bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized double‐blind, placebo‐controlled trial of sublingual immunotherapy with a Pru p 3 quantified peach extract
Authors: Fernández‐Rivas M. , Garrido Fernández S. , Nadal J. A. , Alonso Díaz de Durana M. D. , García B. E. , González‐Mancebo E. , Martín S. , Barber D. , Rico P. , Tabar A. I. 
Published: January 2009

Background:  Peach allergy is highly prevalent in the Mediterranean area; it is persistent and potentially severe, and therefore a prime target for immunotherapy. We aimed to study the efficacy and safety of sublingual immunotherapy (SLIT) with a peach extract quantified in mass units for Pru p 3, the peach lipid transfer protein.Methods:  Randomized, double‐blind, placebo‐controlled (DBPC) clinical trial. The main efficacy outcome was the change in the response to a DBPC food challenge (DBPCFC) with peach. Secondary efficacy outcomes were the changes in skin prick test (SPT), and in specific immunoglobulin E (IgE) and IgG4 to Pru p 3. Tolerance was assessed with a careful recording of adverse events.Results:  After 6 months of SLIT, the active group tolerated a significantly higher amount of peach (three‐ to ninefold), presented a significant decrease (5.3 times) in SPT, and a significant increase in IgE and IgG4 to Pru p 3. No significant changes were observed within the placebo group. Statistically significant inter‐group differences were only observed in the SPT and IgG4 responses. No serious adverse events were reported. Systemic reactions were mild, and observed with a similar frequency in both groups. Local reactions were significantly more frequent in the active group (three times) and 95% of them restricted to the oral cavity.Conclusion:  In this first exploratory clinical trial, SLIT for peach allergy seems to be a promising therapeutic option that could modify the clinical reactivity of the patients to peach intake and the underlying immunological response with a good tolerance.
Evidence of heterogeneity in the antibody response against the platelet antigen 3a; recognition of an 11‐mer peptide carrying the HPA‐3a polymorphic determinant
Authors: De Leon E. J. , Yuan F‐F. , Pearson H. , Marquis C. P. , Mahler S. M. 
Published: January 2009

Background  The immune processes involved in the development of alloantibodies against the human platelet antigens in alloimmune disorders remain unclear. Antibody recognition of the platelet antigens on their respective platelet glycoproteins has been shown to be dependent on glycoprotein conformation. Furthermore, the post‐translational modification of glycoproteins adds complexity to the alloantigenic determinants.Methods  Nine anti‐HPA‐3a sera along with several control sera were tested for reactivity to an 11‐mer peptide straddling the HPA‐3a/b polymorphism. Sera found to specifically recognize the 3a peptide were further assessed by platelet pre‐exposure and immunoblotting.Results  Three of the nine antisera were found to specifically recognize an 11‐mer synthetic 3a peptide by ELISA. Further analysis of all anti‐HPA‐3a sera by Western blot showed that only those reactive to the 3a peptide were able to bind both reduced and non‐reduced GPIIb.Conclusion  The results presented in this study provide the first known evidence for the identification of an antibody population capable of recognizing a linear and non‐glycosylated form of the HPA‐3a epitope.
Evaluation of FABP2 as candidate gene for a fatty acid composition QTL in porcine chromosome 8
Authors: Estellé J. , Mercadé A. , Pérez‐Enciso M. , Pena R.N. , Silió L. , Sánchez A. , Folch J.M. 
Published: January 2009

SummaryThe objective of this work was to analyse the porcine Fatty acid binding protein 2, intestinal (FABP2) gene as a candidate gene for a fatty acid composition quantitative trait loci (QTL) previously described on porcine chromosome 8 in an Iberian by Landrace F2 cross (IBMAP). Re‐sequencing of the porcine FABP2 gene in three Iberian and eight Landrace parental animals resulted in the identification of three single‐nucleotide polymorphisms, all of them localized in intron 1. The polymorphism FABP2:g.412T>C, localized in intron 1, and two additional microsatellites were genotyped in the IBMAP population in order to perform an association test of the FABP2 gene and to better define the QTL position previously described. Association analyses of the FABP2:g.412T>C with the fatty acid composition traits were not significant in simple association and marker‐assisted association tests, suggesting that the FABP2 region sequenced is not responsible for the QTL. However, the addition of three new markers to the pedigree allowed us to define the S0144–SW61 marker interval as the most likely QTL position, facilitating the future study of other candidate genes for this QTL.
The protein secretory pathway of Candida albicans
Authors: Fonzi William A. 
Published: January 2009

