bluuebunny/crossref_metadata_2025 huggingface dataset:
Prehypertension and Cardiovascular Disease Risk in the Women’s Health Initiative
Authors: Hsia Judith , Margolis Karen L. , Eaton Charles B. , Wenger Nanette K. , Allison Matthew , Wu LieLing , LaCroix Andrea Z. , Black Henry R.
Published: February 2007

Background—

Prehypertension is common and is associated with increased vascular mortality. The extent to which it increases risk of nonfatal myocardial infarction, stroke, and congestive heart failure is less clear.

Methods and Results—

We determined the prevalence of prehypertension, its association with other coronary risk factors, and the risk for incident cardiovascular disease events in 60 785 postmenopausal women during 7.7 years of follow-up using Cox regression models that included covariates as time-dependent variables. Prehypertension was present at baseline in 39.5%, 32.1%, 42.6%, 38.7%, and 40.3% of white, black, Hispanic, American Indian, and Asian women, respectively (
P
<0.0001 across ethnic groups). Age, body mass index, and prevalence of diabetes mellitus and hypercholesterolemia increased across blood pressure categories, whereas smoking decreased (all
P
<0.0001). Compared with normotensive women (referent), adjusted hazard ratios for women with prehypertension were 1.58 (95% confidence interval [CI], 1.12 to 2.21) for cardiovascular death, 1.76 (95% CI, 1.40 to 2.22) for myocardial infarction, 1.93 (95% CI, 1.49 to 2.50) for stroke, 1.36 (95% CI, 1.05 to 1.77) for hospitalized heart failure, and 1.66 (95% CI, 1.44 to 1.92) for any cardiovascular event. Hazard ratios for the composite outcome with prehypertension did not differ between ethnic groups (
P
=0.71 for interaction), although the numbers of events among Hispanic and Asian women were small.

Conclusions—

Prehypertension is common and was associated with increased risk of myocardial infarction, stroke, heart failure, and cardiovascular death in white and nonwhite postmenopausal women. Risk factor clustering was conspicuous, emphasizing the need for trials evaluating the efficacy of global cardiovascular risk reduction through primordial prevention.
Gender Differences in Hospital Mortality and Use of Percutaneous Coronary Intervention in Acute Myocardial Infarction
Authors: Milcent Carine , Dormont Brigitte , Durand-Zaleski Isabelle , Steg Philippe Gabriel
Published: February 2007

Background—

Women with acute myocardial infarction have a higher hospital mortality rate than men. This difference has been ascribed to their older age, more frequent comorbidities, and less frequent use of revascularization. The aim of this study is to assess these factors in relation to excess mortality in women.

Methods and Results—

All hospital admissions in France with a discharge diagnosis of acute myocardial infarction were extracted from the national payment database. Logistic regression on mortality was performed for age, comorbidities, and coronary interventions. Nonparametric microsimulation models estimated the percutaneous coronary intervention and mortality rates that women would experience if they were “treated like men.” Data were analyzed from 74 389 patients hospitalized with acute myocardial infarction, 30.0% of whom were women. Women were older (75 versus 63 years of age;
P
<0.001) and had a higher rate of hospital mortality (14.8% versus 6.1%;
P
<0.0001) than men. Percutaneous coronary interventions were more frequent in men (7.4% versus 4.8%; 24.4% versus 14.2% with stent;
P
<0.001). Mortality adjusted for age and comorbidities was higher in women (
P
<0.001), with an excess adjusted absolute mortality of 1.95%. Simulation models related 0.46% of this excess to reduced use of procedures. Survival benefit related to percutaneous coronary intervention was lower among women.

Conclusions—

The difference in mortality rate between men and women with acute myocardial infarction is due largely to the different age structure of these populations. However, age-adjusted hospital mortality was higher for women and was associated with a lower rate of percutaneous coronary intervention. Simulations suggest that women would derive benefit from more frequent use of percutaneous coronary intervention, although these procedures appear less protective in women than in men.
The Effect of Lower Stratospheric Shear on Baroclinic Instability
Authors: Wittman Matthew A. H. , Charlton Andrew J. , Polvani Lorenzo M.
Published: February 2007

Using a hierarchy of models, and observations, the effect of vertical shear in the lower stratosphere on baroclinic instability in the tropospheric midlatitude jet is examined. It is found that increasing stratospheric shear increases the phase speed of growing baroclinic waves, increases the growth rate of modes with low synoptic wavenumbers, and decreases the growth rate of modes with higher wavenumbers. The meridional structure of the linear modes, and their acceleration of the zonal mean jet, changes with increasing stratospheric shear, but in a way that apparently contradicts the observed stratosphere–troposphere northern annular mode (NAM) connection. This contradiction is resolved at finite amplitude. In nonlinear life cycle experiments it is found that increasing stratospheric shear, without changing the jet structure in the troposphere, produces a transition from anticyclonic (LC1) to cyclonic (LC2) behavior at wavenumber 7. All life cycles with wavenumbers lower than 7 are LC1, and all with wavenumber greater than 7 are LC2. For the LC1 life cycles, the effect of increasing stratospheric shear is to increase the poleward displacement of the zonal mean jet by the eddies, which is consistent with the observed stratosphere–troposphere NAM connection. Finally, it is found that the connection between high stratospheric shear and high-tropospheric NAM is present by NCEP–NCAR reanalysis data.
A Simple Model of the Millimeter-Wave Scattering Parameters of Randomly Oriented Aggregates of Finite Cylindrical Ice Hydrometeors
Authors: Weinman J. A. , Kim M-J.
Published: February 2007

