bluuebunny/crossref_metadata_2025 huggingface dataset:
Ancestral haplotype-based association mapping with generalized linear mixed models accounting for stratification
Authors: Zhang Z. , Guillaume F. , Sartelet A. , Charlier C. , Georges M. , Farnir F. , Druet T.
Published: June 2012

Motivation: In many situations, genome-wide association studies are performed in populations presenting stratification. Mixed models including a kinship matrix accounting for genetic relatedness among individuals have been shown to correct for population and/or family structure. Here we extend this methodology to generalized linear mixed models which properly model data under various distributions. In addition we perform association with ancestral haplotypes inferred using a hidden Markov model.

Results: The method was shown to properly account for stratification under various simulated scenari presenting population and/or family structure. Use of ancestral haplotypes resulted in higher power than SNPs on simulated datasets. Application to real data demonstrates the usefulness of the developed model. Full analysis of a dataset with 4600 individuals and 500 000 SNPs was performed in 2 h 36 min and required 2.28 Gb of RAM.

Availability: The software GLASCOW can be freely downloaded from www.giga.ulg.ac.be/jcms/prod_381171/software.

Contact:  francois.guillaume@jouy.inra.fr

Supplementary information:  Supplementary data are available at Bioinformatics online.
Combinatorial readout of unmodified H3R2 and acetylated H3K14 by the tandem PHD finger of MOZ reveals a regulatory mechanism for HOXA9 transcription
Authors: Qiu Yu , Liu Lei , Zhao Chen , Han Chuanchun , Li Fudong , Zhang Jiahai , Wang Yan , Li Guohong , Mei Yide , Wu Mian , Wu Jihui , Shi Yunyu
Published: June 2012

Histone acetylation is a hallmark for gene transcription. As a histone acetyltransferase, MOZ (monocytic leukemia zinc finger protein) is important for HOX gene expression as well as embryo and postnatal development. In vivo, MOZ forms a tetrameric complex with other subunits, including several chromatin-binding modules with regulatory functions. Here we report the solution structure of the tandem PHD (plant homeodomain) finger (PHD12) of human MOZ in a free state and the 1.47 Å crystal structure in complex with H3K14ac peptide, which reveals the structural basis for the recognition of unmodified R2 and acetylated K14 on histone H3. Moreover, the results of chromatin immunoprecipitation (ChIP) and RT–PCR assays indicate that PHD12 facilitates the localization of MOZ onto the promoter locus of the HOXA9 gene, thereby promoting the H3 acetylation around the promoter region and further up-regulating the HOXA9 mRNA level. Taken together, our findings suggest that the combinatorial readout of the H3R2/K14ac by PHD12 might represent an important epigenetic regulatory mechanism that governs transcription and also provide a clue of cross-talk between the MOZ complex and histone H3 modifications.
DAJUST: a suite of computer programs for pattern matching, space-group determination and intensity extraction from powder diffraction data
Authors: Vallcorba Oriol , Rius Jordi , Frontera Carlos , Peral Inma , Miravitlles Carles
Published: June 2012

DAJUSTis the generic name of a software package for powder diffraction formed by the core programsAJUSTandSGAID(both written in Fortran) controlled by an easy-to-use Java user interface (DAJUST_UI). WhileAJUSTperforms whole-pattern matching (cell-parameter refinement, profile fitting and intensity extraction),SGAIDprovides a list of the most probable space groups. For the extraction of the integrated intensities,AJUSTuses the Le Bail procedure but with a different formula for refining the integrated intensities. Laboratory, synchrotron X-ray and neutron sources, and both reflection and transmission experimental geometries, are supported. Other program options include automated background estimation, asymmetry correction, and corrections for absorption, variable divergence and/or illumination. The extracted intensity data are written in text format and can be directly processed by the direct methods programXLENS[Rius (2011).Acta Cryst.A67, 63–67] and the multisolution direct-space structure determination programTALP[Vallcorba, Rius, Frontera & Miravitlles (2011).Acta Cryst.A67, C272].
Ferroelectric domains in PZT ceramics at the morphotropic phase boundary. Can the splitting of reflections in SAED patterns be used for the distinction of different pseudo-cubic phases?
Authors: Schierholz Roland , Fuess Hartmut
Published: June 2012

Tetragonal, rhombohedral and monoclinic ferroelectric domains can all occur in morphotropic PbZr1−xTixO3(PZT) ceramics. In this article, the influence of these domains on the splitting of reflections in selected area electron diffraction (SAED) patterns along the main pseudo-cubic zone axes is reported. The orientation of the domain wall in a transmission electron microscopy image with respect to the splitting of reflections in the diffraction pattern has to be considered for the interpretation. The distinction of tetragonal and rhombohedral splitting is achieved for a pronounced splitting except for 〈111〉 with the domain wall edge on. As the monoclinic structure contains tetragonal as well as rhombohedral distortions, the distinction of monoclinic symmetry from tetragonal and rhombohedral based only on the splitting of reflections is not possible. Conceivable models of configurations of monoclinic subdomains inside the existing tetragonal or rhombohedral microdomains are derived from group–subgroup relations. Some experimental observations are given, which can only be explained by these models.
Mimicking the tumour microenvironment: three different co‐culture systems induce a similar phenotype but distinct proliferative signals in primary chronic lymphocytic leukaemia cells
Authors: Hamilton Emma , Pearce Laurence , Morgan Liam , Robinson Sophie , Ware Vicki , Brennan Paul , Thomas N. Shaun B. , Yallop Deborah , Devereux Stephen , Fegan Chris , Buggins Andrea G. S. , Pepper Chris
Published: June 2012