SummaryVirulence of the opportunistic pathogen, Candida albicans, relies on an assemblage of attributes. These include the secretion of hydrolytic enzymes, cell surface adhesins, morphological transition between yeast and hyphae, phenotypic switching and biofilm formation. These diverse features are united by their dependence on the protein secretory apparatus for expression. Although the secretory apparatus of C. albicans has been studied limitedly, it appears to conform to the well‐conserved eukaryotic system of vesicle‐mediated transport between intracellular compartments and the cell surface. Genome comparison with Saccharomyces cerevisiae, however, shows multiple differences whose functional significance is yet unstudied. A unique aspect of the secretory pathway of C. albicans is its structural, and perhaps functional, rearrangement in hyphal vs. yeast cells. This, and evidence of non‐conserved secretion mechanism(s), suggest that there is much fundamental knowledge to be derived from the analysis of secretion in C. albicans, which will be relevant to its ability to cause disease.
Cardiac outcomes of hydrops as a result of twin–twin transfusion syndrome treated with laser surgery
Authors: Gray Peter H , Ward Cameron , Chan Fung‐Yee 
Published: January 2009

Aim:  To determine cardiac outcomes of foetal hydrops as a result of twin–twin transfusion syndrome treated with laser surgery.Methods:  Hydrops identified in 16 recipient foetuses with twin–twin transfusion syndrome was treated with laser ablation surgery to anastomotic vessels. Prior to laser surgery, the foetuses were assessed by echocardiography for cardiac abnormalities and ventricular and valvular dysfunction. After delivery, echocardiography was performed on 15 of the 16 newborn infants.Results:  Foetal echocardiography indicated impaired biventricular function in the 16 hydropic foetuses. Five foetuses had little or no forward flow through the pulmonary valve, while four had pulmonary regurgitation. Following laser surgery performed at a mean of 22.9 weeks gestation, hydrops resolved in all cases. Delivery occurred at a mean of 33.6 weeks gestation. Post‐natal echocardiography revealed cardiac abnormalities in five neonates, of whom three had right ventricular outflow tract obstruction. One preterm infant with severe pulmonary stenosis died with intractable cardiac failure.Conclusion:  The majority of hydropic infants with twin–win transfusion syndrome have normal cardiac outcomes following intrauterine laser surgery. As up to one‐third may have cardiac abnormalities, cardiological monitoring is recommended during the first year of life.
Identification of five novel variants in the thiazide‐sensitive NaCl co‐transporter gene in Chinese patients with Gitelman syndrome
Authors: QIN LING , SHAO LEPING , REN HONG , WANG WEIMING , PAN XIAOXIA , ZHANG WEN , WANG ZHAOHUI , SHEN PINGYAN , CHEN NAN 
Published: January 2009

SUMMARYAim:  Gitelman syndrome (GS) is an autosomal recessive renal tubulopathy characterized by hypokalaemic metabolic alkalosis, significant hypomagnesemia, low urinary calcium, secondary aldosteronism and normal blood pressure. GS is caused by inactivating variants in the SLC12A3 gene, which encodes the thiazide‐sensitive NaCl co‐transporter. So far, more than 100 variants have been described in the SLC12A3 gene in Gitelman syndrome.Methods:  Biochemical parameters in blood and urine were measured and documented. Genomic DNA was extracted from peripheral blood of all patients. Variants were screened for the SLC12A3 and CLCNKB gene by sequencing directly. Reverse‐transcription polymerase chain reaction and complementary DNA sequence analysis were performed to confirm deletion or splicing variants.Results:  We identified 13 variants in the SLC12A3 gene in 13 Chinese patients, including 10 missense substitutions, two splicing variants, and one deletion/insertion variant. Five novel variants were identified for the first time in patients with Gitelman syndrome. We did not find any variants in the CLCNKB gene. A homozygous Thr60Met carrier suffered from hypothyroidism and received thyroxine replacement therapy.Conclusion:  We have identified 13 variants, including five novel variants in the SLC12A3 gene in 13 patients with Gitelman syndrome. T60M is the most frequent variant in our patients. There was no significant correlation between genotype and phenotype in our patients.
Inactivation of mismatch repair increases the diversity of Vibrio parahaemolyticus
Authors: Hazen Tracy H. , Kennedy K. Danielle , Chen Shen , Yi Soojin V. , Sobecky Patricia A. 
Published: January 2009

