bluuebunny/crossref_metadata_2025 huggingface dataset:
Speech perception in congenitally, pre‐lingually and post‐lingually deaf children expressed in an equivalent hearing loss value
Authors: Rotteveel L.J.C. , Snik A.F.M. , Vermeulen A.M. , Cremers C.W.R.J. , Mylanus E.A.M.
Published: December 2008

Objectives:  To investigate the speech perception performance of children with a cochlear implant (CI) after 3 and 4 years of follow‐up and to study the influence of age at implantation, duration of deafness and communication mode on the variability in speech perception performance.

Study design:  A broad battery of speech perception tests was administered to 67 children with a CI. The results were reduced into one measure: the ‘equivalent hearing loss (EHL)’. This outcome measure refers to the performance of a reference group of severely and profoundly hearing impaired children with conventional hearing aids.

Participants:  The population comprised 35 congenitally, 17 pre‐lingually and 15 post‐lingually deaf children implanted between 1989 and 1999. The population was homogeneous with respect to cognition, residual hearing and support at home as a result of conservative inclusion criteria.

Results:  During the first 2 years after implantation, post‐lingually deaf children showed the fastest rate of improvement in speech perception. After 3 years of implant use, the early implanted pre‐lingually deaf children and congenitally deaf children implanted under the age of 6 years caught up with the post‐lingually deaf children. Pre‐lingually deaf children implanted after a relatively long‐duration of deafness tended to show poorer performance than those with a shorter duration. Performance of congenitally deaf children implanted after the age of 6 years was poorer and progress was slower. In the congenitally deaf children, 36% of the variability in performance was explained by duration of deafness, whereas in the children with pre‐ and post‐lingually acquired deafness, communication mode explained 69% of the variance.

Conclusions:  All children derived benefit from their CI for speech perception tasks, but performance varied greatly. Several children reached EHL levels around 70 dB; their speech perception was equal to that of a child with conventional hearing aids who has 70 dB HL. After early implantation, the levels of performance that were eventually achieved differed no more than 10 dB, irrespective of whether the onset of deafness was pre‐lingual or postlingual. In congenitally deaf children, duration of deafness played a major role in speech perception performance, whereas in the children with pre‐lingually and post‐lingually acquired deafness together, mode of communication was a major factor.
The inflammation produced by corticosteroid inhalers in the pharynx in asthmatics
Authors: Bhalla R.K. , Taylor W. , Jones A.S. , Roland N.J.
Published: December 2008

Objectives:  To investigate inflammation of the pharyngeal mucosa caused by inhaled corticosteroids.

Design:  Prospective, cross‐sectional, single‐blinded study.

Setting:  University Hospital Aintree, Liverpool, UK.

Patients:  Fifty adults were recruited from two local general practices and from general ENT clinics at our University hospital. Patients were allocated to one of four groups according to use of inhaled corticosteroids and the presence of adverse local side effects.

Main outcome measures:  Scores achieved on a respiratory symptom questionnaire. Histological markers of inflammation and their correlation with pharyngitis. Statistical modelling included univariate and multivariate analyses, which included multiple linear and logistic regression, and discriminant analysis.

Results:  The regular use of inhaled corticosteroids predisposed subjects to hoarseness, weakness of voice, sore throat and throat irritation (P < 0.0001). Pharyngitis was significantly different between the groups (P < 0.0001). Furthermore, those not using an inhaled corticosteroid regularly had little or no clinically apparent pharyngitis, whereas those using an inhaled corticosteroid regularly had significantly higher pharyngitis scores (P = 0.0204). Similarly, weakness of voice (P = 0.0234), hoarseness (P < 0.001) and sore throat (P < 0.001) were also more common in those patients that used an inhaled corticosteroid on a regular basis. To our surprise, however, cellular markers of inflammation did not corroborate the appearances of clinical examination. We found that the five most important discriminators, between those that were using inhaled corticosteroid therapy regularly and those that were not, to be intra‐epithelial inflammatory cells (scdf −1.2939); age (scdf 0.8389); use of a spacer device (scdf 0.5456); sore throat (scdf 0.4230) and throat irritation (scdf 0.4015). The groups were significantly different (P < 0.0001). The statistical model used, classified 68% of the cases correctly into their respective groups.