Interactions in the tumour microenvironment can promote chronic lymphocytic leukaemia (CLL) cell survival, proliferation and drug resistance. A detailed comparison of three co‐culture systems designed to mimic the CLL lymph node and vascular microenvironments were performed; two were mouse fibroblast cell lines transfected with human CD40LG or CD31 and the third was a human microvascular endothelial cell line, HMEC‐1. All three co‐culture systems markedly enhanced CLL cell survival and induced a consistent change in CLL cell phenotype, characterized by increased expression of CD38, CD69, CD44 and ITGA4 (CD49d); this phenotype was absent following co‐culture on untransfected mouse fibroblasts. In contrast to HMEC‐1 cells, the CD40LG and CD31‐expressing fibroblasts also induced ZAP70 expression and marked CLL cell proliferation as evidenced by carboxyfluorescein succinimidyl ester labelling and increased Ki‐67 expression. Taken together, our data show that co‐culture on different stroma induced a remarkably similar activation phenotype in CLL cells but only the CD40LG and CD31‐expressing fibroblasts increased ZAP70 expression and CLL cell proliferation, indicating that ZAP70 may play a critical role in this process. This comparative study reveals a number of striking similarities between the co‐culture systems tested but also highlights important differences that should be considered when selecting which system to use for in‐vitro investigations.
River macrophyte indices: not the Holy Grail!
Authors: DEMARS BENOÎT O. L. , POTTS JACQUELINE M. , TRÉMOLIÈRES MICHÈLE , THIÉBAUT GABRIELLE , GOUGELIN NATHALIE , NORDMANN VINCENT
Published: June 2012

1. Recent studies have demonstrated that there is generally no unambiguous relationship between plant species composition and specific environmental conditions in rivers. Nevertheless, indices of environmental pressures based on macrophytes are flourishing, because of the requirements of the Water Framework Directive (WFD).

2. We first reviewed nine such indices against 13 criteria for bioindicators. Then, using data from France and England, we tested whether the IBMR (Macrophyte Biological Index for Rivers) and LEAFPACS (predictions and classification system for macrophytes) methods could reliably indicate nutrient and hydromorphological pressures. Finally, we used an improved bootstrapping method to estimate accuracy.

3. Currently, most indices lack ecological meaning for a variety of reasons, including partial sampling (backwaters are excluded); reliance on list of taxa (there are identification difficulties) rather than structure and functions; correlation rather than causation; application within a limited biogeographical area; reliance on ‘expert’ judgement; high precision but poor accuracy; poorly defined reference conditions; lack of independent tests; and an inability to discriminate reliably between the target pressures of interest from confounding background variables.

4. IBMR was a far better indicator of pH (or HCO3‐pCO2) than it was of soluble reactive phosphorus, SRP (or SRP‐NH4). While there was a highly significant correlation between IBMR and SRP after removing the effect of pH, the relationship was weak (r2 = 0.08, n = 215, P < 0.001).

5. LEAFPACS is a multi‐metric method summing up five individual indices, each compliant with the WFD. Its individual metrics were not better correlated with nutrient and hydromorphological pressures (with r2 < 0.1, n = 62, P < 0.05) than was the IBMR. The meaning of the overall metric is questionable.

6. There are problems in determining the precision of the indices, owing to uncertainties in recording, but they are less than the uncertainties in determining accuracy (because species optima and tolerances are sometimes poorly known).

7. Reliable information is needed to improve the state of our rivers. Macrophyte indices are able to detect statistically significant pressures from a large population of sites but cannot be applied at specific sites, as required by the WFD, owing to large uncertainties and low explanatory power. Typically, more than 90% of the variability in macrophyte indices is attributed to factors other than human pressure. The WFD would be better served by a simpler, holistic approach based on our current mechanistic understanding of river processes. These findings are likely to apply also to other taxonomic groups (macroinvertebrates, diatoms, fish) used in the assessment of purported ecological quality and to palaeolimnological measures of reference status.
The role of male chromosomal polymorphism played in spermatogenesis and the outcome of IVF/ICSI‐ET treatment
Authors: Guo T. , Qin Y. , Gao X. , Chen H. , Li G. , Ma J. , Chen Z.‐J.
Published: June 2012

Chromosomal polymorphism has been reported to be associated with infertility, but its effect on IVF/ICSI‐ET outcome is still controversial. To evaluate whether or not chromosomal polymorphism in men plays a role in spermatogenesis and the outcome of IVF/ICSI‐ET, we retrospectively analysed 281 infertile couples. Measures included fertilization rate, implantation rate, pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate, early miscarriage rate and preterm rate. Men with chromosomal polymorphism had significantly higher frequencies of severe oligozoospermia and azoospermia than those without (37.12% vs. 16.11%, p < 0.001; 27.27% vs. 10.74%, p < 0.001; respectively). Significantly, lower fertilization rate (68.02% vs. 78.00%, p < 0.001) and clinical pregnancy rate (45.00% vs. 66.67%, p = 0.031) were observed in polymorphism‐carrying men with severe oligozoospermia compared with non‐carriers with severe oligozoospermia. This suggests that chromosomal polymorphism has adverse effects on spermatogenesis, negatively influencing the outcome of IVF/ICSI‐ET treatment. Polymorphic variations on the Y chromosome have been found to be the most prevalent polymorphism in infertile men, most frequently occurring in patients with severe oligozoospermia.
What are the core elements of patient‐centred care? A narrative review and synthesis of the literature from health policy, medicine and nursing
Authors: Kitson Alison , Marshall Amy , Bassett Katherine , Zeitz Kathryn
Published: June 2012

Aim.  To identify the common, core elements of patient‐centred care in the health policy, medical and nursing literature.

