bluuebunny/crossref_metadata_2025 huggingface dataset:
Subcellular Redistribution of the Mitochondrial PG2 Epitope during Development from Cleavage to Primordial Germ Cell Formation in the Rabbit Embryo
Authors: Weckelmann A. , Viebahn C. , Püschel B.
Published: April 2008

Mitochondria are central players in diverse cellular functions and their efficient functioning has dramatic impact on embryonic development. Apparently, proliferation and transmission of well functioning mitochondria to the next generation require ingeniously adapted mechanisms, one of which, the ‘mitochondrial bottleneck’, is thought to occur early in mammalian development during primordial germ cell (PGC) specification. We used an antibody directed against the mitochondrial PG2 epitope, a reliable marker of primordial and adult female germ cells to monitor mitochondrial differentiation in the early rabbit embryo. Early development shows the PG2 epitope either tightly mitochondria-associated (zygote) or diffusely distributed throughout cytoplasm (cleavage stages). Mitochondrial colocalization of the PG2 epitope is regained in the early blastocyst but expression is then retained by the hypoblast and epiblast only, with the epiblast, although the forerunner of PGCs, showing weak and diffuse labeling only. At gastrulation, hypoblast cells lose PG2 expression but intensive PG2 labeling is found again on all mitochondria in the first PGCs and reveals the number of mitochondria to be in the range of 50 to 100 per PGC at this stage. The results highlight the dynamics of PG2 expression during early development and the usefulness of the epitope for testing the bottleneck theory.
Altered Erythrocyte Membrane Protein Composition in Chronic Kidney Disease Stage 5 Patients under Haemodialysis and Recombinant Human Erythropoietin Therapy
Authors: Costa Elísio , Rocha Susana , Rocha-Pereira Petronila , Castro Elisabeth , Miranda Vasco , do Sameiro Faria Maria , Loureiro Alfredo , Quintanilha Alexandre , Belo Luís , Santos-Silva Alice
Published: April 2008

Our aim was to evaluate red blood cell (RBC) membrane protein composition in chronic kidney disease (CKD) stage 5 patients under haemodialysis (HD) and recombinant human erythropoietin (rhEPO) therapy, and its linkage to rhEPO hyporesponsiveness. We evaluated in 63 CKD stage 5 patients (32 responders and 31 non-responders to rhEPO therapy) and in 26 healthy controls RBC count, haematocrit, haemoglobin concentration, haematimetric indices, reticulocyte count, reticulocyte production index, RBC osmotic fragility test and membrane protein analyses. CKD stage 5 patients presented significant changes in membrane protein composition, namely a reduction in spectrin, associated to altered protein 4.1/spectrin and spectrin/band 3 ratios. Non-responder CKD stage 5 patients were more anaemic, with more microcytic and anisocytic RBCs, than responders; significantly altered ankyrin/band 3 and spectrin/ankyrin ratios were also observed. CKD stage 5 patients under HD are associated with an altered protein membrane structure, which seems to the disease itself and/or to the interaction with HD membranes.
Effect of Vagal Nerve Stimulation on Systemic Inflammation and Cardiac Autonomic Function in Patients with Refractory Epilepsy
Authors: Barone Lucy , Colicchio Gabriella , Policicchio Domenico , Di Clemente Francesca , Di Monaco Antonio , Meglio Mario , Lanza Gaetano A. , Crea Filippo
Published: April 2008

Objective: Recent data suggest that vagus nerve stimulation (VNS) can inhibit cytokine release by inflammatory cells. Accordingly, an association between impaired cardiac parasympathetic function, as assessed by heart rate variability (HRV), and increased markers of inflammation has recently been reported. In this study we assessed the effect of direct left VNS on inflammatory markers and HRV in patients with refractory epilepsy. Methods: A 24-hour electrocardiogram Holter recording was performed both at baseline and after 3 months of left VNS in 8 patients (age 32 ± 24 years, 2 men) who underwent implantation of a VNS device because of refractory epilepsy. Tumor necrosis factor-α, interleukin-6 and C-reactive protein serum levels were measured, as markers of inflammation, at the same times. Results: No significant changes were found after 3 months of left VNS, compared to baseline, both for HRV variables and inflammatory markers. Also, no consistent correlation could be demonstrated between HRV parameters and inflammatory markers in these patients. Conclusions: Our data in epileptic patients without cardiovascular disease failed to show a significant effect of left VNS on cardiac autonomic function and on systemic inflammation at short-term follow-up.
Prokineticin Receptor-1 Induces Neovascularization and Epicardial-Derived Progenitor Cell Differentiation
Authors: Urayama Kyoji , Guilini Célia , Turkeri Gulen , Takir Selcuk , Kurose Hitoshi , Messaddeq Nadia , Dierich Andrée , Nebigil Canan G.
Published: April 2008

Objective—

Identification of novel factors that contribute to myocardial repair and collateral vessel growth hold promise for treatment of heart diseases. We have shown that transient prokineticin receptor-1 (PKR1) gene transfer protects the heart against myocardial infarction in a mouse model. Here, we investigated the role of excessive PKR1 signaling in heart.