Conclusions:  Inhaled corticosteroids predispose to pharyngitis and an inflammatory infiltrate. However, the clinical diagnosis of pharyngitis does not correlate well with cellular inflammatory infiltrate and is therefore, not a reliable measure of underlying inflammation. We advocate caution in the use of pharyngeal erythema as a measure of underlying inflammation.
Transimmunization for immunotherapy of head and neck squamous cell carcinoma (HNSCC)
Authors: Prasad S. , Cody V. , Hanlon D. , Roberts S. , Filler R. , Edelson R.L. , Dobrucki W. , Sinusas A. , Girardi M. , Birchall M.A.
Published: December 2008

Objective.  To establish proof of principle of transimmunization (T.I.) in an animal model prior to use in a dendritic cell (DC)‐based immunotherapy clinical trial for HNSCC.

Methods.  Pooled blood from syngeneic Fischer 344 rats was photoactivated in the presence of 8‐methoxypsoralen and Ultraviolet‐A, followed by overnight incubation to facilitate conversion of monocyte precursors to DC. Cells were matured using pathogen associated molecular patterns (PAMPs) – LPS, CpG DNA, flagellin and Poly I: C. Cells were either labeled with Indium‐111 and injected peritumorally followed by in vivo tracking using micro‐Single Photon Emission CT (micro‐SPECT), or used unlabeled in randomized double‐blinded vaccination studies in tumor‐bearing animals. Treatment groups included: T.I. cells ± PAMPs, T.I. cells + lysate ± PAMPs and T.I. cells + tumor lysate (TL) containing‐NP ± PAMPs. Outcome measures included: mean tumor size, survival and ELISA to study differences in production of IFN‐γ and IL‐10.

Results.  There were statistically significant differences in mean tumor size at 2 weeks post‐injections (P = 0.033) and overall survival (P = 0.009) in the group treated with T.I. cells alone. Addition of PAMPs made no significant impact on outcome measures. Micro‐SPECT images indicated that T.I. cells remain at the site of injection between 24 and 96 h.

Conclusions.  (1) Immature T.I. cells on their own appear to be significantly more effective than those loaded with antigen, or mature ones. (2) T.I. cells remain at the site of injection for at least 24 h prior to migration to regional lymph nodal area for classical antigen cross‐presentation.
A systematic review of the role of mutant p53 in predicting outcome or response to treatment in head and neck squamous cell carcinoma (HNSCC).
Authors: Tandon S. , Tudur‐Smith C. , Ghosh S. , Boyd M. , Jones T.M.
Published: December 2008

Objectives.  To systematically review whether the presence of mutant p53 alters patients’ prognosis in HNSCC.

Method.  Systematic searches of Medline, the Cochrane database of randomised controlled trials, Embase, review of conference abstracts and bibliographies of retrieved articles were performed. Studies were included if they; (1) considered biopsy proven primary HNSCC from the larynx, oropharynx, hypopharynx, or oral cavity. (2) Reported on the outcome following treatment that included radiotherapy, chemotherapy, surgery or a combination of these. (3) Attempted to assess p53 status and compared this with survival outcomes. (4) Measured survival outcomes at a minimum of 2 years post primary treatment. Primary outcome measures were overall survival (OS) and disease free survival (DFS). Hazard ratio (HR) with 95% confidence intervals (CI), was calculated from available data comparing outcome in mutant versus wild type p53 groups; initially for each study prior to aggregation.

Results.  205 papers were fully scrutinised, of these 36 were suitable for meta‐analysis. Larynx: OS HR = 1.00 (95% CI 0.82–1.22); DFS HR = 1.27 (95% CI 0.99–1.63). Oral Cavity: OS HR = 1.50 (95% CI 1.15–1.95), DFS HR = 1.46 (95% CI 1.12–1.91). Oropharynx: OS HR = 1.26 (95% CI 0.92–1.73), DFS HR = 0.45 (95% CI 0.28–0.73). Hypopharynx: OS HR = 1.59 (95% CI 1.07–2.35), no papers had sufficient information from which DFS results could be calculated.