Spaceborne millimeter-wave radiometric measurements offer the potential to observe snowfall at high latitudes. A spaceborne W-band cloud radar on CloudSat has been able to observe snow. There is thus a need for a relatively simple representation of millimeter-wave scattering parameters of snow that can be incorporated into algorithms to retrieve snowfall from remotely sensed millimeter-wave brightness temperature measurements and for computing the millimeter-wave backscatter phase function of randomly oriented aggregates of ice prisms or columns.

The extinction coefficients, asymmetry factors, and backscatter phase functions describing scattering by randomly oriented aggregates of elongated cylinders were computed from the discrete dipole approximation. These parameters were also computed by means of a T-matrix model applied to single blunt cylinders by employing a phase delay that only depended on the frequency and the ratio of the volume to the projected area of the cylindrical aggregates. These scattering parameters were fitted by empirical analytical functions that only depended on that phase delay. This permitted consideration of numerous aggregate shapes with far less computational effort than that required by the discrete dipole approximation.

The results of this analysis were applied to measurements of millimeter-wave extinction, radar reflectivity, and snow size distributions obtained during the SNOW-TWO field experiment conducted by the U.S. Army in 1984. Although the simultaneity of the various measurements was not well documented, the theoretical results fell within the range of measurement uncertainty. Model results of the extinction coefficient and asymmetry factor needed to compute 183-GHz brightness temperatures measured by the NOAA Advanced Microwave Sounding Unit-B (AMSU-B) radiometers are presented in the appendix.
On the Definition of the Cloud Water Content Fluctuations and Its Effects on the Computation of a Second-Order Liquid Water Correlation
Authors: Bouzereau E. , Musson-Genon L. , Carissimo B.
Published: February 2007

In subgrid-scale condensation schemes of cloud models, the majority of previous authors have relied on results presented in a paper by Bougeault. In the present paper, second-order liquid water correlations are restated that differ from the former paper but are coherent with the corrigendum of Mellor. These differences are explained here through two different underlying definitions of cloud water content fluctuations; they can be summarized by whether or not unsaturated air within a grid box contributes to the eddy flux of the cloud water content. Taking into account the issue mentioned above, the “buoyancy flux” is also derived. Although the full impact of these changes has not been evaluated here, it may become important for future global cloud-resolving climate models.
On Boundary Layer Separation in the Lee of Mesoscale Topography
Authors: Jiang Qingfang , Doyle James D. , Wang Shouping , Smith Ronald B.
Published: February 2007

The onset of boundary layer separation (BLS) forced by gravity waves in the lee of mesoscale topography is investigated based on a series of numerical simulations and analytical formulations. It is demonstrated that BLS forced by trapped waves is governed by a normalized ratio of the vertical velocity maximum to the surface wind speed; other factors such as the mountain height, mountain slope, or the leeside speedup factor are less relevant. The onset of BLS is sensitive to the surface sensible heat flux—a positive heat flux tends to increase the surface wind speed through enhancing the vertical momentum mixing and accordingly inhibits the occurrence of BLS, and a negative heat flux does the opposite. The wave forcing required to cause BLS decreases with an increase of the aerodynamical roughness zo; a larger zo generates larger surface stress and weaker surface winds and therefore promotes BLS. In addition, BLS shows some sensitivity to the terrain geometry, which modulates the wave characteristics. For a wider ridge, a higher mountain is required to generate trapped waves with a wave amplitude comparable to that generated by a lower but narrower ridge. The stronger hydrostatic waves associated with the wider and higher ridge play only a minor role in the onset of BLS.

It has been demonstrated that although hydrostatic waves generally do not directly induce BLS, undular bores may form associated with wave breaking in the lower troposphere, which in turn induce BLS. In addition, BLS could occur underneath undular jump heads or associate with trapped waves downstream of a jump head in the presence of a low-level inversion.
Intraseasonal Variability of the Zonal-Mean Extratropical Tropopause Height
Authors: Son Seok-Woo , Lee Sukyoung , Feldstein Steven B.
Published: February 2007

The physical processes that drive the fluctuations of the extratropical tropopause height are examined with the National Centers for Environmental Prediction–National Center for Atmospheric Research (NCEP–NCAR) reanalysis data.