Methods and Results—

Transgenic mice overexpressing PKR1 in cardiomyocytes displayed no spontaneous abnormalities in cardiomyocytes but showed an increased number of epicardial-derived progenitor cells (EPDCs), capillary density, and coronary arterioles. Coculturing EPDCs with H9c2 cardiomyoblasts overexpressing PKR1 promotes EPDC differentiation into endothelial and smooth muscle cells, mimicking our transgenic model. Overexpressing PKR1 in H9c2 cardiomyoblasts or in transgenic hearts upregulated prokineticin-2 levels. Exogenous prokineticin-2 induces significant outgrowth from neonatal and adult epicardial explants, promoting EPDC differentiation. These prokineticin-2 effects were abolished in cardiac explants from mice with PKR1-null mutation. Reduced capillary density and prokineticin-2 levels in PKR1-null mutant hearts supports the hypothesis of an autocrine/paracrine loop between PKR1 and prokineticin-2.

Conclusion—

Cardiomyocyte-PKR1 signaling upregulates its own ligand prokineticin-2 that acts as a paracrine factor, triggering EPDCs proliferation/differentiation. This study provides a novel insight for possible therapeutic strategies aiming at restoring pluripotency of adult EPDCs to promote neovasculogenesis by induction of cardiomyocyte PKR1 signaling.
When Arguments Prevail Over Power: The CITES Procedure for the Listing of Endangered Species
Authors: Gehring Thomas , Ruffing Eva
Published: April 2008

The legitimacy and effectiveness of the Convention on International Trade in Endangered Species of Wild Flora and Fauna (CITES) depends on problem-adequate listing decisions. Decisions are frequently highly controversial, because they commit the member states to imposing trade restrictions on listed species. We examine whether—and how—CITES' impressive institutional apparatus deprives the member states of their bargaining power and empowers actors who can make reasoned arguments on the merits of a listing decision. For this purpose, we demonstrate theoretically that appropriately designed decision-making procedures can diminish stake-holders' opportunities for exploiting their bargaining power and provide room for reason-based deliberation. Subsequently, we explore member states' and other stakeholders' incentives, created by the CITES listing procedure, for refraining from bargaining and accepting scientifically sound decisions. Finally, we examine three recent controversial listing decisions as examples of the actual operation of the listing procedure.
Making Transparency Work
Authors: Florini Ann
Published: April 2008

A commentary on Gupta and Mason.
Cool Rationalities and Hot Air: A Rhetorical Approach to Understanding Debates on Renewable Energy
Authors: Barry John , Ellis Geraint , Robinson Clive
Published: April 2008

A key obstacle to the wide-scale development of renewable energy is that public acceptability of wind energy cannot be taken for granted when wind energy moves from abstract support to local implementation. Drawing on a case study of opposition to the siting of a proposed off-shore wind farm in Northern Ireland, we offer a rhetorical analysis of a series of representative documents drawn from government, media, pro- and anti-wind energy sources, which identifies and interprets a number of discourses of objection and support. The analysis indicates that the key issue in terms of the transition to a renewable energy economy has little to do with the technology itself. Understanding the different nuances of pro- and anti-wind energy discourses highlights the importance of thinking about new ways of looking at these conflicts. These include adopting a “conflict resolution” approach and “upstreaming” public involvement in the decision-making process and also the counter-productive strategy of assuming that objection is based on ignorance (which can be solved by information) or NIMBY thinking (which can be solved by moral arguments about overcoming “free riders”).
Stigmatization and Discrimination of HIV/AIDS Women in Kenya: A Violation of Human Rights and its Theological Implications
Authors: Mwaura Philomena Njeri
Published: April 2008

Despite spirited efforts by the African governments, the church, faith based organizations, non-governmental organizations, individuals and communities, available statistics confirm that the AIDs epidemic continues to advance. This has been exacerbated by grinding poverty, patriarchal gender power relations that render women powerless, damaging practices supported by both traditional and modern cultures, ineffective health care systems, stigma and discrimination. Women and girl children suffer in greater proportions relative to men. Their human rights have been violated inside and outside the church. There is therefore a need to prioritize women's human rights in order for nation states and individuals to implement successful public health strategies, behaviour change and the restoration and maintenance of human dignity. The church should consistently condemn the sin of stigmatization and discrimination. It should revise its education in this area and develop an ecclesiology that would effectively respond to the HIV/Aids epidemic in a just, loving and gender inclusive manner.
Variability of the Great Plains Low-Level Jet: Large-Scale Circulation Context and Hydroclimate Impacts
Authors: Weaver Scott J. , Nigam Sumant
Published: April 2008

Variability of the Great Plains low-level jet (GPLLJ) is analyzed from the perspective of larger-scale, lower-frequency influences and regional hydroclimate impacts as opposed to the usual analysis of its frequency, diurnal variability, and mesoscale structure. The circulation-centric core analysis is conducted with monthly data from the high spatiotemporal resolution, precipitation-assimilating North American Regional Reanalysis, and the 40-yr ECMWF Re-Analysis (ERA-40) (as necessary) to identify the recurrent patterns of GPLLJ variability and their large-scale circulation links. The links are first investigated from regressions of an index representing meridional wind speed in the climatological jet-core region; the core region itself is defined from analysis of seasonal and diurnal variability of the jet structure and moisture fluxes.

