing and that the overall uncertainty exceeds the range of physically reasonable values. The “unknowability” of β is accompanied by relatively large uncertainties in the other parameters, which can be characterized, if not rigorously quantified, through the bootstrapped distribution of best fit models. Nevertheless, approach‐to‐saturation fitting yields much more accurate estimates of important parameters like Ms than those obtained by linear M(H) fitting and should be used when maximum available fields are insufficient to reach saturation.
A further study of the tropical Indian Ocean asymmetric mode in boreal spring
Authors: Wu Renguang , Yeh Sang‐Wook
Published: April 2010

The present study performs a mixed‐layer heat budget analysis and a hybrid coupled model experiment to understand the roles of surface heat fluxes and oceanic processes in the tropical Indian Ocean asymmetric mode in boreal spring. The heat budget analysis shows that the surface heat fluxes play a dominant role in sea surface temperature (SST) changes in most of the tropical Indian Ocean. In the southwest tropical Indian Ocean, the SST warming during October–November that initiates the cross‐equatorial SST gradient for the development of the asymmetric mode is primarily due to surface latent heat flux, with secondary contribution from meridional and vertical advection. The SST warming around April that sustain the cross‐equatorial SST gradient is also mainly due to latent heat flux. The ocean downwelling is large during late winter and boreal spring, which prevents the weakening of the SST anomalies. The results of a numerical experiment with a hybrid coupled model in which an atmospheric general circulation model is coupled to a slab ocean model in the tropical Indian Ocean demonstrates that the asymmetric mode can develop without ocean dynamics. Thus, the thermodynamic air‐sea interactions play an essential role for the development of the tropical Indian Ocean asymmetric mode.
Detecting thin cirrus in Multiangle Imaging Spectroradiometer aerosol retrievals
Authors: Pierce Jeffrey R. , Kahn Ralph A. , Davis Matt R. , Comstock Jennifer M.
Published: April 2010

Thin cirrus clouds (optical depth (OD) < 0.3) are often undetected by standard cloud masking in satellite aerosol retrieval algorithms. However, the Multiangle Imaging Spectroradiometer (MISR) aerosol retrieval has the potential to discriminate between the scattering phase functions of cirrus and aerosols, thus separating these components. Theoretical tests show that MISR is sensitive to cirrus OD within Max{0.05, 20%}, similar to MISR's sensitivity to aerosol OD, and MISR can distinguish between small and large crystals, even at low latitudes, where the range of scattering angles observed by MISR is smallest. Including just two cirrus components in the aerosol retrieval algorithm would capture typical MISR sensitivity to the natural range of cirrus properties; in situations where cirrus is present but the retrieval comparison space lacks these components, the retrieval tends to underestimate OD. Generally, MISR can also distinguish between cirrus and common aerosol types when the proper cirrus and aerosol optical models are included in the retrieval comparison space and total column OD is >∼0.2. However, in some cases, especially at low latitudes, cirrus can be mistaken for some combinations of dust and large nonabsorbing spherical aerosols, raising a caution about retrievals in dusty marine regions when cirrus is present. Comparisons of MISR with lidar and Aerosol Robotic Network show good agreement in a majority of the cases, but situations where cirrus clouds have optical depths >0.15 and are horizontally inhomogeneous on spatial scales shorter than ∼50 km pose difficulties for cirrus retrieval using the MISR standard aerosol algorithm.
Reexamining the relationship between Apollinaris Patera and the basalts of the Gusev crater plains, Mars
Authors: Lang Nicholas P. , McSween Harry Y. , Tornabene Livio L. , Hardgrove Craig J. , Christensen Philip R.
Published: April 2010

A possible source of the Gusev crater basalts analyzed by the Spirit rover is Apollinaris Patera. We test this hypothesis by identifying and analyzing potential lava flow paths using Thermal Emission Imaging System, Mars Orbiter Camera, High Resolution Imaging Science Experiment, and Mars Orbiter Laser Altimeter data sets together with published geologic mapping. Image interpretation reveals three possible flow paths from Apollinaris onto Gusev crater floor via a breach in Gusev's northwest rim; an unnamed crater that must have postdated any potential flow along the paths currently blocks the breach. After correcting for the unnamed crater, topographic profiles constructed along possible flow paths demonstrate that elevation along each path increases from ∼80 to 430 m. For two of the pathways, this elevation change indicates that lavas could not have traversed through them. The third profile, though, is less conclusive as the topography may reflect a broad flexural arch. However, on the basis of two of the topographic profiles together with the lack of obvious lava flow structures that indicate flow south through the breach, we propose that Apollinaris was not the direct source of the Gusev basalts. Instead, we argue that it seems more likely that the Gusev basalts were sourced from below the crater itself. The similar ages (as derived from crater counts) of Apollinaris's south flank and the Gusev plains lavas, however, suggest that the two volcanic regions may be part of a common magmatic feature.
Can molecular diffusion explain Space Shuttle plume spreading?
Authors: Meier R. R. , Plane John M. C. , Stevens Michael H. , Paxton L. J. , Christensen A. B. , Crowley G.
Published: April 2010

