bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Characterization of Patients with X‐linked Hyper‐IgM Syndrome: Description of Two Novel CD40L Mutations
Authors: Rangel‐Santos A. , Wakim V. L. , Jacob C. M. , Pastorino A. C. , Cunha J. M. , Collanieri A. C. , Niemela J. E. , Grumach A. S. , Duarte A. J. S. , Moraes‐Vasconcelos D. , Oliveira J. B.
Published: January 2009

Type 1, X‐linked Hyper‐IgM syndrome (HIGM1) is caused by mutations in the gene encoding the CD154 protein, also known as CD40 ligand (CD40LG). CD40L is expressed in activated T cells and interacts with CD40 receptor expressed on B lymphocytes and dendritic cells. Affected patients present cellular and humoral immune defects, with infections by intracellular, opportunistic and extracellular pathogens. In the present study we investigated the molecular defects underlying disease in four patients with HIGM1. We identified four distinct CD40L mutations, two of them which have not been previously described. P1 harboured the novel p.G227X mutation which abolished CD40L expression. P2 had a previously described frame shift deletion in exon 2 (p.I53fsX65) which also prevented protein expression. P3 demonstrated the previously known p.V126D change in exon 4, affecting the TNF homology (TNFH) domain. Finally, P4 evidenced the novel p.F229L mutation also located in the TNFH domain. In silico analysis of F229L predicted the change to be pathological, affecting the many hydrophobic interactions of this residue. Precise molecular diagnosis in HIGM syndrome allows reliable detection of carriers, making genetic counselling and prenatal diagnosis possible.
Phylogeny and biogeography ofCoenonymphabutterflies (Nymphalidae: Satyrinae) – patterns of colonization in the Holarctic
Authors: KODANDARAMAIAH ULLASA , WAHLBERG NIKLAS
Published: January 2009

AbstractWe studied the historical biogeography of a group of butterflies in the Holarctic region belonging to the genusCoenonympha(Nymphalidae: Satyrinae: Coenonymphina), based on a phylogenetic hypothesis estimated from three genes. The genus is distributed mainly in the Palaearctic region, with two species extending into the Nearctic region. The tree is generally well supported and shows thatCoenonymphais paraphyletic with respect toLyela(syn.n.) andTriphysa(syn.n.), and we hence synonymize the latter two withCoenonympha. WithinCoenonymphawe identify three species groups, thetullia,glycerionandherogroups. The North Americantulliaexemplars are not sister to the Eurasian ones. A diva analysis indicates that the ancestor of the group was present in the Central Palaearctic or Central Palaeartic + Western Palaearctic or Central Palaearctic + Eastern Palaearctic. We conclude that the most likely origin of extant members ofCoenonymphawas in the Central Asian mountains. Thetulliaandherogroups started diverging in Europe following dispersal into the region. There have been two independent colonizations into Africa. The drying up of the Mediterranean during the Messinian period probably played an important role, allowing colonization into the Mediterranean islands and Africa.
The Neotropical genus Stibadocerina Alexander and its phylogenetic relationship to other Stibadocerinae genera: further evidence of an ancestral trans‐Pacific biota (Diptera: Cylindrotomidae)
Authors: RIBEIRO GUILHERME C
Published: January 2009

Abstract Stibadocerina Alexander, a monotypic genus, includes the only known Neotropical species of the family Cylindrotomidae, S. chilensis Alexander, 1929, from South Central Chile (ca. 36°50′S–42°17′S). In this paper, Stibadocerina chilensis is redescribed and illustrated in detail. A study of wing‐vein homology in the subfamily Stibadocerinae is provided, to identify the components of the reduced radial sector in Stibadocerina and related taxa. The proposed hypotheses of wing‐vein homology are tested, and the systematic position of Stibadocerina is assessed through a cladistic analysis of 13 characters of the male imago, scored for exemplar species of the four genera included in the Stibadocerinae. A single most parsimonious tree supports the monophyly of the Stibadocerinae and the following relationships among its included genera: Stibadocerodes [Stibadocera (Stibadocerella +Stibadocerina)]. The subfamily includes one example of a vicariant distribution with a sister‐group relationship between South Central Chilean and East Asian taxa, and supports a biogeographical interpretation of an ancestral trans‐Pacific biota.
Critical care in low‐income countries
Authors: Baker Tim
Published: January 2009