The analysis reveals that GPLLJ variability is, indeed, linked to coherent, large-scale, upper-level height patterns over the Pacific and North Atlantic Oscillation (NAO) variability in the Atlantic. A Rossby wave source analysis shows the Pacific height pattern to be potentially linked to tropical diabatic heating anomalies in the west-central basin and in the eastern Pacific sector. EOF analysis of GPLLJ variability shows it to be composed of three modes that, together, account for ∼75% of the variance. The modes represent the strengthening/expansion of the jet core (38%), with a strong precipitation impact on the northern Great Plains, and linked to post-peak-phase ENSO variability; meridional shift of the GPLLJ (23%), with a Gulf states precipitation focus, and linked to pre-peak-phase ENSO variability; and in-place strengthening of the GPLLJ (12%), with dipolar influence on Great Plains and Gulf states precipitation, and linked to summer NAO variability.
A Simple Equation for Regional Climate Change and Associated Uncertainty
Authors: Giorgi Filippo
Published: April 2008

Simple equations are developed to express regional climate changes for the twenty-first century and associated uncertainty in terms of the global temperature change (GTC) without a dependence on the underlying emission pathways. The equations are applied to regional temperature and precipitation changes over different regions of the world, and relevant parameters are calculated using the latest multimodel ensemble of global climate change simulations. Examples are also shown of how to use the equations to develop probability density functions (PDFs) of regional climate change based on PDFs of GTC. The main advantage of these equations is that they can be used to estimate regional changes from GTC obtained either from simple and intermediate complexity models or from target CO2 stabilization concentrations.
Increasing Geothermal Energy Demand: The Need for Urbanization of the Drilling Industry
Authors: Teodoriu Catalin , Falcone Gioia
Published: April 2008

Drilling wells in urban spaces requires special types of rigs that do not conflict with the surrounding environment. For this, a mutation of the current drilling equipment is necessary into what can be defined as an “urbanized drilling rig.” Noise reduction, small footprint, and “good looking” rigs all help persuade the general public to accept the presence of drilling rigs in their neighborhood. This article reviews international projects that aim to integrate drilling with the urban infrastructures with a special focus on geothermal projects. Case studies are presented where tailored drilling rigs and new technology have already been implemented. The review aids the analysis of the main urban-related technical aspects of modern drilling rigs. Finally, the new trends in integrating architecture, urbanism, and drilling rig design are discussed.
Understanding the Economic Consequences of Mexican Immigration to the United States
Authors: Donato Katharine M.
Published: April 2008

Recent decades have witnessed dramatic increases in U.S. immigration, especially from Mexico. In a new book, Mexican Immigration to the United States, George Borjas continues a long line of research that articulates how this rising tide of immigration is linked to our national well-being. This edited book brings together a diverse set of articles written by some of the nation's best economists and presented in 2005 at a conference in Cambridge, Massachusetts. No doubt, it is an important book to read if one is interested in understanding the supply side concerns of economists interested in immigration. Yet despite my own keen interest in this topic, the book as a whole only narrowly addresses the economic effects of Mexican immigration because it fails to incorporate sociological and other perspectives. Such a missed opportunity suggests how much more needs to be done to understand the economic outcomes of immigrants in U.S. labor markets.
Long-Term Sickness Absence Due to Burnout: Absentees' Experiences
Authors: Eriksson Ulla-Britt , Starrin Bengt , Janson Staffan
Published: April 2008

In the late 1990s, there was a marked increase in Sweden in long-term sickness absence with mental diagnoses. In the extensive research on burnout, little attention has been paid to the link with sickness absence. Our aim in this study was to discover what caused burnout, or such severe stress that it led to long-term sickness absence (> 28 days). We interviewed 32 individuals on long-term sickness absence with a diagnosis of burnout and used grounded theory to analyze the data. We believe that events prior to the sickness absence can be understood as a process of emotional deprivation, and we described the process in terms of a flight of stairs with eight steps: “The Burnout Stairs.” We argue that the emotion conveying the process of emotional deprivation is unacknowledged shame, which has its basis in poor social relations at work. We discuss the study's limitations and the need for further research in this field.
Making Collaboration Work in Inclusive High School Classrooms
Authors: Hines Joy T.
Published: April 2008

The growing number of children with disabilities who are served in general education classrooms has made it necessary for general and special education teachers to work together to ensure that all students receive an appropriate education. As the instructional leader, the school principal is presented with the challenge of facilitating and guiding effective collaborative relationships among teachers. This article presents a brief discussion of collaboration in inclusive high school classrooms and describes how administrators can facilitate the effective use of collaboration skills.
The Affective Impact of Exercise Intensity That Slightly Exceeds the Preferred Level
Authors: Lind Erik , Ekkekakis Panteleimon , Vazou Spiridoula
Published: April 2008

We examined the affective consequences of an exercise intensity that slightly exceeded the preferred level. Twenty-five middle-age sedentary women participated in two 20-min treadmill exercise bouts, one during which they could select the speed and one during which the speed was 10 per cent higher than the self-selected. During the bout at self-selected intensity, ratings of pleasure remained stable, whereas during the imposed-intensity bout pleasure decreased. Therefore, even a minor increase in exercise intensity beyond the level that a new exerciser would have self-selected can bring about a decrease in pleasure. Over time, such experiences could lower adherence.
Psychological and Behavioural Impact of Genetic Testing Smokers for Lung Cancer Risk
Authors: Sanderson Saskia C. , Humphries Steve E. , Hubbart Christina , Hughes Eluned , Jarvis Martin J. , Wardle Jane
Published: April 2008