Background.  Healthcare reform is being driven by the rhetoric around patient‐centred care yet no common definition exists and few integrated reviews undertaken.

Design.  Narrative review and synthesis.

Data sources.  Key seminal texts and papers from patient organizations, policy documents, and medical and nursing studies which looked at patient‐centred care in the acute care setting. Search sources included Medline, CINHAL, SCOPUS, and primary policy documents and texts covering the period from 1990–March 2010.

Review methods.  A narrative review and synthesis was undertaken including empirical, descriptive, and discursive papers. Initially, generic search terms were used to capture relevant literature; the selection process was narrowed to seminal texts (Stage 1 of the review) and papers from three key areas (in Stage 2).

Results.  In total, 60 papers were included in the review and synthesis. Seven were from health policy, 22 from medicine, and 31 from nursing literature. Few common definitions were found across the literature. Three core themes, however, were identified: patient participation and involvement, the relationship between the patient and the healthcare professional, and the context where care is delivered.

Conclusion.  Three core themes describing patient‐centred care have emerged from the health policy, medical, and nursing literature. This may indicate a common conceptual source. Different professional groups tend to focus on or emphasize different elements within the themes. This may affect the success of implementing patient‐centred care in practice.
A physiologically based pharmacokinetics model for florfenicol in crucian carp and oral‐to‐intramuscular extrapolation
Authors: YANG F. , SUN N. , SUN Y. X. , SHAN Q. , ZHAO H. Y. , ZENG D. P. , ZENG Z. L.
Published: June 2012

Yang, F., Sun, N., Sun, Y. X., Shan, Q., Zhao, H. Y., Zeng, D. P., Zeng, Z. L. A physiologically based pharmacokinetics model for florfenicol in crucian carp and oral‐to‐intramuscular extrapolation. J. vet. Pharmacol. Therap. 36, 192–200.

In this study, an oral physiologically based pharmacokinetics (PBPK) model was developed for florfenicol in crucian carp (Carassius auratus). Subsequently, oral‐to‐intramuscular extrapolation was performed and the two models were used to predict florfenicol concentrations in the edible tissues of crucian carp. The oral model gave good predictions in most tissues, except for kidney and liver in which the florfenicol concentrations were underestimated at the later time points. In contrast, using the intramuscular model, the concentrations in the kidney were overestimated at the later time points. Both models had the best predictive ability in the main edible tissue, the muscle. The oral model also accurately predicted the florfenicol concentrations in the muscle after multiple doses. The present study demonstrated the feasibility of predicting florfenicol concentrations in the edible tissues of crucian carp using a route‐to‐route extrapolation method.
Rapid high‐amplitude circumferential slow wave propagation during normal gastric pacemaking and dysrhythmias
Authors: O’Grady G. , Du P. , Paskaranandavadivel N. , Angeli T. R. , Lammers W. J. E. P. , Asirvatham S. J. , Windsor J. A. , Farrugia G. , Pullan A. J. , Cheng L. K.
Published: June 2012

Background  Gastric slow waves propagate aborally as rings of excitation. Circumferential propagation does not normally occur, except at the pacemaker region. We hypothesized that (i) the unexplained high‐velocity, high‐amplitude activity associated with the pacemaker region is a consequence of circumferential propagation; (ii) rapid, high‐amplitude circumferential propagation emerges during gastric dysrhythmias; (iii) the driving network conductance might switch between interstitial cells of Cajal myenteric plexus (ICC‐MP) and circular interstitial cells of Cajal intramuscular (ICC‐IM) during circumferential propagation; and (iv) extracellular amplitudes and velocities are correlated.

Methods  An experimental–theoretical study was performed. High‐resolution gastric mapping was performed in pigs during normal activation, pacing, and dysrhythmia. Activation profiles, velocities, and amplitudes were quantified. ICC pathways were theoretically evaluated in a bidomain model. Extracellular potentials were modeled as a function of membrane potentials.

Key Results  High‐velocity, high‐amplitude activation was only recorded in the pacemaker region when circumferential conduction occurred. Circumferential propagation accompanied dysrhythmia in 8/8 experiments was faster than longitudinal propagation (8.9 vs 6.9 mm s−1; P = 0.004) and of higher amplitude (739 vs 528 μV; P = 0.007). Simulations predicted that ICC‐MP could be the driving network during longitudinal propagation, whereas during ectopic pacemaking, ICC‐IM could outpace and activate ICC‐MP in the circumferential axis. Experimental and modeling data demonstrated a linear relationship between velocities and amplitudes (P < 0.001).