A composite zonal-mean heat budget analysis for the Northern Hemisphere winter shows that fluctuations in the extratropical tropopause height result not only from a warming of the troposphere but also from an even stronger cooling of the lower stratosphere. While the tropospheric warming is caused by a poleward eddy heat transport associated with baroclinic eddies, the stratospheric cooling is driven primarily by planetary-scale waves. The results from analyses of synoptic- and planetary-scale eddy kinetic energy and Eliassen–Palm fluxes are consistent with the planetary waves first gaining their energy within the troposphere, and then propagating vertically into the stratosphere.

For the Southern Hemisphere, while lower-stratospheric temperature anomalies still play an important role for the fluctuations in the tropopause height, the temperature anomalies are accounted for primarily by a poleward eddy heat transport associated with synoptic-scale eddies, and by diabatic heating.

These results indicate that, although the height of the extratropical tropopause is modulated by baroclinic eddies, which is consistent with existing theories, the amount of the modulation is highly influenced by stratospheric processes.
Sodar Measurements of Wing Vortex Strength and Position
Authors: Bradley Stuart , Mursch-Radlgruber Erich , von Hünerbein Sabine
Published: February 2007

A method is developed for robust real-time visualization of aircraft vortex spatial and temporal development based on measurement data from a line array of sodars. The method relies on using a potential-flow vortex model, with spatial averaging according to the along-beam and transverse spatial resolution of the sodar. The model comprises the wing vortex pair, together with two image vortices below ground such that there is no flow through the ground surface. An analytic solution for the temporal–spatial evolution of this four-vortex system is obtained as an aid to establishing relevant scales and performance criteria for any sodar. Field results from an array of four sodars are used on an individual profile basis (every 2 s of real time) to fit the model parameters of vortex circulation, position, and spacing. This method gives vortex trajectories and strength as a function of real time without dependence on assumptions regarding interactions with the atmosphere. Estimates of parameter uncertainties are also produced in real time, and it is found that estimates of position and spacing can be obtained to around ±4 m and of vortex circulation to ±50 m2 s−1. Recommendations are given for optimizing sodars for vortex measurements using practical technology.
Is Friendship Consistent with Competitive Market Exchange?
Authors: Dulsrud Arne , Grønhaug Kjell
Published: February 2007

A conventional assumption within sociology of markets is that social ties are crucial in economic life, but that too strong relationships between sellers and buyers can create role conflicts and restrict business. Using qualitative interviews with Norwegian exporters and Danish importers, this article examines transactions in the international fish trade. We find that the assumed episodic and highly competitive commodity trade is rooted in dyadic networks and personal trust; inspired by the work of Goffman, we analyse transaction patterns as ‘interaction order’. The transaction pattern is dependent on a particular organization of social interaction, interaction in which business dealings are divided into delimited spheres of the ‘formal’, ‘personal’ and ‘private’. This division reflects a differentiation of the social roles, one in which traders avoid the role conflicts inherent in close relationships. We conclude by stating that economic sociology should probably be less preoccupied with formal network configurations and instead be focused more on how actors actually use social ties in the marketplace to conduct business, and on how these ties are linked to price mechanisms.
Communities, Places, and Social Networks
Authors: Piselli Fortunata
Published: February 2007

This article analyzes the concept of community using the network analysis perspective. In opposition to classical studies (sociological and anthropological) that identify communities with particular residential units, it is necessary to study a community as a network of relations rather than as a spatially defined unit. The community is not a “place” but a network of meaningful social relations with friends, neighbors, relatives, and work colleagues who do not necessarily belong to the same residential unit. This article analyzes personal relations and various forms of communication and exchange that take place in different ambits and argues that community studies must be approached from a network analytic perspective. Although social and spatial dimensions may condition and reinforce each other, communities are not places that can be circumscribed spatially. Rather than the spatial dimension, social networks integrate and separate, defining exclusion from or inclusion in particular domains.
Ecologies of Innovation
Authors: Adkins Barbara , Foth Marcus , Summerville Jennifer , Higgs Peter L.
Published: February 2007

Research on creative-industries clusters emphasizes both community and network dynamics in cross-organizational linkages and their role in fostering group and individual creativity and innovation. This article turns to an economic sociology framework, examining what is at stake in these collaborations and their embeddedness in broader social relationships. The authors report on a qualitative study of the linking and networking practices and rationales of the design sector collocated in an inner-city area in Brisbane, Australia. The study suggests that not only was the locale important in both community and network-level relationships but also that these should be understood in relation to symbolic representation in the field of design. The article argues that the innovative potential of interorganizational linkages should be understood in terms of layers of symbolic identifications at the level of the field of design, the symbolic community associated with the locale, and the “awareness space” of networks.
The Way We Do Things Around Here
Authors: Francisco Scott
Published: February 2007