The behavioural and psychological impact of genetic testing for lung cancer susceptibility was examined among smokers ( N = 61) who were randomly allocated to a GSTM1 genetic testing group (with GSTM1-missing or GSTM1-present result) or no-test control group. The GSTM1-missing (higher risk) group reported greater motivation to quit smoking, and both genetic testing groups reported lower depression than the control group at one-week follow-up ( p < .05 for all). Differences were not significant at two months follow-up. This study indicates the feasibility of much-needed research into the risks and benefits for individuals of emerging lifestyle-related genetic susceptibility tests.
The glocalization of journalism ethics
Authors: Wasserman Herman , Rao Shakuntala
Published: April 2008

This article addresses globalization's effects on journalism ethics in South Africa and India. It shows the ways in which the debates and issues of journalism ethics are being resolved through the process which scholars have termed as glocalization. Both in South Africa and India we found a two-way relationship between global and local epistemologies and practices. By using examples from each country, we suggest that journalism ethics is going through a process of resignification in the local arena. We suggest a global-to-local theoretical matrix that takes into consideration the complexity of journalism ethics in specific cultural and national contexts.
Simultaneous inference for multiple testing and clustering via a Dirichlet	process mixture model
Authors: Dahl David B , Mo Qianxing , Vannucci Marina
Published: April 2008

We propose a Bayesian nonparametric regression model that exploits clustering for increased sensitivity in multiple hypothesis testing. We build on the recently proposed BEMMA (Bayesian Effects Models for Microarrays) method which is able to model dependence among objects through clustering and then estimates hypothesis-testing parameters averaged over clustering uncertainty. We propose several improvements. First, we separate the clustering of the regression coefficients from the part of the model that accommodates heteroscedasticity. Second, our model accommodates a wider class of experimental designs, such as permitting covariates and not requiring independent sampling. Third, we provide a more satisfactory treatment of nuisance parameters and some hyperparameters. Finally, we do not require the arbitrary designation of a reference treatment. The proposed method is compared in a simulation study to ANOVA and the BEMMA methods.
On a partially specified Bayesian nonparametric model for earthquakes	occurrences
Authors: Ruggeri Fabrizio
Published: April 2008

We consider the case of a bivariate Dirichlet process model in which the parameter is known only through its marginal distributions. A Fréchet class on the parameter is therefore entertained and, consequently, a class of Dirichlet processes is obtained. We analyze the notion of robustness in such environment and introduce some measures of robustness. The ideas are finally illustrated in an example about earthquakes occurrences.
Markers of Inflammation in Patients With Symptomatic and Asymptomatic Carotid Artery Stenosis: A Case-Control Study
Authors: Debing Erik , Peeters Els , Demanet Christian , De Waele Marc , Van den Brande Pierre
Published: April 2008

Objectives There is evidence that inflammation plays a role in the pathogenesis of atherosclerosis. We compared levels of inflammatory markers between patients undergoing carotid endarterectomy (CEA) and controls, and between patients with symptomatic and asymptomatic internal carotid artery (ICA) stenosis.

Materials and Methods A total of 180 patients with ICA stenosis were compared with 180 age-matched and sex-matched controls. The biomarkers evaluated were high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule 1, soluble vascular cell adhesion molecule 1 (sVCAM-1), and interleukin-6 (IL-6).

Results The levels of hs-CRP, sVCAM-1, and IL-6 in the CEA group were significantly higher than in the control group (1.87 mg/mL vs 1.44 mg/mL, P = .011; 1408 ng/dL vs 672 ng/dL, P < .001; 11.9 pg/mL vs 6.3 pg/mL, P < .001). Multivariate linear regression analysis, adjusted for all clinical and physiologic parameters, showed a significant association between ICA stenosis and hs-CRP, sVCAM-1, and IL-6 concentrations. Analysis of symptomatic (n = 101) and asymptomatic (n = 79) ICA stenosis did not detect a difference in levels of these markers.

Conclusions Our study suggests that inflammatory markers could serve as markers for ICA atherosclerosis but are not useful to identify carotid plaque at risk for symptomatic conversion.
Changes in exercise haemodynamics during treatment in pulmonary arterial hypertension
Authors: Provencher S. , Hervé P. , Sitbon O. , Humbert M. , Simonneau G. , Chemla D.
Published: April 2008

Improvement in exercise capacity may not be associated with significant changes in resting pulmonary haemodynamics. The present prospective study documented the relationships between improvement in 6-min walking distance (6MWD) and changes in resting and exercise pulmonary haemodynamics after treatment in patients with idiopathic pulmonary arterial hypertension (IPAH).

A total of 42 IPAH patients underwent supine submaximal exercise haemodynamic assessments at baseline and after 5±2 months of therapy. The 6MWD, the corresponding chronotropic response (peak minus resting heart rate), and resting and exercise haemodynamic variables were analysed. The isoflow was defined as the lowest of the pre- and post-treatment peak cardiac index (CI). The extrapolated isoflow mean pulmonary artery pressure (P̄pa) was used to characterise changes inP̄pa–CI regression lines following treatment.