SummaryInactivation of mismatch repair (MMR) has been shown to increase the accumulation of spontaneous mutations and frequency of recombination for diverse pathogenic bacteria. Currently, little is known regarding the role of mutator phenotypes for the diversification of natural populations of opportunistic human pathogens in marine environments. In this study, a higher frequency of mutators was detected among V. parahaemolyticus strains obtained from environmental sources compared with clinical sources. Inactivation of the MMR gene mutS caused increased antibiotic resistance and phase variation resulting in translucent colony morphologies. Increased nucleotide diversity in mutS and rpoB alleles from mutator compared with wild‐type strains indicated a significant contribution of the mutator phenotype to the evolution of select genes. The results of this study indicate that the inactivation of MMR in V. parahaemolyticus leads to increased genetic and phenotypic diversity. This study is the first to report a higher frequency of natural mutators among Vibrio environmental strains and to provide evidence that inactivation of MMR increases the diversity of V. parahaemolyticus.
Insulin therapy in type 2 diabetes: what is the evidence?
Authors: Van Avendonk Mariëlle J. P. , Rutten Guy E. H. M 
Published: January 2009

Aim:  To systematically review the literature regarding insulin use in patients with type 2 diabetes mellitusMethods:  A Medline and Embase search was performed to identify randomized controlled trials (RCT) published in English between 1 January 2000 and 1 April 2008, involving insulin therapy in adults with type 2 diabetes mellitus. The RCTs must comprise at least glycaemic control (glycosylated haemoglobin (HbA1c), postprandial plasma glucose and /or fasting blood glucose (FBG)) and hypoglycaemic events as outcome measurements.Results:  The Pubmed search resulted in 943 hits; the Embase search gave 692 hits. A total of 116 RCTs were selected by title or abstract. Eventually 78 trials met the inclusion criteria. The studies were very diverse and of different quality. They comprised all possible insulin regimens with and without combination with oral medication. Continuing metformin and/or sulphonylurea after start of therapy with basal long‐acting insulin results in better glycaemic control with less insulin requirements, less weight gain and less hypoglycaemic events. Long‐acting insulin analogues in combination with oral medication are associated with similar glycaemic control but fewer hypoglycaemic episodes compared with NPH insulin. Most of the trials demonstrated better glycaemic control with premix insulin therapy than with a long‐acting insulin once daily, but premix insulin causes more hypoglycaemic episodes. Analogue premix provides similar HbA1c, but lower postprandial glucose levels compared with human premix, without increase in hypoglycaemic events or weight gain. Drawing conclusions from the limited number of studies concerning basal–bolus regimen seems not possible. Some studies showed that rapid‐acting insulin analogues frequently result in a better HbA1c or postprandial glucose without increase of hypoglycaemia than regular human insulin.Conclusion:  A once‐daily basal insulin regimen added to oral medication is an ideal starting point. All next steps, from one to two or even more injections per day should be taken very carefully and in thorough deliberation with the patient, who has to comply with such a regimen for many years.
A population‐based comparison of survival after nephrectomy vs nonsurgical management for small renal masses
Authors: Zini Laurent , Perrotte Paul , Jeldres Claudio , Capitanio Umberto , Duclos Alain , Jolivet‐Tremblay Martine , Arjane Philippe , Péloquin François , Pharand Daniel , Villers Arnauld , Montorsi Francesco , Patard Jean‐Jacques , Karakiewicz Pierre I. 
Published: January 2009