Conclusions.  The results suggest a survival benefit for the p53 negative group, however there is marked heterogeneity between these studies, so any final conclusion should remain guarded.
Effect of conductive hearing loss on the activation pattern of the primary auditory cortex as assessed by functional MRI
Authors: Wild D.C. , Foster J.R. , Hall D.A.
Published: December 2008

Objectives.  To investigate the activation pattern of the human auditory cortex to monaural sound stimuli using functional magnetic resonance imaging (fMRI) in volunteers with normal hearing or unilateral conductive hearing loss.

Method.  Ten normal hearing volunteers and seven volunteers with unilateral conductive hearing loss were subjected to a random sequence of monaural sound stimuli and silence, whilst undergoing fMRI in a 3 Tesla scanner. The sound stimuli consisted of narrowband noise (250 Hz and 4000 Hz), as well as wideband noise (250–4000 Hz). A signal averaging algorithm was used to detect the response in the primary auditory cortex. A laterality index was calculated and compared between the study groups.

Results.  In the normal hearing group the auditory areas of both hemispheres showed activity in response to monaural stimuli, but the responses were consistently greater in the contralateral primary auditory cortex. Wideband stimuli produced the greatest degree of contralaterality and the largest response across the auditory cortex. The responses to high and low frequency stimuli were found to be conform with established tonotopic organization of the primary auditory cortex. There was no difference in the laterality index between the study groups.

Conclusions.  We have developed a non‐invasive way to investigate the response pattern of the primary auditory cortex to sound stimuli using fMRI. A similar activation pattern of the auditory cortex was found in both study groups suggesting a preservation of the organisation of the ascending auditory pathways and auditory cortex in unilateral conductive hearing loss.
Closure of nasal septal perforation: vertical mattress sutures to approximate bilateral advancement flaps
Authors: Wong S. , Raghavan U.
Published: December 2008

Objectives.  The aim of this study is to assess the closure success rate and symptoms control in the management of septal perforation using bilateral advancement flaps and porcine collagen.

Method.  In a prospective study, twenty‐eight patients underwent treatment for nasal septal perforation by the same surgeon in our institute between 2005 and 2007. Twelve were females and 16 were males with an average age of 45 years (range: 21–76). The mean follow up was 16 months (range: 6–24). The severity of symptoms was assessed pre and post‐operatively by the same assessor using the validated visual analogue score (VAS). The average vertical and horizontal diameters of the perforations were 22 mm (range: 10–35) and 27 mm (range: 10–37) respectively. The nasal valve angle was assessed pre, and post‐operatively by two independent assessors.

Results.  At the final follow up, there were statistically significant differences between the pre and post‐operative mean VAS scores in the open rhinoplasty group for epistaxis P < 0.0001, crusting P < 0.001, whistling P < 0.001 and nasal obstruction P < 0.002. One out of the 28 (4%) patients in this group had a 1×2 mm residual perforation but had significant symptoms improvement. Therefore, the closure success rate in the open rhinoplasty group was 96% despite a 100% improvement in relieving symptoms of epistaxis, crusting, and whistling, and a 92% nasal blockage symptom improvement.

Conclusions.  We conclude that the use of open rhinoplasty mucosal advancement flaps and porcine collagen sandwich may prove to be a pertinent and reliable alternative in the management of nasal septal perforation.
Exposure to environmental pollutants is related to sore throats and increased expression of HLA‐DQ in the upper airway mucosa of man
Authors: Rees L.E.N. , Jones P. , Pinkerton K. , Cogan T. , Ayling S.M. , Belafsky P. , Birchall M.A.
Published: December 2008

Objectives.  To determine the symptomatic and mucosal immune response to environmental pollution in UK population.