Patients were given bosentan (n = 28), epoprostenol (n = 12) or both. The 6MWD increased significantly, from 399±88 to 442±86 m. On univariate analysis, changes in 6MWD correlated with changes in isoflowP̄pa, chronotropic response, resting haemodynamics (CI, pulmonary vascular resistance and mixed venous oxygen saturation) and exercise haemodynamics (peak CI). On multivariate analysis, only changes in isoflowP̄paand chronotropic response were independently associated with changes in 6MWD.

Improvement in exercise tolerance with chronic therapy is independently related to improvement in pulmonary haemodynamics measured in exercise but not in resting conditions.
Impact of acute exposure to tobacco smoke on gelatinases in the bronchoalveolar space
Authors: Glader P. , Eldh B. , Bozinovski S. , Andelid K. , Sjöstrand M. , Malmhäll C. , Anderson G. P. , Riise G. C. , Qvarfordt I. , Lindén A.
Published: April 2008

Clinical studies have indicated increased gelatinase activity in the airways of patients suffering from chronic obstructive pulmonary disease caused by tobacco smoke. The present study aimed to determine whether acute exposure to tobacco smokeper secauses a substantial and lasting impact on gelatinases and their inhibitors in the peripheral airways of atopic and nonatopic human subjects.

Bronchoscopy with bronchoalveolar lavage (BAL) was performed on occasional smokers with and without atopy before and after smoking 10 cigarettes over a 48-h period. Samples from a group of never-smokers not exposed to tobacco smoke served as controls. Gelatinase identity and activity were measured using zymography, and gelatinase activity assay and concentrations of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of MMP (TIMP)-1 and TIMP-2 were measured using ELISA.

The results revealed no pronounced changes in identity, net activity or concentration of the gelatinases or changes in concentrations of TIMP-1 and TIMP-2 in BAL fluid before and after acute exposure to tobacco smoke.

In conclusion, the present experimental study indicates that acute exposure to tobacco smoke does not cause any substantial impact on gelatinases or their inhibitors in the peripheral airways, irrespective of atopy status, a finding that is compatible with the fact that it takes many years of tobacco smoking to establish chronic obstructive pulmonary disease.
Health belief model predicts adherence to CPAP before experience with CPAP
Authors: Olsen S. , Smith S. , Oei T. , Douglas J.
Published: April 2008

Adherence to continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea (OSA) is often poor. Biomedical indices explain little of the variance in CPAP use. The present study tested a health belief model of adherence in order to determine the contribution of psychological constructs as compared to biomedical indices in the prediction of CPAP adherence.

Consecutive patients (n = 77) newly diagnosed with OSA and naïve to CPAP treatment (had never tried CPAP before) completed questionnaires at baseline (prior to CPAP treatment). The questionnaires assessed: outcome expectancy with treatment, self-efficacy, functional outcomes of sleepiness, and perceived risk of negative health outcomes. Physiological data were obtained from a standard clinical diagnostic sleep study. CPAP adherence was assessed at 4-month follow-up.

Health belief model constructs alone explained 21.8% of the variance in CPAP adherence, whereas health belief model constructs and biomedical indices together explained 31.8% of the variance in CPAP adherence. The greatest proportion of CPAP adherence was explained by higher outcome expectancies with treatment, greater functional limitations as a result of sleepiness and lower risk perception.

The results suggest that patients have developed beliefs and expectations about obstructive sleep apnoea and continuous positive airway pressure even before they try continuous positive airway pressure treatment. These beliefs and expectations predict the patients' adherence to effective therapy.
Reference values for peak flow and FEV1variation in healthy schoolchildren using home spirometry
Authors: Brouwer A. F. J. , Roorda R. J. , Duiverman E. J. , Brand P. L. P.
Published: April 2008

Current reference values for diurnal peak flow variation in healthy children (median 8.2%; 95th percentile 31%) are so high that considerable overlap exists with those of asthmatic children. These values have been obtained using written peak flow diaries, which are unreliable. The aim of the present study was to obtain reliable reference values for the variation in peak flow and forced expiratory volume in one second (FEV1) in healthy schoolchildren using home spirometry with electronic data storage.

Healthy schoolchildren (n = 204; 100 males) aged 6–16 yrs measured their peak flow and FEV1twice daily for 2 weeks using an electronic home spirometer. The variation in peak flow and FEV1were calculated as a diurnal amplitude as a percentage of the day’s mean.

The mean peak flow variation was 6.2% (95th percentile 12.3%) and the mean FEV1variation was 5.7% (95th percentile 11.8%).

Using home spirometry with electronic data storage, healthy schoolchildren show considerably less peak flow and forced expiratory volume in one second variation than previously reported on the basis of written peak flow diaries. Being the 95th percentiles of the distributions in healthy children, a peak flow variation of 12.3% and an forced expiratory volume in one second variation of 11.8% are suggested as cut-off values for disease when using home spirometry.
Search for the genes involved in oocyte maturation and early embryo development in the hen
Authors: Elis Sebastien , Batellier Florence , Couty Isabelle , Balzergue Sandrine , Martin-Magniette Marie-Laure , Monget Philippe , Blesbois Elisabeth , Govoroun Marina S
Published: April 2008

Background

The initial stages of development depend on mRNA and proteins accumulated in the oocyte, and during these stages, certain genes are essential for fertilization, first cleavage and embryonic genome activation. The aim of this study was first to search for avian oocyte-specific genes using an in silico and a microarray approaches, then to investigate the temporal and spatial dynamics of the expression of some of these genes during follicular maturation and early embryogenesis.