OBJECTIVETo examine population‐based rates of cancer‐specific and other‐cause mortality after either non‐surgical management (NSM) or nephrectomy, in patients with small renal masses, as several reports from selected institutions support the applicability of surveillance in patients with small renal masses, but there are no population‐based studies confirming the general applicability of this therapy.PATIENTS AND METHODSOf 43 143 patients with renal cell carcinoma identified in the 1988–2004 Surveillance, Epidemiology and End Results database, 10 291 had localized small renal masses (≤4 cm) and were offered NSM (433, 4.2%) or nephrectomy (9858, 95.8%). Univariable matched and multivariable unmatched competing‐risks regression models were used in the analyses.RESULTSCumulative incidence plots based on unmatched data, where the effect of other‐cause mortality was controlled for, showed a 5.2%, 6.5% and 9.4% survival benefit for nephrectomy vs NSM at 1, 2 and 5 years after nephrectomy or diagnosis, respectively. The same magnitude of the benefit (4.5%, 5.6% and 8.0%) persisted in analyses matched for age, tumour size and year of diagnosis or of nephrectomy. Finally, in multivariable analyses, treatment type, age, tumour size and year of diagnosis or of nephrectomy were independent predictors.CONCLUSIONRelative to nephrectomy, NSM appears to undermine the overall and cancer‐specific survival of patients with small renal masses by as much as 9.4%, at 5 years.
CAN THERE BE A KANTIAN CONSEQUENTIALISM?
Authors: Morgan Seiriol 
Published: January 2009

AbstractIn On What Matters Derek Parfit argues that we need to make a significant reassessment of the relationship between some central positions in moral philosophy, because, contrary to received opinion, Kantians, contractualists and consequentialists are all ‘climbing the same mountain on different sides’. In Parfit's view Kant's own attempt to outline an account of moral obligation fails, but when it is modified in ways entirely congenial to his thinking, a defensible Kantian contractualism can be produced, which survives the objections which are fatal for Kant's own theory. This form of contractualism would then lead rational agents to choose consequentialist moral principles. I argue that Parfit significantly misrepresents Kant's project in moral philosophy, and that no genuinely Kantian moral theory could issue in a form of consequentialism.
CLIMB EVERY MOUNTAIN?
Authors: Ridge Michael 
Published: January 2009

AbstractThe central thesis of Derek Parfit's On What Matters is that three of the most important secular moral traditions – Kantianism, contractualism, and consequentialism – all actually converge in a way onto the same view. It is in this sense that he suggests that we may all be ‘climbing the same mountain, but from different sides’. In this paper, I argue that Parfit's argument that we are all metaphorically climbing the same mountain is unsound. One reason his argument does not work is that he has misunderstood the way in which a plausible rule‐consequentialism should understand the supervenience of rightness on all possible acceptance levels of the ideal moral code. In place of Parfit's own understanding of this, I develop a view I call ‘variable‐rate rule‐utilitarianism’, which I argue shares the key insight of Parfit's view but avoids a fatal objection to his own articulation of that insight. Finally, I explore how this modification might allow us to still make a case that we are all ‘climbing the same mountain’, albeit in a very different way and for very different reasons than the ones Parfit had in mind.
DESIRES, VALUES, REASONS, AND THE DUALISM OF PRACTICAL REASON
Authors: Smith Michael 
Published: January 2009

AbstractIn On What Matters Derek Parfit argues that facts about reasons for action are grounded in facts about values and against the view that they are grounded in facts about the desires that subjects would have after fully informed and rational deliberation. I describe and evaluate Parfit's arguments for this value‐based conception of reasons for action and find them wanting. I also assess his response to Sidgwick's suggestion that there is a Dualism of Practical Reason. Parfit seems not to notice that his preferred value‐based conception of reasons for action augurs strongly in favour of a view like Sidgwick's.1
WAGE DIFFERENTIALS, DISCRIMINATION AND INEQUALITY: A CAUTIONARY NOTE ON THE JUHN, MURPHY AND PIERCE DECOMPOSITION METHOD
Authors: Yun Myeong‐Su 
Published: January 2009