Conclusions & Inferences  The high‐velocity and high‐amplitude profile of the normal pacemaker region is due to localized circumferential propagation. Rapid circumferential propagation also emerges during a range of gastric dysrhythmias, elevating extracellular amplitudes and organizing transverse wavefronts. One possible explanation for these findings is bidirectional coupling between ICC‐MP and circular ICC‐IM networks.
Decision influences and aftermath: parents, stillbirth and autopsy
Authors: Horey Dell , Flenady Vicki , Conway Liz , McLeod Emma , Yee Khong Teck
Published: June 2012

Background  Stillbirth, among the most distressing experiences an adult may face, is also a time when parents must decide whether an autopsy or other post‐mortem examinations will be performed on their infant. Autopsies can reveal information that might help explain stillbirth, yet little is known about how people make this difficult decision.

Objectives  This study examines the influences on decisions about autopsy after stillbirth among Australian parents.

Design  The study involved secondary analysis of transcripts of three focus groups using qualitative content analysis.

Participants and setting  Seventeen parents of 14 stillborn babies participated in consultations around the revision of a perinatal mortality audit guideline.

Results  Parents shared the decision making. Four decision drivers were identified: parents’ preparedness or readiness to make decisions; parental responsibility; concern for possible consequences of an autopsy and the role of health professionals. Each decision driver involved reasons both for and against autopsy. Two decision aftermath were also present: some parents who agreed to an autopsy were dissatisfied with the way the autopsy results were given to them and some parents who did not have an autopsy for their infant expressed some form of regret or uncertainty about the choice they made.

Conclusions  To make decisions about autopsy after stillbirth, parents need factual information about autopsy procedures, recognition that there might be fear of blame, an environment of trust, and health services and professionals prepared and skilled for difficult conversations.
Canker and dieback on Platanus x acerifolia caused by Diaporthe scabra
Authors: Grasso F. M. , Marini M. , Vitale A. , Firrao G. , Granata G.
Published: June 2012

Cankers and dieback on London plane caused by Diaporthe scabra have been observed in urban plantings in Catania, Italy. Symptoms were delayed spring flush, trunk cankers, small chlorotic leaves associated with dead terminal or lateral branches and an early defoliation. Isolations from infected wood on PDA led to the isolation of the anamorph Phomopsis scabra with α‐conidia production. The infected wood placed in a moist chamber developed pycnidia with α and β conidia and perithecia of the teleomorph D. scabra. Sequence analysis of the internal transcribed spacers ITS1 and ITS2, the ribosomal intragenic spacer beta‐tubulin 1 and beta‐tubulin 2 genes, congruently indicated that the D. scabra isolate is phylogenetically related to two strains of D. helianthi isolated in Italy from sunflower and to strains of D. eres. Inoculations on young plants of London plane growing in pots confirmed the pathogenicity of the isolated fungus. To our knowledge, this is the first report of the disease in Italy.
Root and butt rot caused by Heterobasidion annosum in Atlantic coniferous ecosystems of Spain
Authors: Mesanza N. , Iturritxa E.
Published: June 2012

In the second half of the 20th century, the forested surface in northern Spain started to increase during a process of reforestation and the replacement of native forest. This reforestation was performed mostly by introducing monocultures of exotic coniferous species. One of the implications of intense forest exploitation and the introduction of new forest species is an increase in disease outbreaks. Because the genus Heterobasidion includes some of the most significant conifer pathogens in the world, surveys were conducted to collect and identify
H

eterobasidion isolates associated with diverse hosts within coniferous forests and plantations in the Basque Country, northern Spain. A total of 159 stands were surveyed, and 45 isolates were obtained from different trees. Based on sequencing of the internal transcribed spacer region of the ribosomal DNA, all collected isolates were identified as European
H

eterobasidion annosum s.s. (European P‐type). Heterobasidion annosum was detected in 28.3% of the sampled stands, with the following distribution by host: Chamaecyparis lawsoniana (11.1%),
P

inus pinaster (2.2%),
P

. radiata (42.2%),
P

. nigra (2.2%),
P

. sylvestris (17.8%),
P

seudotsuga menziesii (17.8%) and
P

icea abies (6.7%). The spatial distribution of the population showed a high degree of clustering. This is the first report of
H
. annosum s.s. causing damage to forest plantations of Chamaecyparis lawsoniana,
P

inus pinaster,
P

. radiata,
P

seudotsuga menziesii and
P

icea abies in Spain. In the current context of forest pathosystems, the management practice of replacing susceptible forest species with resistant species is recommended.
Interventional pulmonology: Focus on pulmonary diagnostics
Authors: CZARNECKA KASIA , YASUFUKU KAZUHIRO
Published: June 2012