Methods.  We performed a prospective, matched questionnaire and laryngeal biopsy study in normal persons (n = 63). Subjects completed a validated health questionnaire. Levels of exposure to pollutants for the year prior to the study were determined via area‐based measurements of environmental particulates and composite air quality indices (CAQI). Quantitative multiple‐colour immunofluorescence was used to measure in vivo expression of antigens in laryngeal mucosal pinch biopsies: CD45 (RO, RC: leucocytes), CD4, CD8, CD79, (lymphocytes), MHC I, II (antigen presenting molecules). Multiple linear regression, correcting for age, was used to explore the relationship between dependent variables and pollution measures.

Results.  Complete data were available for 49 (questionnaire) and 54 (immunohistology) subjects. High levels of particulates and CAQI were associated with self‐reported frequent sore throats (P = 0.04 and 0.01, respectively), and with a trend towards increased asthma (P = 0.07 and 0.08). Dual HLA‐DQ (MHC II) and CD45 (leucocyte) expression by laryngeal epithelium was significantly correlated with levels of particulates (P = 0.03) and CAQI (P = 0.04). CAQI alone was significantly associated with CD4+ expression (P = 0.002).

Conclusions.  Pollution is known be associated with an increased prevalence of asthma, but this is the first report of an association with throat symptoms. We hypothesise that environmental pollution may contribute to pharyngeal inflammation by selective up‐regulation of the MHC Class II molecule, HLA‐DQ in epithelium and subsequent activation of leucocytes.
In vivo real time histology examination of the upper airway mucosa using confocal endomicroscopy
Authors: Hughes O.R. , Ayling S.M. , Birchall M.A.
Published: December 2008

Objectives.  We aim to establish whether in vivo confocal endomicroscopy (1) delivers a clear image of subcellular structures within the upper airway mucosa and (2) allows leucocytes to be identified using topical antibodies against CD45, the common leucocyte antigen.

Methods.  Endoscopic confocal images were captured from the supraglottic and tracheal mucosa in anaesthetised Landrace–Large white hybrid pigs using a rigid endoscope (Optiscan, Melbourne, Auctralia). 10% fluroscein was administered intravenously as contrast; 30 min later 0.05% acriflavine was applied as a topical contrast to the mucosa immediately prior to imaging of two pigs. In a further two pigs, 10% fluorescently labelled anti‐CD45 antibody was applied topically immediately prior to imaging. Images were captured and reviewed on a computer screen at the time of examination.

Results.  High‐resolution (x1000 magnification) images of the nuclei and cytoplasm of individual cells within the stratified squamous and respiratory epithelium of the supraglottis and trachea were captured using concurrent fluroscein and acriflavine staining. Intravenous fluroscein highlighted subsurface capillaries within which individual erythrocytes appeared as unstained shadows. Discrete leucocytes were clearly visible within the mucosa following topical application of anti‐CD45 antibody.

Conclusion.  In vivo confocal endomicroscopy allows examination of the upper airway mucosa at cellular resolution in real time. We have, for the first time, combined in vivo confocal imaging with antibody targeting of specific cell markers in the upper airway in large animals. Combining confocal endomicroscopy with topical antibodies against tumour markers (e.g. EGFR and p53) may allow tumours to be diagnosed and characterised during endoscopic examination without taking a biopsy.
Accuracy of diffusion‐weighted magnetic resonance imaging in the diagnosis of cholesteatoma
Authors: Khan S. , Rowlands R.G. , Benjamin E. , Abramovich S.
Published: December 2008

Objectives.  Recent interest has focused on various MRI techniques as a way of evaluating patients with cholesteatoma both pre‐ and post‐mastoidectomy.1,2 The aim of this study is to determine the role of diffusion‐weighted MRI imaging in detecting primary and recurrent cholesteatoma, and its accuracy in differentiating cholesteatoma from granulations and inflammatory tissue.

Methods.  We have designed a prospective pilot study evaluating whether diffusion‐weighted MRI imaging can accurately distinguish cholesteatoma from inflammatory tissue and fluid within the middle ear and mastoid cavity. We have established a database of consecutive patients placed on the waiting list for mastoidectomy and compared the preoperative reports with the perioperative findings during mastoidectomy. Outcomes were the presence or otherwise of cholesteatoma.