The satellite‐borne Global Ultraviolet Imager (GUVI) has produced more than 20 images of NASA Space Shuttle main engine plumes in the lower thermosphere. These reveal atomic hydrogen and, by inference, water vapor transport over hemispherical‐scale distances with speeds much faster than expected from models of thermospheric wind motions. Furthermore, the hydrogen plumes expand rapidly. We find rates that exceed the horizontal diffusion speed at nominal plume altitudes of 104‐112 km. Kelley et al. (2009) have proposed a 2‐D turbulence mechanism to explain the observed spreading rates (and rapid advection) of the plumes. But upon further investigation, we conclude that H atom diffusion can indeed account for the observed expansion rates by recognizing that vertical diffusion quickly conveys atoms to higher altitudes where horizontal diffusion is much more rapid. We also find evidence for H atom production directly during the Shuttle's main engine burn.
Significant CO2 fixation by small prymnesiophytes in the subtropical and tropical northeast Atlantic Ocean
Authors: Jardillier Ludwig , Zubkov Mikhail V , Pearman John , Scanlan David J
Published: April 2010

Global estimates indicate the oceans are responsible for approximately half of the carbon dioxide fixed on Earth. Organisms ⩽5 μm in size dominate open ocean phytoplankton communities in terms of abundance and CO2 fixation, with the cyanobacterial genera Prochlorococcus and Synechococcus numerically the most abundant and more extensively studied compared with small eukaryotes. However, the contribution of specific taxonomic groups to marine CO2 fixation is still poorly known. In this study, we show that among the phytoplankton, small eukaryotes contribute significantly to CO2 fixation (44%) because of their larger cell volume and thereby higher cell-specific CO2 fixation rates. Within the eukaryotes, two groups, herein called Euk-A and Euk-B, were distinguished based on their flow cytometric signature. Euk-A, the most abundant group, contained cells 1.8±0.1 μm in size while Euk-B was the least abundant but cells were larger (2.8±0.2 μm). The Euk-B group comprising prymnesiophytes (73±13%) belonging largely to lineages with no close cultured counterparts accounted for up to 38% of the total primary production in the subtropical and tropical northeast Atlantic Ocean, suggesting a key role of this group in oceanic CO2 fixation.
Freshwater Perkinsea and marine-freshwater colonizations revealed by pyrosequencing and phylogeny of environmental rDNA
Authors: Bråte Jon , Logares Ramiro , Berney Cédric , Ree Dan Kristofer , Klaveness Dag , Jakobsen Kjetill S , Shalchian-Tabrizi Kamran
Published: April 2010

Protist parasites are ecologically important, as they can have great impact on host population dynamics and functioning of entire ecosystems. Nevertheless, little is known about their prevalence in aquatic habitats. Here, we investigate the diversity and distributional patterns of the protist parasites Perkinsus and Parvilucifera (Perkinsea). Our approach included 454 pyrosequencing of the 18S rDNA gene obtained from a high-altitude lake (Lake Finsevatn, Norway) and phylogenetic analyses of all publicly available sequences related to Perkinsea. The applied PCR primers target a 450 bp region that encompass the variable V4 region of the 18S rDNA gene and have been optimized for the Titanium upgrade of the 454 technology. Nearly 5000 sequences longer than 150 bp were recovered from nearly all eukaryotic supergroups, and of those, 13 unique sequences were affiliated to Perkinsea. Thus, our new strategy for 454 amplicon sequencing was able to recover a large diversity of distantly related eukaryotes and previously unknown species of Perkinsea. In addition, we identified 40 Perkinsea sequences in GenBank generated by other recent diversity surveys. Importantly, phylogenetic analyses of these sequences identified 17 habitat-specific marine and freshwater clades (PERK 1-17). Hence, only a few successful transitions between these habitats have taken place over the entire history of Perkinsea, suggesting that the boundary between marine and fresh waters may constitute a barrier to cross-colonizations for intracellular parasites.
Metagenome of the Mediterranean deep chlorophyll maximum studied by direct and fosmid library 454 pyrosequencing
Authors: Ghai Rohit , Martin-Cuadrado Ana-Belén , Molto Aitor Gonzaga , Heredia Inmaculada García , Cabrera Raúl , Martin Javier , Verdú Miguel , Deschamps Philippe , Moreira David , López-García Purificación , Mira Alex , Rodriguez-Valera Francisco
Published: April 2010