Interventional pulmonology (IP) allows comprehensive assessment of patients with benign and malignant airway, lung parenchymal and pleural disease. This relatively new branch of pulmonary medicine utilizes advanced diagnostic and therapeutic techniques to treat patients with pulmonary diseases. Endobronchial ultrasound revolutionized assessment of pulmonary nodules, mediastinal lymphadenopathy and lung cancer staging allowing minimally invasive, highly accurate assessment of lung parenchymal and mediastinal disease, with both macro‐ and microscopic tissue characterization including molecular signature analysis. High‐spatial resolution, new endobronchial imaging techniques including autofluorescence bronchoscopy, narrow‐band imaging, optical coherence tomography and confocal microscopy enable detailed evaluation of airways with increasing role in detection and treatment of malignancies arising in central airways. Precision in peripheral lesion localization has been increased through innovative navigational techniques including navigational bronchoscopy and electromagnetic navigation. Pleural diseases can be assessed with the use of non‐invasive pleural ultrasonography, with high sensitivity and specificity for malignant disease detection. Medical pleuroscopy is a minimally invasive technique improving diagnostic safety and precision of pleural disease and pleural effusion assessment. In this review, we discuss the newest advances in diagnostic modalities utilized in IP, indications for their use, their diagnostic accuracy, efficacy, safety and challenges in application of these technologies in assessment of thoracic diseases.
Ocular toxoplasmosis II: clinical features, pathology and management
Authors: Butler Nicholas J , Furtado João M , Winthrop Kevin L , Smith Justine R
Published: June 2012

Abstract

The term, ocular toxoplasmosis, refers to eye disease related to infection with the parasite, Toxoplasma gondii. Recurrent posterior uveitis is the typical form of this disease, characterized by unilateral, necrotizing retinitis with secondary choroiditis, occurring adjacent to a pigmented retinochoroidal scar and associated with retinal vasculitis and vitritis. Multiple atypical presentations are also described, and severe inflammation is observed in immunocompromised patients. Histopathological correlations demonstrate focal coagulative retinal necrosis, and early in the course of the disease, this inflammation is based in the inner retina. For typical ocular toxoplasmosis, a diagnosis is easily made on clinical examination. In atypical cases, ocular fluid testing to detect parasite DNA by polymerase chain reaction or to determine intraocular production of specific antibody may be extremely helpful for establishing aetiology. Given the high seroprevalence of toxoplasmosis in most communities, serological testing for T. gondii antibodies is generally not useful. Despite a lack of published evidence for effectiveness of current therapies, most ophthalmologists elect to treat patients with ocular toxoplasmosis that reduces or threatens to impact vision. Classic therapy consists of oral pyrimethamine and sulfadiazine, plus systemic corticosteroid. Substantial toxicity of this drug combination has spurred interest in alternative antimicrobials, as well as local forms of drug delivery. At this time, however, no therapeutic approach is curative of ocular toxoplasmosis.
Does amblyopia have a functional impact? Findings from the Dunedin Multidisciplinary Health and Development Study
Authors: Wilson Graham A , Welch David
Published: June 2012

Abstract

Background:  Existing data on the functional impact of amblyopia are conflicting. The functional impact of amblyopia is a critical component of the viability and effectiveness of childhood vision screening programmes and treatment regimes.

Design:  Prospective longitudinal birth cohort (the Dunedin Multidisciplinary Health and Development Study).

Participants:  One thousand thirty‐seven children born in Dunedin, New Zealand, between April 1972 and March 1973, assessed from ages 3 to 32 years.

Methods:  Comparison of study members with no amblyopia, recovered amblyopia, possible amblyopia or amblyopia according to both classic (6/12 visual acuity or worse in at least one eye, or a two‐line or greater differential between the visual acuity in both eyes) and modern (6/9 visual acuity or worse in at least one eye) definitions of amblyopia.

Main Outcome Measures:  Childhood motor development, teenage self‐esteem and adult socioeconomic status (assessed by occupation, education, reading ability and income).

Results:  There was no evidence of poorer motor development, lower self‐esteem or reduced adult socioeconomic status in study members with amblyopia or recovered amblyopia when compared with those with no amblyopia.

Conclusions:  Amblyopia or having recovered amblyopia does not functionally impact on childhood motor development, teenage self‐esteem or adult socioeconomic status within this cohort. The wide range of visual deficits and adaptations that are known to occur in amblyopic vision do not translate into important ‘real life’ outcomes for the study members with amblyopia or recovered amblyopia. The age‐related cumulative lifetime risk of bilateral visual impairment in amblyopia will be assessed in future studies.
An integrated approach to design novel therapeutic interventions for demyelinating disorders
Authors: Vidaurre Oscar G. , Liu Jia , Haines Jeffery , Sandoval Juan , Nowakowski Richard , Casaccia Patrizia
Published: June 2012

Therapeutic strategies are often based on two general principles: interference with the pathogenic process and repair of the damaged tissues. Recent studies, however, have suggested that several pathological conditions may result from the interplay between genetic susceptibility traits and environmental influences that, by modulating the epigenome, also affect disease onset and progression. Based on lessons from neural development, it is conceivable that new lines of preventive and possibly therapeutic intervention might be developed to modulate disease onset or decrease the severity of the symptoms. This review will discuss these concepts within the context of multiple sclerosis, the most common demyelinating disease of the central nervous system, and the leading cause of progressive neurological disability in young adults.
What does the developing brain tell us about neural diseases?
Authors: Stoeckli Esther T.
Published: June 2012