Buildings have always played a role in negotiating the boundary between individual expression and social context. Through the lens of architectural history, this article explores the relationships between “community,” “culture,” “craft,” and “specification”—concepts fundamental to the way people express themselves and develop group behaviors and collective meaning. The article focuses on the tension between “craft,” as an implicit community practice based on “skill” and “knowledge,” and “specification,” which presumes an explicit and abstract means of communicating “information.” At the center is the elusive concept of “design.” But what is design? How does it affect culture at an incremental and substantial level? How do new values, both individual and collective, weigh in to the question of cultural change through design? Coming full circle, the article reflects on how the design of built space is integrated into communicative praxis itself, framing and cultivating particular forms of dialogue while displacing or resisting others.
Towards a critical theory of whiteness
Authors: Owen David S.
Published: February 2007

In this article I argue that a critical theory of whiteness is necessary, though not sufficient, to the formulation of an adequate explanatory account of the mechanisms of racial oppression in the modern world. In order to explain how whiteness underwrites systems of racial oppression and how it is reproduced, the central functional properties of whiteness are identified. I propose that understanding whiteness as a structuring property of racialized social systems best explains these functional properties. Given the variety of conceptions of whiteness in the literature, the several uses of the term are analysed and it is shown that there is a unifying concept underlying these various senses of whiteness. Lastly, some of the implications of this account of whiteness for anti-racist engagement are considered.
Becoming Who You Are
Authors: Metcalfe Andrew , Game Ann
Published: February 2007

Desirous time is not conducive to learning because its fantasies are distractions from the present moment, the time when genuine creative possibilities emerge. In contrast, the time of love, of an I–Thou relation, is the time of potential and infinitude. This is when engaged learning occurs, and when students develop the practices that open them to a creative way of being. In contrast to the future-oriented linearity of desirous time, the time of creative learning is the time of presence. This argument is developed using interview material from well-known Australians and well-regarded Australian teachers.
Effects of Gender and Age on Retrospective Time Judgements
Authors: Brañas-Garza Pablo , Espinosa-Fernández Lourdes , Serrano-del-Rosal Rafael
Published: February 2007

This study provides additional empirical evidence for research concerning the effects of gender and age on retrospective time judgements using data obtained from a Spanish database with more than 40,000 individual observations on time estimations. Statistical analyses were performed using the Levene F-test and the t-test of variances and means, respectively. The most important results of the study are as follows: (a) differences in time estimation in relation to gender largely depend on the age groups analysed, with greater differences observed in the younger age group; and (b) although there are some differences regarding age, they are related to certain age groups, particularly the youngest age group.
Marked by Visibility of Psoriasis in Everyday Life
Authors: Uttjek Margaretha , Nygren Lennart , Stenberg Berndt , Dufåker Mona
Published: February 2007

In this study, the authors aimed at a sociological approach to the individual’s everyday life with psoriasis and to this end conducted qualitative interviews with 18 persons from a county in northern Sweden. The most difficult aspects of living with psoriasis were being marked by the visibility of psoriasis, especially in the younger ages, and the visibility of joint changes. Therefore, those with both rashes and joint changes felt marked and discredited in a twofold way. Commonly used coping strategies were routinization of both the treatment and the adjustment to the marking process, and acceptance, and these strategies developed with age. Most participants experienced a good quality of life but still could find nothing positive about psoriasis. The authors suggest efforts toward increased awareness among health care professionals of the marking process and future qualitative studies about experiences of psoriasis during adolescence.
Community Police and Youth Programs as a Context for Positive Youth Development
Authors: Anderson Stephen A. , Sabatelli Ronald M. , Trachtenberg Jennifer
Published: February 2007

The results of an evaluation of community police youth development programs are presented. Youth involved in Police Working With Youth Programs were contrasted with youth recruited from local high schools. It was hypothesized that youth who participate in police programs would show more positive changes than youth in the comparison group in four general categories of youth outcomes. The outcomes included indicators of youth personal adjustment, social competencies, positive adult-youth connections, and positive youth-community connections. Analyses of the total sample of youth who participated in the programs indicated no significant changes. However, a subgroup of youth who entered the programs with low levels of psychosocial functioning showed significantly more positive changes than the comparison group on several of the outcomes studied. These included self-assertive efficacy, self-regulatory efficacy, and empathy for others. The vast majority of youth found participating in Police Working With Youth Programs to be a very positive experience.
Acute lower limb ischemia due to thrombo-embolic arterial occlusions in two previously healthy men with markedly elevated Lp(a)
Authors: Bedarida Gabriella V , Hoffmann Ulrich , Tatò Federico
Published: February 2007

Lipoprotein (a) (Lp(a)) is a well-documented risk factor for atherosclerotic cardiovascular disease. Its role in acute thrombo-embolic occlusions of peripheral arteries is not known. We describe two cases of multiple, acute, peripheral arterial occlusions in two previously healthy men with markedly elevated Lp(a). Both cases had unsatisfactory results after percutaneous and surgical revascularization procedures. Experience yielded in these two cases suggests that when an unfavorable out-come occurs in a peripheral artery disease patient in the absence of the regular risk factors, Lp(a) should be determined and its role investigated.
Stitch'nBitch
Authors: Minahan Stella , Cox Julie Wolfram
Published: February 2007