Critical care in low‐income countries remains rudimentary. When defined as all aspects of care for patients with sudden, serious, reversible disease, critical care is not disease or age specific and includes triage and emergency medicine, hospital systems, quality of care and Intensive Care Units. This review collates the literature on critical care in low‐income countries and explores how the care can be both feasible and effective. Emergency care including triage is often one of the weakest parts of the health system; but if well organized it can be life‐saving and cost‐effective. Emergency triage and treatment has been developed for paediatric admissions with promising results. Hospital systems do not currently prioritize the critically ill and few hospitals have Intensive Care Units. The quality of care given to inpatients on hospital wards is often poor and could be improved in many ways. There is a lack of training and awareness of the principles of critical care. Basic critical care concentrating on ABC – airway, breathing and circulation – need not be resource intensive. Oxygen is a cheap and effective treatment for pneumonia and other severe disease, but is not always available. Improved critical care could have a significant effect on the burden of disease and effects of ill health. Research into the most cost‐effective treatments and methods of caring for critically ill patients is urgently needed.
Adherence rate to inhaled corticosteroids and their impact on asthma control
Authors: Lasmar L. , Camargos P. , Champs N. S. , Fonseca M. T. , Fontes M. J. , Ibiapina C. , Alvim C. , Moura J. A. R.
Published: January 2009

Background:  Poor asthma control is associated to high morbidity. The objective of this study was to assess the association between adherence rates to beclomethasone dipropionate (BDP) and the degree of asthma control.

Methods:  A cohort concurrent study was carried out for 12 months with 122 asthmatic patients, aged 3–12 years, randomly selected in a pediatric pulmonology outpatient clinic, who received BDP free of charge. Adherence rates were verified by pharmacy records. Clinical control was assessed through a scoring system comprised four variables (nocturnal and morning symptoms, limitation of physical activities and exacerbations). Total score was 16 points. Patients whose score was below or equal to two were considered controlled (group 1), and patients whose score was above or equal to three were considered uncontrolled (group 2). For patients able to perform spirometry, we considered as controlled the patients with forced expiratory volume in 1 s (FEV1) equal to or above 80% of the predicted value, and as uncontrolled the patients with FEV1 below 80%.

Results:  Fewer than half (40.3% maximum) of the 122 patients maintained asthma control. Median adherence rate of groups 1 and 2 were 85.5% and 33.8%, (P < 0.001) in the 4th month, 90.0% and 48.0% (P < 0.001) in the 8th month and 84.4% and 47.0% in the 12th month (P < 0.001), respectively.

Conclusion:  In all periods, there were statistically significant differences in adherence rates for maintaining or not maintaining the asthma control. Optimal asthma control entailed adherence rate higher than 80%. Strategies for reducing asthma morbidity should include a regular monitoring of adherence to inhaled steroids.
Time trends in prevalence and severity of childhood asthma and allergies from 1995 to 2002 in France
Authors: Annesi‐Maesano I. , Mourad C. , Daures J.‐P. , Kalaboka S. , Godard P.
Published: January 2009

Objective:  To assess time trends in symptoms of asthma, allergic rhinitis and atopic eczema among adolescents in Languedoc Roussillon, France.

Methods:  Two cross‐sectional surveys were conducted 7 years apart using the same protocol. School‐based samples of 3383 participants in the 1995 survey and 1642 participants in the 2002 survey respectively were recruited.