In a recently published report, the European Brain Council estimated that the annual cost of brain disorders is larger than the cost of all other disease areas combined, including cardiovascular diseases, cancer, and diabetes. The World Health Organization concluded that approximately one‐third of the total burden of disease in Europe is attributable to brain disorders. Therefore, drug development for neural diseases should flourish and attract large pharmaceutical companies and smaller enterprises alike. However, this is far from being the case: industry is cutting down on research and investment in brain disorders in Europe. Political reasons may be contributing to this, but they do not constitute the only explanation. An important reason for the decreasing interest and investment is the lack of drug targets in neural diseases. In order to change this, greater efforts at understanding the etiologies and pathogenetic mechanisms of disorders of both the developing and the adult brain are required. We need to strengthen basic research to understand the brain in health and disease. A shift from translational to basic research is required to meet the need for drugs and therapies in the future. In support of this, I summarize some recent studies indicating that the developing brain has much to offer in this respect. The processes and genes involved in brain development are linked to the etiologies not only of neurodevelopmental but also of neurodegenerative diseases.
The IMF, the World Bank, and the Global Economic Crisis: Exploring Paradigm Continuity
Authors: Güven Ali Burak
Published: June 2012

A thematic examination of the IMF and the World Bank's recent crisis programmes finds strong evidence of prescriptive continuity with the pre‐crisis repertoire of these organizations, contradicting their legacy of policy adaptation during times of systemic turbulence. How are we to account for this anomaly? The current specialist literature on the Fund and Bank offers plausible explanations, mainly by stressing principal–agent relations and intra‐organizational dynamics. Yet these lender‐oriented approaches need to be complemented by looking at the demand side of the lending relationship as well, that is, by focusing on the Fund and Bank's borrowers. Of particular relevance is the growing diversification of development trajectories in the South, which creates strong disincentives against paradigm recalibration. The article highlights the analytic potential of one vital dimension of this diversification: the shrinking common ground of macroeconomic failure in large emerging economies, illustrated here in a brief comparison of Mexico, Thailand and Turkey.
Between Hermeneutics and Formalism: the Lento from Tippett's Concerto for Orchestra (Or: Music Analysis after Lawrence Kramer)
Authors: CLARKE DAVID
Published: June 2012

An account of the slow movement of Tippett's Concerto for Orchestra can be productively interwoven with a discussion about musical meaning. This provides a focus for the question of whether musical meaning should be regarded as primarily intrinsic or as located within what is linguistically predicable of music within cultural (or ‘worldly’) discourses. Methodologically, this is homologous with a distinction between formalist and hermeneutic approaches, corresponding loosely to disciplinary distinctions between music analysis and approaches of the so‐called New Musicology. The work of Lawrence Kramer is paradigmatic of the latter, while writings by Derek Puffett, notably his analysis of Tippett's Second Quartet, illustrate the former.

Complementary analyses of the Lento from Tippett's Concerto, drawing on the composer's second opera, King Priam, as an intertext, reveal the potential and limitations of hermeneutics and formalism. I suggest that we should not be misguided into an a priori privileging of one approach over the other, but instead attempt correctly to construe the relationship between them. Kramer considers analysis to be no more (or less) than the means to hermeneutics, and assumes the possibility of a relatively unproblematic translation from one mode of enquiry to the other. But the knowledge they produce is not coterminous, which leaves open the pursuit of the musically intrinsic, as well as the question of what approaches are suggested by the space between.
Development, cognition, and behaviour in Pitt–Hopkins syndrome
Authors: VAN BALKOM INGRID D C , VUIJK PIETER JELLE , FRANSSENS MARIJKE , HOEK HANS W , HENNEKAM RAOUL C M
Published: June 2012

Aim  The aim of the study was to collect detailed data on behavioural, adaptive, and psychological functioning in 10 individuals with Pitt–Hopkins syndrome (PTHS), with specific attention to manifestations of autism spectrum disorder (ASD).

Method  The participants (four females, six males), residing in the Netherlands and Belgium, were ascertained through the Dutch national PTHS support group. Median age of participants was 10 years, the age range was between 32 and 289 months. They underwent psychiatric examinations and neuropsychological measurements using a comprehensive assessment battery. Additionally, parental information was gathered through standardized interviews and questionnaires. Findings were compared with those from the literature.

Results  All participants showed profound intellectual disability, amiable demeanour with minimal maladaptive behaviours, severe impairments of communication and language, and intense, frequent motor stereotypies. Impairments in all participants were beyond what would be expected for cognitive abilities, fitting a classification of ASD.

Interpretation  Patients with PTHS are characterized not only by specific physical and genetic manifestations but also by specific behavioural and cognitive characteristics. Studying behaviour and cognition may improve diagnosis and prognosis, allows recognition of comorbidities, and contributes to adequate counselling of families.
Dysautonomia after pediatric brain injury
Authors: BAGULEY IAN J
Published: June 2012

This commentary is on the original article by Kirk et al. on pages 759‐764 of this issue
Stigma in school‐based mental health: perceptions of young people and service providers
Authors: Bowers Hayley , Manion Ian , Papadopoulos Despina , Gauvreau Emily
Published: June 2012

Background

Mental health affects one in five young people, with the majority avoiding help due to stigma. In this study, young people's (n = 49) perception of stigma as a barrier to accessing school‐based mental health services was compared with that of service providers (n = 63), along with the perceived extent of mental health problems and availability of school‐based mental health resources.

Method

Participants completed a survey or interview. EBSCO and PubMed databases were used for the duration of this study, from August 2010 to September 2011.