Results

The in silico approach allowed us to identify 18 chicken homologs of mouse potential oocyte genes found by digital differential display. Using the chicken Affymetrix microarray, we identified 461 genes overexpressed in granulosa cells (GCs) and 250 genes overexpressed in the germinal disc (GD) of the hen oocyte. Six genes were identified using both in silico and microarray approaches. Based on GO annotations, GC and GD genes were differentially involved in biological processes, reflecting different physiological destinations of these two cell layers. Finally we studied the spatial and temporal dynamics of the expression of 21 chicken genes. According to their expression patterns all these genes are involved in different stages of final follicular maturation and/or early embryogenesis in the chicken. Among them, 8 genes (btg4, chkmos, wee, zpA, dazL, cvh, zar1 and ktfn) were preferentially expressed in the maturing occyte and cvh, zar1 and ktfn were also highly expressed in the early embryo.

Conclusion

We showed that in silico and Affymetrix microarray approaches were relevant and complementary in order to find new avian genes potentially involved in oocyte maturation and/or early embryo development, and allowed the discovery of new potential chicken mature oocyte and chicken granulosa cell markers for future studies. Moreover, detailed study of the expression of some of these genes revealed promising candidates for maternal effect genes in the chicken. Finally, the finding concerning the different state of rRNA compared to that of mRNA during the postovulatory period shed light on some mechanisms through which oocyte to embryo transition occurs in the hen.
Long-term outcome of infective endocarditis: A study on patients surviving over one year after the initial episode treated in a Finnish teaching hospital during 25 years
Authors: Heiro Maija , Helenius Hans , Hurme Saija , Savunen Timo , Metsärinne Kaj , Engblom Erik , Nikoskelainen Jukka , Kotilainen Pirkko
Published: April 2008

Background

Only a few previous studies have focused on the long-term prognosis of the patients with infective endocarditis (IE). Our purpose was to delineate factors potentially associated with the long-term outcome of IE, recurrences of IE and requirement for late valve surgery.

Methods

A total of 326 episodes of IE in 303 patients were treated during 1980–2004 in the Turku University Hospital. We evaluated the long-term outcome and requirement for late valve surgery for 243 of these episodes in 226 patients who survived longer than 1 year after the initial admission. Factors associated with recurrences were analysed both for the 1-year survivors and for all 303 patients.

Results

The mean (SD) follow-up time for the 1-year survivors was 11.5 (7.3) years (range 25 days to 25.5 years). The overall survival was 95%, 82%, 66%, 51% and 45% at 2, 5, 10, 15 and 20 years. In age and sex adjusted multivariate analyses, significant predictors for long-term overall mortality were heart failure within 3 months of admission (HR 1.97, 95% CI 1.27 to 3.06; p = 0.003) and collagen disease (HR 2.54, 95% CI 1.25 to 5.19; p = 0.010) or alcohol abuse (HR 2.39, 95% CI 1.30 to 4.40; p = 0.005) as underlying conditions, while early surgery was significantly associated with lower overall mortality rates (HR 0.31, 95% CI 0.17 to 0.58; p < 0.001). Heart failure was also significantly associated with the long-term cardiac mortality (p = 0.032). Of all 303 patients, 20 had more than 1 disease episode. Chronic dialysis (p = 0.002), intravenous drug use (p = 0.002) and diabetes (p = 0.015) were significant risk factors for recurrent episodes of IE, but when analysed separately for the 1-year survivors, only chronic dialysis remained significant (p = 0.017). Recurrences and late valve surgery did not confer a poor prognosis.

Conclusion

Heart failure during the index episode of IE was the complication, which significantly predicted a poor long-term outcome. Patients who underwent surgery during the initial hospitalisation for IE faired significantly better than those who did not.
Efficacy of amodiaquine in the treatment of uncomplicated falciparum malaria in young children of rural north-western Burkina Faso
Authors: Mandi Germain , Mockenhaupt Frank P , Coulibaly Boubacar , Meissner Peter , Müller Olaf
Published: April 2008

Background

Combination therapy has become a new paradigm in malaria treatment. Amodiaquine is a common partner drug in different malaria combination therapies used or investigated in sub-Saharan Africa, but data on its efficacy as a single drug are scarce.

Methods

The objective of the study was to determine the efficacy of amodiaquine against falciparum malaria in neighbouring rural and urban areas of north-western Burkina Faso. The study was designed as an uncontrolled trial in children aged 6–59 months with uncomplicated falciparum malaria in the Nouna Health District.

Results

During the rainy season 2005, 117 children were enrolled, 62 from the rural and 55 from the urban study area. The crude adequate clinical and parasitological response (ACPR) rate was 103/117 (88%) by day 14 but decreased to 28/117 (24%) by day 28. After PCR correction for reinfections, ACPR rates were 108/117 (92%) and 71/117 (61%) by day 14 and day 28, respectively. There were no significant differences in efficacy between urban and rural areas. The Plasmodium falciparum crt K76T mutation not predict AQ failure, but was selected in parasites re-appearing following treatment. No serious adverse events occurred and only 16 other adverse events were recorded.