We discuss the emergence of a new craft movement known as Stitch'nBitch. Prevalent around the globe, particularly among women, this movement is based locally in places such as hotels and cafes, and virtually using the internet. The women meet to knit, stitch and talk. The groups use new technologies as an enabler and resource exchange. At the same time, their presence can be seen, in part, as a negative response to major political, social and technological changes including globalization, terrorism, damage to the environment and the dislocation of the Information Society. We introduce five themes to assist in the development of a research agenda into this new form of material culture, discussing (1) remedial, (2) progressive, (3) resistance, (4) nostalgic and (5) ironic possibilities. Each is considered in terms of their respective foci on community, cyberfeminism, craft, conservation and comment.
Particularism and Reasons: A Reply to Kirchin
Authors: Norman Richard
Published: February 2007

Valency switching can appear especially puzzling if we think of moral reasons as ‘pushes and pulls’—considerations whose job it is to get us to act or to stop us acting. Talk of ‘default valency’ doesn't remove the puzzle, it merely restates it. We need a different picture of reasons—perhaps as providing a map of the moral terrain which helps us to see which actions are appropriate to which situations, and who the appropriate agents are. The role of virtue concepts in particular is more complex and varied than that of providing ‘reasons for acting’. A more holistic picture of reasons can make valency switching less mysterious.
Defending the Right
Authors: Dancy Jonathan
Published: February 2007

In this paper I consider what might be my best response to various difficulties and challenges that emerged at a conference held at the University of Kent in December 2004, the contributions to which are given in the same volume. I comment on Crisp's distinction between ultimate and non-ultimate reasons, and reply to McKeever and Ridge on default reasons, and to Norman on the idea of a reason for action. I don't here consider what other particularists might want to say; I certainly don't think that my way of doing these things is the only possible one, but not surprisingly I am interested in seeing what resources it might have to defend itself.
Childhood asthma and fruit consumption
Authors: Okoko B. J. , Burney P. G. , Newson R. B. , Potts J. F. , Shaheen S. O.
Published: February 2007

The present authors investigated whether wheezing is less common in children who consume more apples and other fruits.

A population-based survey of 2,640 primary school children aged 5–10 yrs was carried out in Greenwich (South London, UK). Information about asthma symptoms and fruit consumption was obtained by means of a questionnaire.

After controlling for potential confounding variables, eating bananas at least once a day (compared with less than once a month) was negatively associated with current wheeze (odds ratio 0.66; 95% confidence interval 0.44–1.00) and ever wheeze (0.69 (0.50–0.95)), but not with ever asthma (0.80 (0.56–1.14)). Drinking apple juice from concentrate at least once a day (compared with less than once a month) was also negatively associated with current wheeze (0.53 (0.34–0.83)), weakly associated with ever wheeze (0.74 (-0.54–1.02)), but not associated with ever asthma. Consumption of apples, other fruits and orange juice was not significantly associated with asthma symptoms.

No association was found between eating fresh apples and asthma symptoms in the study population, but some evidence was found to suggest that a higher consumption of apple juice from concentrate and bananas may protect against wheezing in children.
Macrolides, quinolones and amoxicillin/clavulanate for chronic bronchitis: a meta-analysis
Authors: Siempos I. I. , Dimopoulos G. , Korbila I. P. , Manta K. , Falagas M. E.
Published: February 2007

The comparative effectiveness and safety of macrolides, quinolones and amoxicillin/clavulanate (A/C) for the treatment of patients with acute bacterial exacerbation of chronic bronchitis (ABECB) was evaluated in the present study.

PubMed, Current Contents and the Cochrane Central Register of Controlled Trials were searched to identify relevant randomised controlled trials (RCTs).

In total, 19 RCTs (20 comparisons) were included in the present analysis. There was no difference regarding treatment success in intention-to-treat and clinically evaluable patients between macrolides and quinolones, A/C and quinolones or A/C and macrolides. The treatment success in microbiologically evaluable patients was lower for macrolides compared with quinolones (odds ratio (OR) 0.47, 95% confidence interval (CI) 0.31–0.69). Fewer quinolone-recipients experienced a recurrence of ABECB after resolution of the initial episode compared with macrolide-recipients during the 26-week period following therapy. Adverse effects in general were similar between macrolides and quinolones. Administration of A/C was associated with more adverse effects (mainly diarrhoea) than quinolones (OR 1.36, 95% CI 1.01–1.85).