The deep chlorophyll maximum (DCM) is a zone of maximal photosynthetic activity, generally located toward the base of the photic zone in lakes and oceans. In the tropical waters, this is a permanent feature, but in the Mediterranean and other temperate waters, the DCM is a seasonal phenomenon. The metagenome from a single sample of a mature Mediterranean DCM community has been 454 pyrosequenced both directly and after cloning in fosmids. This study is the first to be carried out at this sequencing depth (ca. 600 Mb combining direct and fosmid sequencing) at any DCM. Our results indicate a microbial community massively dominated by the high-light-adapted Prochlorococcus marinus subsp. pastoris, Synechococcus sp., and the heterotroph Candidatus Pelagibacter. The sequences retrieved were remarkably similar to the existing genome of P. marinus subsp. pastoris with a nucleotide identity over 98%. Besides, we found a large number of cyanophages that could prey on this microbe, although sequence conservation was much lower. The high abundance of phage sequences in the cellular size fraction indicated a remarkably high proportion of cells suffering phage lytic attack. In addition, several fosmids clearly belonging to Group II Euryarchaeota were retrieved and recruited many fragments from the total direct DNA sequencing suggesting that this group might be quite abundant in this habitat. The comparison between the direct and fosmids sequencing revealed a bias in the fosmid libraries against low-GC DNA and specifically against the two most dominant members of the community, Candidatus Pelagibacter and P. marinus subsp. pastoris, thus unexpectedly providing a feasible method to obtain large genomic fragments from other less prevalent members of this community.
Widespread homologous recombination within and between Streptomyces species
Authors: Doroghazi James R , Buckley Daniel H
Published: April 2010

Horizontal gene transfer (HGT) is widespread in the microbial world, but its impact on the origin and persistence of microbial species remains poorly defined. HGT can result in either acquisition of new genetic material or homologous replacement of existing genes. The evolutionary significance of homologous recombination in a population can be quantified by examining the relative rates at which polymorphisms are introduced from recombination (ρ) and mutation (θw). We used multilocus sequence analysis (MLSA) to quantify both intraspecies and interspecies homologous recombination among streptomycetes, multicellular Gram-positive bacteria ubiquitous in soil, which are an important source of antibiotics and bioactive compounds. Intraspecies recombination was examined using strains of Streptomyces flavogriseus isolated from soils at five locations spanning 1000 km. The strains had >99.8% nucleotide identity across the loci examined. We found remarkable levels of gene exchange within S. flavogriseus (ρ/θw=27.9), and found that the population was in linkage equilibrium (standardized index of association=0.0018), providing evidence for a freely recombining sexual population structure. We also examined interspecies homologous recombination among different Streptomyces species in an MLSA data set and found that 40% of the species had housekeeping genes acquired through HGT. The recombination rate between these named species (ρ/θw=0.21) exceeds that observed within many species of bacteria. Despite widespread gene exchange in the genus, the intraspecies recombination rate exceeded the interspecies rate by two orders of magnitude suggesting that patterns of gene exchange and recombination may shape the evolution of streptomycetes.
Tradeoff between enzyme and metabolite efficiency maintains metabolic homeostasis upon perturbations in enzyme capacity
Authors: Fendt Sarah‐Maria , Buescher Joerg Martin , Rudroff Florian , Picotti Paola , Zamboni Nicola , Sauer Uwe
Published: April 2010