Results

A greater proportion of young people versus providers reported stigma as the largest barrier to accessing mental health services. In addition, most young people reported that school‐based mental health resources were scarce.

Conclusions

These results emphasize the need for young people's involvement in mental health initiatives.
Redescription and palaeobiology ofPalaeoscorpius devonicusLehmann, 1944 from the Lower Devonian Hunsrück Slate of Germany
Authors: KÜHL GABRIELE , BERGMANN ALEXANDRA , DUNLOP JASON , GARWOOD RUSSEL J. , RUST JES
Published: June 2012

Abstract: Palaeoscorpius devonicusLehmann, 1944 is known from only a single specimen, found in the Eschenbach Pit near Bundenbach in the Lower Devonian Hunsrück Slate of Germany. It is a key fossil, having been interpreted both as the most basal member of the Scorpiones and as one of the order’s most likely candidates for an aquatic mode of life. Prepared both ventrally and dorsally, some aspects of its morphology remain problematic. Here, with the aid of new techniques, including computed tomography, we present a re‐investigation of this scorpion’s anatomy and a new reconstruction, with a particular focus on the species’ original habitat. On the basis of the environmental interpretation of the Hunsrück Slate and the completeness of the specimen, previous authors concluded thatP. devonicuswas marine, but none offered convincing morphological evidence. Recent studies of the deposit’s environment suggest that the Hunsrück Sea was part of an intrashelf basin, relatively close to the coastline, and fossils of land plants show that terrestrial wash‐in occasionally occurred. Our revised interpretation of the fossil’s morphology demonstrates that the scorpion was most probably terrestrial. Internal mesosomal organs are interpreted as book lungs, but other terrestrial adaptations are lacking. The absence of both coxapophyses and gnathobases makes determining the scorpion’s feeding mechanism difficult. Interpreting the scorpion’s character states within a phylogenetic framework, especially the possible presence of book lungs, implies either that the plesiomorphic position ofP. devonicusis no longer supported or that the development of book lungs had already taken place early in the scorpion lineage.
Portal hypertension and liver cirrhosis in rats: effect of the β3‐adrenoceptor agonist SR58611A
Authors: Vasina Valentina , Giannone Ferdinando , Domenicali Marco , Latorre Rocco , Berzigotti Annalisa , Caraceni Paolo , Zoli Marco , De Ponti Fabrizio , Bernardi Mauro
Published: June 2012

BACKGROUND AND PURPOSE β3‐Adrenoceptors participate in the regulation of vascular tone in physiological and pathological conditions. We aimed to assess the effect of pharmacological modulation of β3‐adrenoceptors on portal pressure (PP) and systemic haemodynamics and their expression in the liver and mesenteric vessels of cirrhotic rats.

EXPERIMENTAL APPROACH PP, central venous pressure (CVP) and systemic haemodynamics were invasively assessed in control and CCl4‐treated cirrhotic rats before and during infusion of the selective β3‐adrenoceptor agonist, SR58611A. Tissue samples were also collected from liver, heart, portal vein and mesenteric artery for immunohistochemistry and molecular biology analysis. The effect of SR58611A on isolated portal vein was assessed.

KEY RESULTS At baseline, cirrhotic rats showed portal hypertension, reduced CVP and hyperdynamic circulation. SR58611A induced a significant, dose‐dependent decrease in PP in cirrhotic rats, but not in controls. Although both groups manifested a dose‐dependent reduction in mean arterial pressure, this effect was associated with decreased cardiac index (CI) and unchanged indicized peripheral vascular resistance (PVRI) in cirrhotic rats and increased CI and decreased PVRI in control animals. Pretreatment with the selective β3‐adrenoceptor antagonist SR59230 prevented all SR58611A‐induced changes in cirrhotic rats. SR58611A concentration‐dependently relaxed portal vein in cirrhotic rats to a significantly greater extent than in healthy rats; pretreatment with SR59230A completely prevented SR58611A‐induced cirrhotic portal vein relaxation. Finally, β3‐adrenoceptors were identified in the liver, heart and portal vein of cirrhotic and control animals; their expression was increased in cirrhotic rats.

CONCLUSIONS AND IMPLICATIONS β3‐Adrenoceptors are altered in portal hypertension of experimental cirrhosis and may represent a novel therapeutic target.
An ultrathin poly(l‐lactic acid) nanosheet as a burn wound dressing for protection against bacterial infection
Authors: Miyazaki Hiromi , Kinoshita Manabu , Saito Akihiro , Fujie Toshinori , Kabata Koki , Hara Etsuko , Ono Satoshi , Takeoka Shinji , Saitoh Daizoh
Published: June 2012