Results:  There was a tendency towards stagnation in current symptoms of asthma, rhinoconjunctivitis and eczema. Indices related to lifetime diagnosis of asthma, hay fever and eczema increased. For all the conditions, indices of severity also showed a decrease in the 7‐year study period.

Conclusions:  Our study shows that symptoms of asthma, allergic rhinitis and eczema were stable, supporting the effectiveness of national asthma prevention and management guidelines for such diseases. The increase in indices related to lifetime diagnosis could be the result of increased public and professional awareness of the diseases and changes in diagnostic labelling in recent years.
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

The 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

Virulence 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

Aim:  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

Inactivation 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 mellitus

Methods:  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

OBJECTIVE

To 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 METHODS

Of 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.

RESULTS

Cumulative 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.

CONCLUSION

Relative 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.
AN EMPIRICAL ANALYSIS OF CHILD CARE DEMAND IN SWITZERLAND
Authors: Banfi Silvia , Farsi Mehdi , Filippini Massimo
Published: January 2009

ABSTRACT**:  This paper analyzes the demand of Swiss families for child care facilities. A choice experiment is used to study the effects of the facilities' characteristics as well as socio‐economic factors on the selected child care mode. The experimental data are analyzed using a discrete choice model with multinomial logit specification. The results suggest that the demand for extra‐familial day care could be considerably higher than that observed from the actual choices constrained by insufficient provision of affordable day care. The price, access, and the quality of service as well as parents' income and education have important impacts on the choice of the mode of care.
THE RELATIVE EFFICIENCY OF CHARTER SCHOOLS
Authors: Grosskopf Shawna , Hayes Kathy J. , Taylor Lori L.
Published: January 2009

ABSTRACT**:  This analysis compares the technical efficiency of charter school primary and secondary campuses with that of comparable campuses in traditional Texas school districts. Charter schools are hybrids—publicly funded, but not required to meet all the state regulations releant for traditional schools. Student performance is measured using value added on standardized tests in reading and mathematics, and efficiency is measured using the input distance function. The analysis suggests that at least in Texas, charter schools are substantially more efficient than traditional public schools.
Existential function of babies: Babies as a buffer of death‐related anxiety
Authors: Zhou Xinyue , Lei Qijia , Marley Scott C. , Chen Jinsong
Published: January 2009

The present study examined babies as death anxiety buffers with Chinese participants in three experiments. In Experiment 1, death‐related thoughts increased college‐aged participants' interest in human babies. In Experiment 2, images of newborn animals reduced the number of death‐related thoughts recorded by college‐aged participants. In Experiment 3, female factory workers who read news articles describing deaths of babies had pessimistic estimations of their own life expectancies. An explanation of these results is provided within a terror management theory framework, with a primary focus on how babies reinforce cultural worldviews and enhance self‐esteem via the notion of symbolic immortality. Thus, the anxiety‐buffering function of baby is subsumed under cultural worldviews validation and self‐esteem enhancement.
CAN THERE BE A KANTIAN CONSEQUENTIALISM?
Authors: Morgan Seiriol
Published: January 2009

In 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

The 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

In 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

This 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

This 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

Altham 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

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

Recent 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
What does ‘inclusion’ mean for pupils on the autistic spectrum in mainstream secondary schools?
Authors: Humphrey Neil , Lewis Sarah
Published: January 2009