What is the relationship between enzymes and metabolites, the two major constituents of metabolic networks? We propose three alternative relationships between enzyme capacity and metabolite concentration alterations based on a Michaelis–Menten kinetic; that is enzyme capacities, metabolite concentrations, or both could limit the metabolic reaction rates. These relationships imply different correlations between changes in enzyme capacity and metabolite concentration, which we tested by quantifying metabolite, transcript, and enzyme abundances upon local (single‐enzyme modulation) and global (GCR2 transcription factor mutant) perturbations in Saccharomyces cerevisiae. Our results reveal an inverse relationship between fold‐changes in substrate metabolites and their catalyzing enzymes. These data provide evidence for the hypothesis that reaction rates are jointly limited by enzyme capacity and metabolite concentration. Hence, alteration in one network constituent can be efficiently buffered by converse alterations in the other constituent, implying a passive mechanism to maintain metabolic homeostasis upon perturbations in enzyme capacity.
Pre‐dispositions and epigenetic inheritance in the Escherichia coli lactose operon bistable switch
Authors: Robert Lydia , Paul Gregory , Chen Yong , Taddei François , Baigl Damien , Lindner Ariel B
Published: April 2010

The lactose operon regulation in Escherichia coli is a primary model of phenotypic switching, reminiscent of cell fate determination in higher organisms. Under conditions of bistability, an isogenic cell population partitions into two subpopulations, with the operon's genes turned on or remaining off. It is generally hypothesized that the final state of a cell depends solely on stochastic fluctuations of the network's protein concentrations, particularly on bursts of lactose permease expression. Nevertheless, the mechanisms underlying the cell switching decision are not fully understood. We designed a microfluidic system to follow the formation of a transiently bimodal population within growing microcolonies. The analysis of genealogy and cell history revealed the existence of pre‐disposing factors for switching that are epigenetically inherited. Both the pre‐induction expression stochasticity of the lactose operon repressor LacI and the cellular growth rate are predictive factors of the cell's response upon induction, with low LacI concentration and slow growth correlating with higher switching probability. Thus, stochasticity at the local level of the network and global physiology are synergistically involved in cell response determination.
Transcript counting in single cells reveals dynamics of rDNA transcription
Authors: Tan Rui Zhen , van Oudenaarden Alexander
Published: April 2010

Most eukaryotes contain many tandem repeats of ribosomal RNA genes of which only a subset is transcribed at any given time. Current biochemical methods allow for the determination of the fraction of transcribing repeats (ON) versus non‐transcribing repeats (OFF) but do not provide any dynamical information and obscure any transcription activity at the single‐cell level. Here, we use a fluorescence in situ hybridization (FISH) technique that allows the detection of single‐RNA molecules in individual yeast cells. We use this method complemented with theoretical modeling to determine the rate of switching from OFF to ON (activation rate) and the average number of RNA molecules produced during each transcriptional burst (burst size). We explore how these two variables change in mutants and different growth conditions, and show that this method resolves changes in these two variables even when the average rDNA expression is unaltered. These phenotypic changes could not have been detected by traditional biochemical assays.
Generation of Leptin Receptor Bone Marrow Chimeras: Recovery From Irradiation, Immune Cellularity, Cytokine Expression, and Metabolic Parameters
Authors: Gove Melissa E. , Sherry Christina L. , Pini Maria , Fantuzzi Giamila
Published: April 2010

Leptin regulates appetite and metabolism but also immunity and inflammation. Although functional leptin receptors (LepR) are expressed on hematopoietic cells, the role of these receptors in regulating immune function in vivo remains controversial. To clarify this issue, we performed bone marrow (BM) transplantation between obese db/db mice, lacking LepR, and wild‐type (WT) mice. Results indicate that expression of LepR on BM‐derived cells directly, though partially, regulates spleen and thymus cellularity, although the environment of db mice contributes to maintaining reduced cellularity of these organs. Selective expression of LepR on BM‐derived cells also modulates leptin and adiponectin levels, with induction of a more favorable adipokine environment in the WT→db/db group. However, LepR signaling in BM‐derived cells is not involved in regulation of body weight (BW) and composition, glycemia, hepatosteatosis or adipose tissue inflammation, although it modulates expression of interleukin (IL)‐1β in the brain. Finally, data indicate that db mice have an increased susceptibility to irradiation compared to WT mice in terms of BW loss and recovery of leukocyte counts in peripheral blood. Therefore, interpretation of results obtained using BM chimeras between WT and db mice should take into account the difference in radiation sensitivity between the two types of animals.
Body Fat Distribution and Inflammation Among Obese Older Adults With and Without Metabolic Syndrome
Authors: Koster Annemarie , Stenholm Sari , Alley Dawn E. , Kim Lauren J. , Simonsick Eleanor M. , Kanaya Alka M. , Visser Marjolein , Houston Denise K. , Nicklas Barbara J. , Tylavsky Frances A. , Satterfield Suzanne , Goodpaster Bret H. , Ferrucci Luigi , Harris Tamara B. ,   For the Health ABC Study
Published: April 2010