ABSTRACTThis paper shows how difficult it is to study the roles of discrimination and unobserved skills when studying changes in racial and gender wage gaps over time by examining merits and shortcomings of a popular decomposition method by Juhn, Murphy and Pierce (JMP). The JMP method shows that wage dispersion can offer a compelling explanation of the wage gap. However, JMP have to rely on a few strong assumptions in order to derive their decomposition equation, which introduces wage inequality as the price of unobserved skills (the standard deviation of the residuals) into their decomposition equation.
Time, self and the medication day: a closer look at the everyday work of ‘adherence’
Authors: McCoy Liza 
Published: January 2009

AbstractThis article examines the everyday work of participating in pharmaceutical treatment for HIV infection in the context of urgent calls for adherence. Drawing on interviews and focus‐group conversations with people taking antiretroviral drugs, the analysis explicates the work that goes into striving for adherence. What comes into view is a form of time work that brings about a temporary alignment between the inner experience of time, standard clock time, and the requirements of the medication schedule. Time work is largely cognitive; the pills, however, must actually be swallowed to complete the dose, occasioning, for some people, additional work to suppress or refashion emotional responses of anger and resistance. Both the time work and the emotional work of taking antiretroviral drugs draw people into forms of self work, including self‐examination and self‐adjustment, as they develop strategies for ‘doing adherence’.
Using BayesianP-Values in a 2 × 2 Table of Matched Pairs with Incompletely Classified Data
Authors: Lin Yan , Lipsitz Stuart , Sinha Debajyoti , Gawande Atul A. , Regenbogen Scott E. , Greenberg Caprice C. 
Published: January 2009

SummaryAltham proposed Bayesian p-values for the analysis of a 2×2 contingency table that is formed from matched pairs. Using the same Bayesian perspective, we develop an extension of Altham’s Bayesian p-values to a 2×2 table from matched pairs with missing data that are missing at random. The approach is applied to a rater agreement study, in which two surgeon–reviewers rated whether or not there was a communication breakdown in malpractice cases. We also use a simulation study to explore the power and type I error rate of the Bayesian p-values.
The Radial Plot in Meta-Analysis: Approximations and Applications
Authors: Copas John , Lozada-Can Claudia 
Published: January 2009

Summary
Fixed effects meta-analysis can be thought of as least squares analysis of the radial plot, the plot of standardized treatment effect against precision (reciprocal of the standard deviation) for the studies in a systematic review. For example, the least squares slope through the origin estimates the treatment effect, and a widely used test for publication bias is equivalent to testing the significance of the regression intercept. However, the usual theory assumes that the within-study variances are known, whereas in practice they are estimated. This leads to extra variability in the points of the radial plot which can lead to a marked distortion in inferences that are derived from these regression calculations. This is illustrated by a clinical trials example from the Cochrane database. We derive approximations to the sampling properties of the radial plot and suggest bias corrections to some of the commonly used methods of meta-analysis. A simulation study suggests that these bias corrections are effective in controlling levels of significance of tests and coverage of confidence intervals.
The oxygen status of the developing seed
Authors: Borisjuk Ljudmilla , Rolletschek Hardy 
Published: January 2009

SummaryRecent applications of oxygen‐sensitive microsensors have demonstrated steep oxygen gradients in developing seeds of various crops. Here, we present an overview on oxygen distribution, major determinants of the oxygen status in the developing seed and implications for seed physiology. The steady‐state oxygen concentration in different seed tissues depends on developmental parameters, and is determined to a large extent by environmental factors. Photosynthetic activity of the seed significantly diminishes hypoxic constraints, and can even cause transient, local hyperoxia. Changes in oxygen availability cause rapid adjustments in mitochondrial respiration and global metabolism. We argue that nitric oxide (NO) is a key player in the oxygen balancing process in seeds, avoiding fermentation and anoxia in vivo. Molecular approaches aiming to increase oxygen availability within the seed are discussed.

Contents

Summary
17

I.
Introduction
17

II.
Oxygen diffusion and the barriers to gas exchange
18

III.
Metabolic indicators of seed hypoxia
19

IV.
High‐resolution mapping of oxygen distribution in the developing seed
20

V.
The effect of environmental factors on steady‐state oxygen concentrations
23

VI.
Gene expression and metabolism under low oxygen
24

VII.
Mechanisms of oxygen sensing and balancing in seeds
25

VIII.
Might low internal oxygen levels be advantageous for seed development?
27

Acknowledgements
27

References
28