The last decade has seen a groundswell of developments in educational policy in the UK relating to inclusive education for students with special educational needs (SEN). However, whether government policy has been fully implemented in schools remains a concern. The experience of students with autistic spectrum disorders (ASDs) provides an excellent case in point. An increasing number of such students are now educated in mainstream schools, but the limited research in this area has indicated that their experience of school is often marked by bullying, social isolation and anxiety. In light of this, the aim of the current study was to examine the extent to which inclusive educational policy was actually reflected in the practices of four mainstream secondary schools. An exploratory case study approach was adopted, utilising interviews with pupils, teachers, other school staff (e.g., senior managers, learning support assistants) and parents, observations of lessons and other contexts (e.g., lunch time), and document analysis. Our findings highlighted a number of school practices which acted as facilitators or barriers to students’ learning and participation, some of which were generic to SEN provision, and some of which appeared to be specific to those on the autistic spectrum. A discussion of these is presented to enable further understanding of, and inform practice relating to, the inclusion process for students with ASDs.
Altered CB1receptor‐signaling in prefrontal cortex from an animal model of depression is reversed by chronic fluoxetine
Authors: Rodríguez‐Gaztelumendi Antonio , Rojo Mª Luisa , Pazos Angel , Díaz Alvaro
Published: January 2009

Bilateral olfactory bulbectomy in the rat (OBX) induces behavioral, neurochemical, and structural abnormalities similar to those observed in human depression that are normalized after chronic, but not acute, treatment with antidepressants. In our study, OBX animals exhibited significant increases in both CB1receptor density ([3H]CP55490 binding) and functionality (stimulation of [35S]GTPγS binding by the cannabinoid (CB) agonist WIN 55212‐2) at the prefrontal cortex (PFC). After chronic treatment with fluoxetine (10 mg/kg/day, 14 days, s.c.), OBX‐induced hyperactivity in the open‐field test was fully abolished. Interestingly, chronic fluoxetine fully reversed the enhanced CB1‐receptor signaling in PFC observed following OBX. The CB agonist Δ9‐tetrahydrocannabinol (5 mg/kg, i.p., 1 day) did not produce any behavioral effect in sham‐operated animals but returned locomotor activity to control values in OBX rats. As both acute administration of Δ9‐tetrahydrocannabinol and chronic fluoxetine elicited a similar behavioral effect in the OBX rat, it is not unlikely that the regionally selective enhancement of CB1receptor‐signaling in the PFC could be related with the altered OBX behavior. Our findings reinforce the utility of this animal model to further investigating the implication of the endocannabinoid system in the modulation of emotional processes and its potential role in the adaptive responses to chronic antidepressants.
Curcumin, quercetin, and tBHQ modulate glutathione levels in astrocytes and neurons: importance of the glutamate cysteine ligase modifier subunit
Authors: Lavoie Suzie , Chen Ying , Dalton Timothy P. , Gysin René , Cuénod Michel , Steullet Pascal , Do Kim Q.
Published: January 2009

A decrease in GSH levels, the main redox regulator, can be observed in neurodegenerative diseases as well as in schizophrenia. In search for substances able to increase GSH, we evaluated the ability of curcumin (polyphenol), quercetin (flavonoid), and tert‐butylhydroquinone (tBHQ) to up‐regulate GSH‐synthesizing enzymes. The gene expression, activity, and product levels of these enzymes were measured in cultured neurons and astrocytes. In astrocytes, all substances increased GSH levels and the activity of the rate‐limiting synthesizing enzyme, glutamate cysteine ligase (GCL). In neurons, curcumin and to a lesser extent tBHQ increased GCL activity and GSH levels, while quercetin decreased GSH and led to cell death. In the two cell types, the gene that showed the greatest increase in its expression was the one coding for the modifier subunit of GCL (GCLM). The increase in mRNA levels of GCLM was 3 to 7‐fold higher than that of the catalytic subunit. In astrocytes from GCLM‐knock‐out mice showing low GSH (−80%) and low GCL activity (−50%), none of the substances succeeded in increasing GSH synthesis. Our results indicate that GCLM is essential for the up‐regulation of GCL activity induced by curcumin, quercetin and tBHQ.
Angiotensin‐(1–7) through AT2receptors mediates tyrosine hydroxylase degradation via the ubiquitin–proteasome pathway
Authors: Lopez Verrilli María A. , Pirola Carlos J. , Pascual Mariano M. , Dominici Fernando P. , Turyn Daniel , Gironacci Mariela M.
Published: January 2009