Macrolides, quinolones and amoxicillin/clavulanate may be considered equivalent for the treatment of patients with an acute bacterial exacerbation of chronic bronchitis in terms of short-term effectiveness. Quinolones are associated with better microbiological success and fewer recurrences of acute bacterial exacerbation of chronic bronchitis than macrolides, while amoxicillin/clavulanate is associated with more adverse effects than both comparators.
Inhibition of PDGF, VEGF and FGF signalling attenuates fibrosis
Authors: Chaudhary N. I. , Roth G. J. , Hilberg F. , Müller-Quernheim J. , Prasse A. , Zissel G. , Schnapp A. , Park J. E.
Published: February 2007

BIBF 1000 is a small molecule inhibitor targeting the receptor kinases of platelet-derived growth factor (PDGF), basic fibroblast growth factor and vascular endothelial growth factor, which have known roles in the pathogenesis of pulmonary fibrosis.

The anti-fibrotic potential of BIBF 1000 was determined in a rat model of bleomycin-induced lung fibrosis and in anex vivofibroblast differentiation assay. Rats exposed to a single intra-tracheal injection of bleomycin were treated with BIBF 1000 starting 10 days after bleomycin administration. To gauge for anti-fibrotic activity, collagen deposition and pro-fibrotic growth factor gene expression was analysed in isolated lungs. Furthermore, the activity of BIBF 1000 was compared with imatinib mesylate (combined PDGF receptor, c-kit and c-abl kinase inhibitor) and SB-431542 (transforming growth factor (TGF)-β receptor I kinase inhibitor) in anex vivoTGF-β-driven fibroblast to myofibroblast differentiation assay, performed in primary human bronchial fibroblasts.

Treatment of rats with BIBF 1000 resulted in the attenuation of fibrosis as assessed by the reduction of collagen deposition and the inhibition of pro-fibrotic gene expression. In the cellular assay both SB-431542 and BIBF 1000 showed dose-dependent inhibition of TGF-β-induced differentiation, whereas imatinib mesylate was inactive.

BIBF 1000, or related small molecules with a similar kinase inhibition profile, may represent a novel therapeutic approach for the treatment of idiopathic pulmonary fibrosis.
In silico identification of NF-kappaB-regulated genes in pancreatic beta-cells
Authors: Naamane Najib , van Helden Jacques , Eizirik Decio L
Published: February 2007

Background

Pancreatic beta-cells are the target of an autoimmune attack in type 1 diabetes mellitus (T1DM). This is mediated in part by cytokines, such as interleukin (IL)-1β and interferon (IFN)-γ. These cytokines modify the expression of hundreds of genes, leading to beta-cell dysfunction and death by apoptosis. Several of these cytokine-induced genes are potentially regulated by the IL-1β-activated transcription factor (TF) nuclear factor (NF)-κB, and previous studies by our group have shown that cytokine-induced NF-κB activation is pro-apoptotic in beta-cells. To identify NF-κB-regulated gene networks in beta-cells we presently used a discriminant analysis-based approach to predict NF-κB responding genes on the basis of putative regulatory elements.

Results

The performance of linear and quadratic discriminant analysis (LDA, QDA) in identifying NF-κB-responding genes was examined on a dataset of 240 positive and negative examples of NF-κB regulation, using stratified cross-validation with an internal leave-one-out cross-validation (LOOCV) loop for automated feature selection and noise reduction. LDA performed slightly better than QDA, achieving 61% sensitivity, 91% specificity and 87% positive predictive value, and allowing the identification of 231, 251 and 580 NF-κB putative target genes in insulin-producing INS-1E cells, primary rat beta-cells and human pancreatic islets, respectively. Predicted NF-κB targets had a significant enrichment in genes regulated by cytokines (IL-1β or IL-1β + IFN-γ) and double stranded RNA (dsRNA), as compared to genes not regulated by these NF-κB-dependent stimuli. We increased the confidence of the predictions by selecting only evolutionary stable genes, i.e. genes with homologs predicted as NF-κB targets in rat, mouse, human and chimpanzee.

Conclusion

The presentin silicoanalysis allowed us to identify novel regulatory targets of NF-κB using a supervised classification method based on putative binding motifs. This provides new insights into the gene networks regulating cytokine-induced beta-cell dysfunction and death.
Rapid evolution in response to introduced predators II: the contribution of adaptive plasticity
Authors: Latta Leigh C , Bakelar Jeremy W , Knapp Roland A , Pfrender Michael E
Published: February 2007

Background

Introductions of non-native species can significantly alter the selective environment for populations of native species, which can respond through phenotypic plasticity or genetic adaptation. We examined phenotypic and genetic responses ofDaphniapopulations to recent introductions of non-native fish to assess the relative roles of phenotypic plasticity versus genetic change in causing the observed patterns. TheDaphniacommunity in alpine lakes throughout the Sierra Nevada of California (USA) is ideally suited for investigation of rapid adaptive evolution because there are multiple lakes with and without introduced fish predators. We conducted common-garden experiments involving presence or absence of chemical cues produced by fish and measured morphological and life-history traits inDaphnia melanicapopulations collected from lakes with contrasting fish stocking histories. The experiment allowed us to assess the degree of population differentiation due to fish predation and examine the contribution of adaptive plasticity in the response to predator introduction.