The protective mechanisms by which some obese individuals escape the detrimental metabolic consequences of obesity are not understood. This study examined differences in body fat distribution and adipocytokines in obese older persons with and without metabolic syndrome. Additionally, we examined whether adipocytokines mediate the association between body fat distribution and metabolic syndrome. Data were from 729 obese men and women (BMI ≥30 kg/m2), aged 70–79 participating in the Health, Aging and Body Composition (Health ABC) study. Thirty‐one percent of these obese men and women did not have metabolic syndrome. Obese persons with metabolic syndrome had significantly more abdominal visceral fat (men: P = 0.04; women: P < 0.01) and less thigh subcutaneous fat (men: P = 0.09; women: P < 0.01) than those without metabolic syndrome. Additionally, those with metabolic syndrome had significantly higher levels of interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), and plasminogen activator inhibitor‐1 (PAI‐1) than individuals without metabolic syndrome. Per standard deviation higher in visceral fat, the likelihood of metabolic syndrome significantly increased in women (odds ratio (OR): 2.16, 95% confidence interval (CI): 1.59–2.94). In contrast, the likelihood of metabolic syndrome decreased in both men (OR: 0.56, 95% CI: 0.39–0.80) and women (OR: 0.49, 95% CI: 0.34–0.69) with each standard deviation higher in thigh subcutaneous fat. These associations were partly mediated by adipocytokines; the association between thigh subcutaneous fat and metabolic syndrome was no longer significant in men. In summary, metabolically healthy obese older persons had a more favorable fat distribution, characterized by lower visceral fat and greater thigh subcutaneous fat and a more favorable inflammatory profile compared to their metabolically unhealthy obese counterparts.
Increased Whole‐Body Adiposity Without a Concomitant Increase in Liver Fat is Not Associated With Augmented Metabolic Dysfunction
Authors: Magkos Faidon , Fabbrini Elisa , Mohammed B. Selma , Patterson Bruce W. , Klein Samuel
Published: April 2010

Aim of this study was to determine whether an increase in adiposity, without a concomitant increase in intrahepatic triglyceride (IHTG) content, is associated with a deterioration in metabolic function. To this end, multiorgan insulin sensitivity, assessed by using a two‐stage hyperinsulinemic–euglycemic clamp procedure in conjunction with stable isotopically labeled tracer infusion, and very low‐density lipoprotein (VLDL) kinetics, assessed by using stable isotopically labeled tracer infusion and mathematical modeling, were determined in 10 subjects with class I obesity (BMI: 31.6 ± 0.3 kg/m2; 37 ± 2% body fat; visceral adipose tissue (VAT): 1,225 ± 144 cm3) and 10 subjects with class III obesity (BMI: 41.5 ± 0.5 kg/m2; 43 ± 2% body fat; VAT: 2,121 ± 378 cm3), matched on age, sex, and IHTG content (14 ± 4 and 14 ± 3%, respectively). No differences between class I and class III obese groups were detected in insulin‐mediated suppression of palmitate (67 ± 3 and 65 ± 3%, respectively; P = 0.635) and glucose (67 ± 3 and 73 ± 5%, respectively; P = 0.348) rates of appearance in plasma, and the insulin‐mediated increase in glucose disposal (218 ± 18 and 193 ± 30%, respectively; P = 0.489). In addition, no differences between class I and class III obese groups were detected in secretion rates of VLDL‐triglyceride (6.5 ± 1.0 and 6.0 ± 1.4 µmol/l·min, respectively; P = 0.787) and VLDL‐apolipoprotein B‐100 (0.40 ± 0.05 and 0.41 ± 0.04 nmol/l·min, respectively; P = 0.866), and plasma clearance rates of VLDL‐triglyceride (31 (16–59) and 29 (18–46) ml/min, respectively; P = 0.888) and VLDL‐apolipoprotein B‐100 (15 (11–19) and 17 (11–25) ml/min, respectively; P = 0.608). We conclude that increased adiposity without a concomitant increase in IHTG content does not cause additional abnormalities in adipose tissue, skeletal muscle, and hepatic insulin sensitivity, or VLDL metabolism.