Conclusion

Compared to chloroquine, amodiaquine is more effective against uncomplicated falciparum malaria in Burkina Faso. However, a considerable degree of amodiaquine resistance already exists and it is currently unclear how this resistance will develop when amodiaquine in combination with other drugs is used on a large scale.

Trial registration

Current Controlled Trials ISRCTN73824458.
The underlying mechanisms for development of hypertension in the metabolic syndrome
Authors: Yanai Hidekatsu , Tomono Yoshiharu , Ito Kumie , Furutani Nobuyuki , Yoshida Hiroshi , Tada Norio
Published: April 2008

High blood pressure is an important constituent of the metabolic syndrome. However, the underlying mechanisms for development of hypertension in the metabolic syndrome are very complicated and remain still obscure. Visceral/central obesity, insulin resistance, sympathetic overactivity, oxidative stress, endothelial dysfunction, activated renin-angiotensin system, increased inflammatory mediators, and obstructive sleep apnea have been suggested to be possible factors to develop hypertension in the metabolic syndrome. Here, we will discuss how these factors influence on development of hypertension in the metabolic syndrome.
Iraq War mortality estimates: A systematic review
Authors: Tapp Christine , Burkle Frederick M , Wilson Kumanan , Takaro Tim , Guyatt Gordon H , Amad Hani , Mills Edward J
Published: April 2008

Background

In March 2003, the United States invaded Iraq. The subsequent number, rates, and causes of mortality in Iraq resulting from the war remain unclear, despite intense international attention. Understanding mortality estimates from modern warfare, where the majority of casualties are civilian, is of critical importance for public health and protection afforded under international humanitarian law. We aimed to review the studies, reports and counts on Iraqi deaths since the start of the war and assessed their methodological quality and results.

Methods

We performed a systematic search of 15 electronic databases from inception to January 2008. In addition, we conducted a non-structured search of 3 other databases, reviewed study reference lists and contacted subject matter experts. We included studies that provided estimates of Iraqi deaths based on primary research over a reported period of time since the invasion. We excluded studies that summarized mortality estimates and combined non-fatal injuries and also studies of specific sub-populations, e.g. under-5 mortality. We calculated crude and cause-specific mortality rates attributable to violence and average deaths per day for each study, where not already provided.

Results

Thirteen studies met the eligibility criteria. The studies used a wide range of methodologies, varying from sentinel-data collection to population-based surveys. Studies assessed as the highest quality, those using population-based methods, yielded the highest estimates. Average deaths per day ranged from 48 to 759. The cause-specific mortality rates attributable to violence ranged from 0.64 to 10.25 per 1,000 per year.

Conclusion

Our review indicates that, despite varying estimates, the mortality burden of the war and its sequelae on Iraq is large. The use of established epidemiological methods is rare. This review illustrates the pressing need to promote sound epidemiologic approaches to determining mortality estimates and to establish guidelines for policy-makers, the media and the public on how to interpret these estimates.
Multi-Institutional Phase I Trials of Anticancer Agents
Authors: Dowlati Afshin , Manda Sudhir , Gibbons Joseph , Remick Scot C. , Patrick Lauren , Fu Pingfu
Published: April 2008

Purpose

Physicians involved in the conduct of phase I studies of novel anticancer agents have raised concerns about the emergence of multi-institutional phase I trials and about using the optimal biologic dose (OBD) as an alternative to the maximum-tolerated dose (MTD) as the primary end point in early drug development. We sought to determine the factors associated with multi-institutional phase I studies and OBD determination.

Patients and Methods

We reviewed all published phase I trials between January 1998 and June 2006 from two major clinical cancer journals. The following components from each trial were determined: number of participating sites, sponsor, nation where study was conducted, MTD or OBD established, number of patients accrued, mechanism of action of the studied agent, accrual time, and tumor type.

Results

We identified 463 trials. Fifty-six percent were performed in single institutions. Only 30% reported accrual time. The number of patients enrolled on single institution studies was significantly lower than on multi-institutional studies (P < .05), but there was no difference in accrual time. There was no association between the number of institutions and the sponsor or the mechanism of drug action. National Institutes of Health–sponsored trials enrolled fewer patients per trial than pharmaceutical-sponsored trials (P < .05). Although 99% of trials with cytotoxic agents determined an MTD, only 64% of trials with targeted agents did.