Results

Our results show reductions in egg number and body size ofD. melanicain response to introduced fish. These phenotypic changes have a genetic basis but are partly due to a direct response to chemical cues from fish via adaptive phenotypic plasticity. Body size showed the largest phenotypic change, on the order of nine phenotypic standard deviations, with approximately 11% of the change explained by adaptive plasticity. Both evolutionary and plastic changes in body size and egg number occurred but no changes in the timing of reproduction were observed.

Conclusion

NativeDaphniapopulations exposed to chemical cues produced by salmonid fish predators display adaptive plasticity for body size and fecundity. The magnitude of adaptive plasticity was insufficient to explain the total phenotypic change, so the realized change in phenotypic means in populations exposed to introduced fish may be the result of a combination of initial plasticity and subsequent genetic adaptation. Our results suggest that immediately following the introduction of fish predators, adaptive plasticity may reduce the impact of selection through "Baldwin/Bogert effects" by facilitating the movement of populations toward new fitness optima. Our study of the response of a native species to an introduced predator enhances our understanding of the conditions necessary for rapid adaptive evolution and the relationship between rapid evolution and adaptive phenotypic plasticity.
Quality or equality? The Norwegian experience with medical monopolies
Authors: Rasmussen Knut , Bratlid Dag
Published: February 2007

Background

In order to maintain both quality and efficiency of health services in a small country with a scattered population, Norway established a monopoly system for 38 highly specialized medical services. The geographical distributions of these services, which are provided by one or two university hospitals only, were analysed.

Methods

The counties of residence for 2 711 patients admitted for the first time in 2001 to these 31 monopolies and 7 duopolies were identified.

Results

The general tendency observed was that with increasing distance from residential home to monopoly hospitals there was a declining coverage of these health services. The same pattern was found even with regard to explicit diagnoses or treatments such as organ transplantations (except renal transplantations). Duopolies seemed to yield a more even geographical distribution of the services.

Conclusion

Monopolies may serve as a useful means for maintaining quality in highly specialized medical services, but seem to have an inherent tendency to do this at the expense of geographical equality.
Achieving a high coverage – the challenge of controlling HIV spread in heroin users
Authors: Li Ming-qiang , Lee Shui-shan , Gan Zhi-gao , Tan Yi , Meng Jin-Huai , He Ming-liang
Published: February 2007

In China, the national plan to open 1000 methadone clinics over a five-year period provides a unique opportunity to assess the impacts of harm reduction in a country with concentrated HIV epidemic amongst heroin users. To track the progress of this public health response, data were collected from the first methadone clinic in Liuzhou, Guangxi, a province with a high HIV prevalence. In the first 15 months of its operation, a cumulative total of 488 heroin users, 86% of which male, had joined the programme. The first dose of methadone was given efficiently at a median of 2 days after registration. Of the 240 heroin users attending the clinic in August 2006, 61% took methadone for four days or more each week. The number of active methadone users, however, leveled off at around 170 after the first two months, despite the availability of capacity to deliver more services. The reasons for this observation are: firstly, the provision of one single service that may not be convenient to all heroin users; and secondly, concerns of heroin users who may feel insecure to come forward. As broad coverage is essential in ultimately reducing HIV risk, a low threshold approach is crucial, which should be supported by the removal of social obstacles and a refinement of the administrative procedures.
Health sector reforms and human resources for health in Uganda and Bangladesh: mechanisms of effect
Authors: Ssengooba Freddie , Rahman Syed Azizur , Hongoro Charles , Rutebemberwa Elizeus , Mustafa Ahmed , Kielmann Tara , McPake Barbara
Published: February 2007

Background

Despite the expanding literature on how reforms may affect health workers and which reactions they may provoke, little research has been conducted on the mechanisms of effect through which health sector reforms either promote or discourage health worker performance. This paper seeks to trace these mechanisms and examines the contextual framework of reform objectives in Uganda and Bangladesh, and health workers' responses to the changes in their working environments by taking a 'realistic evaluation' approach.

Methods

The study findings were generated by triangulating both qualitative and quantitative methods of data collection and analysis among policy technocrats, health managers and groups of health providers. Quantitative surveys were conducted with over 700 individual health workers in both Bangladesh and Uganda and supplemented with qualitative data obtained from focus group discussions and key interviews with professional cadres, health managers and key institutions involved in the design, implementation and evaluation of the reforms of interest.

Results

The reforms in both countries affected the workforce through various mechanisms. In Bangladesh, the effects of the unification efforts resulted in a power struggle and general mistrust between the two former workforce tracts, family planning and health. However positive effects of the reforms were felt regarding the changes in payment schemes. Ugandan findings show how the workforce responded to a strong and rapidly implemented system of decentralisation where the power of new local authorities was influenced by resource constraints and nepotism in recruitment. On the other hand, closer ties to local authorities provided the opportunity to gain insight into the operational constraints originating from higher levels that health staff were dealing with.