Hypothalamic norepinephrine (NE) release regulates arterial pressure by altering sympathetic nervous system activity. Because angiotensin (Ang) (1–7) decreases hypothalamic NE release and this effect may be correlated with a diminished NE synthesis, we hypothesize that Ang‐(1–7) down‐regulates tyrosine hydroxylase (TH), the rate‐limiting enzyme in catecholamines biosynthesis. We investigated the effect of Ang‐(1–7) on centrally TH activity and expression. TH activity was evaluated by the release of tritiated water from3H‐l‐tyrosine. TH expression and phosphorylation were determined by western blot. Hypothalami from normotensive or spontaneously hypertensive rats pre‐incubated with Ang‐(1–7) showed a significant decrease in TH specific activity. Ang‐(1–7) caused a decrease in TH phosphorylation at Ser19 and Ser40 residues. The heptapeptide induced a decrease in TH expression that was blocked by an AT2receptor antagonist and not by an AT1or Mas receptor antagonist, suggesting the involvement of AT2receptors. The proteasome inhibitor MG132 blocked the Ang‐(1–7)‐mediated TH reduction. In addition, Ang‐(1–7) increased the amount of TH–ubiquitin complexes, indicating that the Ang‐(1–7)‐mediated TH degradation involves ubiquitin conjugation prior to proteasome degradation. We conclude that Ang‐(1–7) down‐regulates TH activity and expression centrally leading to a decrease in the central NE system activity.
The experience of caring in relatives to patients with serious mental illness: gender differences, health and functioning
Authors: Møller Turid , Gudde Camilla Buch , Folden Gunn Eva , Linaker Olav M.
Published: January 2009

The aims of the study were twofold. First, the study examined the extent to which there are gender differences in the experience of caring in a sample of relatives of patients with serious mental illness. Secondly, the study examined the association of self‐reports of health and functioning with the experience of burden among relatives of patients with serious mental illness. A total of 50 relatives of 32 patients receiving psychiatric treatment for their bipolar or psychotic condition completed the Experience of Caregiving Inventory (ECI) and COOP‐WONCA (a self‐report measure of general state of health and functioning). The study revealed that female relatives had a higher score on eight of 10 ECI subscores, and in both ECI negative and ECI positive. Additionally, the study revealed significant correlations between a higher score on the COOP‐WONCA feeling subscore and the following ECI subscores: stigma (r = 0.304, p < 0.05), problem with services (r = 0.348, p < 0.05), need to back up (r = 0.335, p < 0.05), loss (r = 0.293, p < 0.05) and the total ECI negative subscore (r = 0.343, p < 0.05). We also found a significant correlation between a higher score on the overall health subscore (COOP‐WONCA) and a higher score on problems with services (r = 0.290, p < 0.05). Gender was the strongest predictor of the ECI negative subscore. Neither the COOP‐WONCA subscore physical health, daily activities or social activities correlated significantly with any of the ECI subscores. Our results showed strong associations between poor mental well‐being and caregiver burden. We also found a higher association with gender and the feelings subscore (COOP‐WONCA) on ECI negative than we had expected.
Slope of the Out‐of‐Plane Deflection Measurement of Composite Sandwich Plate With a Fully Potted Insert by Using Digital Phase‐Shifting Shearography
Authors: Huang S.‐J. , Liu Y.‐F.
Published: January 2009