Conclusion

Multi-institutional phase I studies do not decrease the time to study completion and result in an increase in number of patients per trial. One third of trials with targeted agents failed to determine an MTD.
SoxB1 transcription factors and Notch signaling use distinct mechanisms to regulate proneural gene function and neural progenitor differentiation
Authors: Holmberg Johan , Hansson Emil , Malewicz Michal , Sandberg Magnus , Perlmann Thomas , Lendahl Urban , Muhr Jonas
Published: April 2008

The preservation of a pool of neural precursors is a prerequisite for proper establishment and maintenance of a functional central nervous system(CNS). Both Notch signaling and SoxB1 transcription factors have been ascribed key roles during this process, but whether these factors use common or distinct mechanisms to control progenitor maintenance is unsettled. Here, we report that the capacity of Notch to maintain neural cells in an undifferentiated state requires the activity of SoxB1 proteins, whereas the mechanism by which SoxB1 block neurogenesis is independent of Notch signaling. A common feature of Notch signaling and SoxB1 proteins is their ability to inhibit the activity of proneural bHLH proteins. Notch represses the transcription of proneural bHLH genes, while SoxB1 proteins block their neurogenic capacity. Moreover, E-proteins act as functional partners of proneural proteins and the suppression of E-protein expression is an important mechanism by which Notch counteracts neurogenesis. Interestingly, in contrast to the Hes-dependent repression of proneural genes, suppression of E-protein occurs in a Hes-independent fashion. Together, these data reveal that Notch signaling and SoxB1 transcription factors use distinct regulatory mechanisms to control proneural protein function and to preserve neural cells as undifferentiated precursors.
Zic2 promotes axonal divergence at the optic chiasm midline by EphB1-dependent and -independent mechanisms
Authors: García-Frigola Cristina , Carreres Maria Isabel , Vegar Celia , Mason Carol , Herrera Eloísa
Published: April 2008

Axons of retinal ganglion cells (RGCs) make a divergent choice at the optic chiasm to cross or avoid the midline in order to project to ipsilateral and contralateral targets, thereby establishing the binocular visual pathway. The zinc-finger transcription factor Zic2 and a member of the Eph family of receptor tyrosine kinases, EphB1, are both essential for proper development of the ipsilateral projection at the mammalian optic chiasm midline. Here, we demonstrate in mouse by functional experiments in vivo that Zic2 is not only required but is also sufficient to change the trajectory of RGC axons from crossed to uncrossed. In addition, our results reveal that this transcription factor regulates the expression of EphB1 in RGCs and also suggest the existence of an additional EphB1-independent pathway controlled by Zic2 that contributes to retinal axon divergence at the midline.
Changing abilities in recognition of unfamiliar face photographs through childhood and adolescence: Performance on a test of non‐verbal immediate memory (Warrington RMF) from 6 to 16 years
Authors: Lawrence K. , Bernstein D. , Pearson R. , Mandy W. , Campbell R. , Skuse D.
Published: April 2008

A commonly used test of non‐verbal memory, which measures recognition for unfamiliar face pictures, was developed byWarrington (1984), the Recognition Memory for Faces (RMF) test. The task has been widely used in adults in relation to neurological impairment of face recognition. We examined the relationship of RMF scores to age in 500 young people aged between 6 and 16 years. A linear relationship obtained between 6 and 10 years, followed by a ‘plateau’ between the ages of 10 and 13, followed by further improvement. Abilities on the test correlated with both verbal and non‐verbal intelligence, but the nonlinear function relating age and RMF survived partialling for intelligence in the younger age groups. The improvement of the adolescents compared with older children also survived partialling for IQ. We found no significant influence of gender or reported pubertal status (which was not obtained for all participants) on RMF once age was taken into account. Performance on other face‐processing tasks (emotion classification and accuracy in line of sight detection) correlated significantly, if moderately, with RMF scores. Despite its age and imperfections, RMF test may nevertheless be a useful indicator of ‘face expertise’ in a developmental context.
Reduced fixation on the upper area of personally familiar faces following acquired prosopagnosia
Authors: de Xivry Jean‐Jacques Orban , Ramon Meike , Lefèvre Philippe , Rossion Bruno
Published: April 2008

Selective impairment of face recognition following brain damage, as in acquired prosopagnosia, may cause a dramatic loss of diagnosticity of the eye area of the face and an increased reliance on the mouth for identification (Caldara et al., 2005). To clarify the nature of this phenomenon, we measured eye fixation patterns in a case of pure prosopagnosia (PS, Rossion et al., 2003) during her identification of photographs of personally familiar faces (27 children of her kindergarten). Her age‐matched colleague served as a control. Consistent with previous evidence, the normal control identified the faces within two fixations located just below the eyes (central upper nose). This pattern (location and duration) of fixations remained unchanged even by increasing difficulty by presenting anti‐caricatures of the faces. In contrast, the great majority of the patient's fixations, irrespective of her accuracy, were located on the mouth. Overall, these observations confirm the abnormally reduced processing of the upper area of the face in acquired prosopagnosia. Most importantly, the prosopagnosic patient also fixated the area of the eyes spontaneously in between the first and last fixation, ruling out alternative accounts of her behaviour such as, for example, avoidance or failure to orient attention to the eyes, as observed in autistic or bilateral amygdala patients. Rather, they reinforce our proposal of a high‐level perceptual account (Caldara et al., 2005), according to which acquired prosopagnosic patients have lost the ability to represent multiple elements of an individual face as a perceptual unit (holistic face perception). To identify a given face, they focus very precisely on local features rather than seeing the whole of a face from its diagnostic centre (i.e. just below the eyes). The upper area of the face is particularly less attended to and less relevant for the prosopagnosic patient because it contains multiple features that require normal holistic perception in order to be the most diagnostic region. Consequently, prosopagnosic patients develop a more robust representation of the mouth, a relatively isolated feature in the face that may contain more information than any single element of the upper face area, and is thus sampled repeatedly for resolving ambiguity in the process of identification.