Conclusion

Findings from the study suggest that a) reform planners should use the proposed dynamic responses model to help design reform objectives that encourage positive responses among health workers b) the role of context has been underestimated and it is necessary to address broader systemic problems before initiating reform processes, c) reform programs need to incorporate active implementation research systems to learn the contextual dynamics and responses as well as have inbuilt program capacity for corrective measures d) health workers are key stakeholders in any reform process and should participate at all stages and e) some effects of reforms on the health workforce operate indirectly through levels of satisfaction voiced by communities utilising the services.
Dual-lumen catheters for continuous venovenous hemofiltration: limits for blood delivery via femoral vein access and a potential alternative in an experimental setting in anesthetized pigs
Authors: Unger Juliane K , Pietzner Klaus , Francis Roland C , Birnbaum Juergen , Theisen Marc Michael , Lemke Arne-Joern , Niehues Stefan M
Published: February 2007

Introduction

Small intravascular volume, pathophysiological hemorheology, and/or low cardiac output [CO] are assumed to reduce available blood flow rates via common dual-lumen catheters (except for those with a right atrium catheter tip position) in the critically ill patient. We performed an experimental animal study to verify these assumptions.

Methods

Anesthetized, ventilated pigs (35 to 50 kg) were allocated to different hemorheological conditions based on the application of different volume substitutes (that is, colloids and crystalloids, n = 6 to 7 per volume substitute). In a second step, allocation to the final study group was performed after the determination of the highest values for access flow (Qa) via an axial dual-lumen catheter (11 French, 20 cm long, side holes) placed in the femoral vein. High Qa rates (>300 ml/minute) were allocated to the dual-lumen catheter group; low Qa rates were switched to a 'dual-vein approach' using an alternative catheter (8.5-French sheath) for separate blood delivery. Hemodynamics (CO and central venous pressure [CVP]) and blood composition (blood cell counts, plasma proteins, and colloid osmotic pressure) were measured. Catheter tip positions and vessel diameters were exemplified by computed tomography.

Results

Forty-four percent of the animals required an alternative vascular access due to only minimal Qa via the dual-lumen catheter. Neither hemorheologically relevant aspects nor CO and CVP correlated with the Qa achievable via the femoral vein access. Even though the catheter tip of the alternative catheter provided common iliac vein but not caval vein access, this catheter type enabled higher Qa than the dual-lumen catheter positioned in the caval vein.

Conclusion

With respect to the femoral vein approach, none of the commonly assumed reasons for limited Qa via the arterial line of an axial dual-lumen catheter could be confirmed. The 8.5-French sheath, though not engineered for that purpose, performed quite well as an alternative catheter. Thus, in patients lacking right jugular vein access with tip positioning of large-French dual-lumen catheters in the right atrium, it would be of interest to obtain clinical data re-evaluating the 'dual-vein approach' with separate blood delivery via a tip-hole catheter in order to provide high-volume hemofiltration.
Inducibility of the endogenous antibiotic peptide β-defensin 2 is impaired in patients with severe sepsis
Authors: Book Malte , Chen QiXing , Lehmann Lutz E , Klaschik Sven , Weber Stefan , Schewe Jens-Christian , Luepertz Markus , Hoeft Andreas , Stuber Frank
Published: February 2007

Introduction

The potent endogenous antimicrobial peptide human β-defensin 2 (hBD2) is a crucial mediator of innate immunity. In addition to direct antimicrobial properties, different effects on immune cells have been described. In contrast to the well-documented epithelial β-defensin actions in local infections, little is known about the leukocyte-released hBD2 in systemic infectious disorders. This study investigated the basic expression levels and the ex vivo inducibility of hBD2 mRNA in peripheral whole blood cells from patients with severe sepsis in comparison to non-septic critically ill patients and healthy individuals.

Methods

This investigation was a prospective case-control study performed at a surgical intensive care unit at a university hospital. A total of 34 individuals were tested: 16 patients with severe sepsis, 9 critically ill but non-septic patients, and 9 healthy individuals. Serial blood samples were drawn from septic patients, and singular samples were obtained from critically ill non-septic patients and healthy controls. hBD2 mRNA levels in peripheral white blood cells were quantified by real-time polymerase chain reaction in native peripheral blood cells and following ex vivo endotoxin stimulation. Defensin plasma levels were quantified by enzyme-linked immunosorbent assay.

Results

Endotoxin-inducible hBD2 mRNA expression was significantly decreased in patients with severe sepsis compared to healthy controls and non-septic critically ill patients (0.02 versus 0.95 versus 0.52, p < 0.05, arbitrary units). hBD2 plasma levels in septic patients were significantly higher compared to healthy controls and critically ill non-septic patients (541 versus 339 versus 295 pg/ml, p < 0.05).

Conclusion

In contrast to healthy individuals and critically ill non-septic patients, ex vivo inducibility of hBD2 in peripheral blood cells from septic patients is reduced. Impaired hBD2 inducibility may contribute to the complex immunological dysfunction in patients with severe sepsis.