Abstract:  A digital shearographic (DS) technique is a tool well‐suited for precision strain measurement and is a non‐destructive testing technology. But the fringe patterns of DS have not so high sensitivity due to the limitation of CCD camera resolution. Therefore a phase‐shifting technique is incorporated into DS and demonstrated to yield fringe patterns with good quality. The main purpose of this study is to set‐up a measuring system of digital phase‐shifting shearography (DPSS) to measure slope of the out‐of‐plane deflection of sandwich plate with a fully potted insert. The present system includes piezoelectric transducer, servo controller, Michelson shearing mechanism, image processing system and loading system. The four‐step phase shifting method is used to obtain phase map and then the phase expansion is proceeded by Macy algorithm to obtain the slope of the out‐of‐plane deflection of honeycomb sandwich plate with insert/potting material. Finally, comparing the slope of the out‐of‐plane deflection of DPSS with that of DS shows 2 to 7% difference of slope of deflection exhibiting.
Patch‐Occupancy Modeling as a Method for Monitoring Changes in Forest Floristics: a Case Study in Southeastern Australia
Authors: PENMAN TRENT D. , BINNS DOUG L. , KAVANAGH RODNEY P.
Published: January 2009

Abstract:  The ability to monitor changes in biodiversity is fundamental to demonstrating sustainable management practices of natural resources. Disturbance studies generally focus on responses at the plot scale, whereas landscape‐scale responses are directly relevant to the development of sustainable forest management. Modeling changes in occupancy is one way to monitor landscape‐scale responses. We used understory vegetation data collected over 16 years from a long‐term study site in southeastern Australia. The site was subject to timber harvesting and frequent prescribed burning. We used occupancy models to examine the impacts of these disturbances on the distribution of 50 species of plants during the study. Timber harvesting influenced the distribution of 9 species, but these effects of harvesting were generally lost within 14 years. Repeated prescribed fire affected 22 species, but the heterogeneity of the burns reduced the predicted negative effects. Twenty‐two species decreased over time independent of treatment, and only 5 species increased over time. These changes probably represent a natural response to a wildfire that occurred in 1973, 13 years before the study began. Occupancy modeling is a useful and flexible technique for analyzing monitoring data and it may also be suitable for inclusion within an adaptive‐management framework for forest management.
Adjunctive lacosamide for partial‐onset seizures: Efficacy and safety results from a randomized controlled trial
Authors: Halász Péter , Kälviäinen Reetta , Mazurkiewicz‐Beldzińska Maria , Rosenow Felix , Doty Pamela , Hebert David , Sullivan Timothy ,   on behalf of the SP755 Study Group
Published: January 2009

Purpose:  To evaluate the efficacy and safety of lacosamide (200 and 400 mg/day) when added to one to three concomitant antiepileptic drugs (AEDs) in patients with uncontrolled partial‐onset seizures.

Methods:  This multicenter, double‐blind, placebo‐controlled trial randomized patients (age 16–70 years) with partial‐onset seizures with or without secondary generalization to placebo, lacosamide 200, or lacosamide 400 mg/day. The trial consisted of an 8‐week baseline, a 4‐week titration, and a 12‐week maintenance period.

Results:  Four hundred eighty‐five patients were randomized and received trial medication. Among these, 87% were taking two or more concomitant AEDs. Median percent reduction in seizure frequency per 28 days from baseline to maintenance period (intent‐to‐treat, ITT) was 20.5% for placebo, 35.3% for lacosamide 200 mg/day (p = 0.02), and 36.4% for 400 mg/day (p = 0.03). In the per protocol population, the reductions were 35.3% for lacosamide 200 mg/day (p = 0.04) and 44.9% for 400 mg/day (p = 0.01) compared to placebo (25.4%). The 50% responder rate for lacosamide 400 mg/day (40.5%) was significant (p = 0.01) over placebo (25.8%), but was not for 200 mg/day (35.0%). In the per protocol population, the 50% responder rate for lacosamide 400 mg/day (46.3%) was significant (p < 0.01) compared with the placebo responder rate (27.5%). Dose‐related adverse events (AEs) included dizziness, nausea, and vomiting. Clinically relevant changes in the mean plasma concentrations of commonly used AEDs were not observed.

Discussion:  Results of this trial demonstrated the efficacy and tolerability of adjunctive lacosamide 200 and 400 mg/day and support that lacosamide may be an advantageous option for the treatment of partial‐onset seizures in patients with epilepsy.