Burn wounds are highly susceptible to bacterial infection due to impairment of the skin's integrity. Therefore, prevention of bacterial colonization/infection in the wound is crucial for the management of burns, including partial‐thickness burn injuries. Although partial‐thickness burn injuries still retain the potential for reepithelialization, the complication of wound infection severely impairs the reepithelialization even in such superficial burn injuries. We recently developed a biocompatible nanosheet consisting of poly(l‐lactic acid) (PLLA). The PLLA nanosheets have many useful and advantageous biological properties for their application as a wound dressing, such as sufficient flexibility, transparency, and adhesiveness. We herein investigated the suitability of the PLLA nanosheets as a wound dressing for partial‐thickness burn wounds in mice. The PLLA nanosheets tightly adhered to the wound without any adhesive agents. Although wound infection with Pseudomonas aeruginosa in the controls significantly impaired reepithelialization of burn wounds, dressing with the PLLA nanosheet markedly protected against bacterial wound infection, thereby improving wound healing in the mice receiving partial‐thickness burn injuries. The PLLA nanosheet also showed a potent barrier ability for protecting against bacterial penetration in vitro. The ultrathin PLLA nanosheet may be applied as a protective dressing to reduce environmental contamination of bacteria in a partial‐thickness burn wound.
Interferon‐gamma inhibits healing post scald burn injury
Authors: Shen Haitao , Yao Pamela , Lee Eunyoung , Greenhalgh David , Soulika Athena M.
Published: June 2012

Impaired healing after severe burns remains a reason for prolonged hospitalization, opportunistic infections, and debilitating scarring. Interferon‐gamma (IFN‐γ) is an important immune regulator that has been shown to inhibit collagen synthesis by fibroblasts, resulting in delayed healing in incision wounds. To determine whether IFN‐γ plays similar roles in the healing process after severe burn, we induced scald injury in mice deficient or sufficient in IFN‐γ and examined local responses. In the absence of IFN‐γ, scalded areas healed faster. This was associated with attenuated local inflammatory responses, enhanced reepithelialization, increased proliferation of keratinocytes in reepithelialized leading edges, and up‐regulation of growth factors in burned skin areas. Furthermore, angiogenesis and myofibroblast formation commenced and terminated earlier in IFN‐γ–/– mice compared with wild type (WT) controls. Our observations demonstrate that inhibition of IFN‐γ results in accelerated healing after burn injury by dampening excessive inflammation and facilitating reepithelialization, collagen deposition, and wound contraction.
Reduction of burn progression with topical delivery of (antitumor necrosis factor‐α)‐hyaluronic acid conjugates
Authors: Sun Liang Tso , Friedrich Emily , Heuslein Joshua L. , Pferdehirt Rachel E. , Dangelo Nicole M. , Natesan Shanmugasundaram , Christy Robert J. , Washburn Newell R.
Published: June 2012

In this study, we explored whether topical application of antibodies targeting tumor necrosis factor‐α (TNF‐α) or interleukin‐6 (IL‐6) conjugated to hyaluronic acid (HA) could reduce the extension of necrosis by modulating inflammation locally in a partial‐thickness rat burn model. Partial‐thickness to deep partial‐thickness burn injuries present significant challenges in healing, as these burns often progress following the initial thermal insult, resulting in necrotic expansion and increased likelihood of secondary complications. Necrotic expansion is driven by a microenvironment with elevated levels of pro‐inflammatory mediators, and local neutralization of these using antibody conjugates could reduce burn progression. Trichrome‐stained tissue sections indicated the least necrotic tissue in (anti‐TNF‐α)‐HA‐treated sites, while (anti‐IL‐6)‐HA‐treated sites displayed similar outcomes to saline controls. This was confirmed by vimentin immunostaining, which demonstrated that HA treatment alone reduced burn progression by nearly 30%, but (anti‐TNF‐α)‐HA reduced it by approximately 70%. At all time points, (anti‐TNF‐α)‐HA‐treated sites showed reduced tissue levels of IL‐1β compared to controls, suggesting inhibition of a downstream mediator of inflammation. Decreased macrophage infiltration in (anti‐TNF‐α)‐HA‐treated sites compared to controls was elucidated by immunohistochemical staining of macrophages, suggesting a reduction in overall inflammation in all time points. These results suggest that local targeting of TNF‐α may be an effective strategy for preventing progression of partial‐thickness burns.
Declining egg viability explains higher hatching failure in a suburban population of the threatened Florida scrub‐jay Aphelocoma coerulescens
Authors: Aldredge Robert A. , LeClair Sonya C. , Bowman Reed
Published: June 2012

Hatching failure occurs in approximately 10% of all avian eggs, but varies both within and among species. This reduction in viable offspring can have significant fitness consequences for breeding parents; therefore, it is important to understand which factors influence variation in hatching failure among populations. Previous research suggests that hatching failure is higher in a suburban than in a wildland population in the Florida scrub‐jay. From 2003 to 2007, we performed two experiments to examine whether increased hatching failure in the suburbs resulted from 1) increased length of off‐bouts during incubation (predation risk hypothesis, 2003–2004) or 2) increased exposure to ambient temperature during laying (egg viability hypothesis, 2005–2007). Hatching failure was higher for females that took fewer off‐bouts, but the length of those off‐bouts did not influence hatching failure. Thus, nest predation risk does not appear to explain higher hatching failure in the suburbs. Alternatively, hatching failure increased with increasing exposure of eggs to ambient conditions during the laying period. First‐laid eggs in the suburbs had the greatest pre‐incubation exposure to ambient temperature and the greatest rate of hatching failure, consistent with the egg viability hypothesis. Urbanization influences hatching failure through a series of complex interactions. Access to predictable food sources advances mean laying date in suburban scrub‐jays, leading to larger clutch sizes. Because scrub‐jays begin incubation with the ultimate egg, first‐laid eggs in the suburbs may be exposed to ambient temperatures for longer periods, thus reducing their viability.