Results.  Between April and December 2007, 15 patients underwent preoperative ECHO planar MRI imaging and tympanomastoidectomy. Cholesteatoma was identified in six patients at time of surgery. This had been identified preoperatively on diffusion MRI scanning in five patients. In nine patients who did not have cholesteatoma at time of surgery all had negative preoperative scans. The MRI scans had a sensitivity and specificity of 83% and 100%, respectively.

Conclusions.  We have demonstrated that diffusion‐weighted MRI imaging may be useful in the diagnosis and confirmation of cholesteatoma. In particular, a negative diffusion‐weighted scan can almost certainly exclude the presence of cholesteatoma. This technique may be particularly valuable following canal‐wall up mastoid surgery thus avoiding the requirement for a second‐look procedure, on those patients whose postoperative hearing thresholds are satisfactory and do not require ossiculoplasty.

References.  1 Vercruysse J.P., De Foer B., Pouillon M. et al. (2006) The value of diffusion‐weighted MR imaging in the diagnosis of primary acquired and residual cholesteatoma: a surgical verified study of 100 patients. Eur. Radiol. 16, 1461–1467

2 Stasolla A., Magluilo G., Parrotto D. et al. (2004) Detection of postoperative relapsing/residual cholesteatoma with diffusion‐weighted echo‐planar magnetic resonance imaging. Otol. Neurotol. 25, 879–884
On the Molecular Etiology of Cornelia de Lange Syndrome
Authors: Dorsett Dale , Krantz Ian D.
Published: December 2008

Cornelia de Lange syndrome (CdLS) is genetically heterogeneous and is usually sporadic, occurring approximately once per 10,000 births. CdLS individuals display diverse and variable deficits in growth, mental development, limbs, and organs. In the past few years it has been shown that CdLS is caused by gene mutations affecting proteins involved in sister chromatid cohesion. Studies in model organisms, and more recently in human cells, have revealed, somewhat unexpectedly, that the developmental deficits in CdLS likely arise from changes in gene expression. The mechanisms by which cohesion factors regulate gene expression remain to be elucidated, but current data suggest that they likely regulate transcription in multiple ways.
Combined Tarsal and Carpal Tunnel Syndrome in Mucolipidosis Type III
Authors: Smuts Izelle , Potgieter Denise , Van Der Westhuizen Francois Hendrikus
Published: December 2008

Mucolipidosis type III (MLIII) (MIM# 252600) is an uncommon autosomal recessive disorder that results from uridine 5′‐diphosphate‐N‐acetylglucosamine: lysosomal hydrolase N‐acetyl‐1‐phosphotransferase or UDP‐GlcNAc 1‐phophotransferase deficiency. Clinical manifestations include developmental delay, short stature and other structural abnormalities. Less common clinical features, such as carpal tunnel syndrome, claw hand deformities, trigger fingers, and claw toes have previously been reported, but no specific association with tarsal tunnel syndrome has been reported in the literature. Tarsal tunnel syndrome is caused by entrapment of the posterior tibialis nerve in the tunnel formed by the medial malleolus of the ankle and the flexor retinaculum. It causes pain in the heel and sole of the foot as well as abnormal sensation in the distribution area of nervus tibialis posterior. In adults, the most common cause described is a ganglion. The phenomenon is rare in children and the published series are small. This case report portrays the presentation of a young girl with breath‐holding spells secondary to painful bilateral tarsal tunnel syndrome and trigger fingers subsequently diagnosed with MLIII.
Chimerism in Black Southern African Patients with True Hermaphroditism 46,XX/47XY,+21 and 46,XX/46,XY
Authors: Ramsay M. , Pfaffenzeller W. , Kotze E. , Bhengu L. , Essop F. , De Ravel T.
Published: December 2008

True hermaphroditism is defined by the presence of both testicular and ovarian tissue in an individual. True hermaphrodites usually present at birth with ambiguous genitalia, and subsequent invasive investigations are needed to confirm the diagnosis. Several large cohorts of black South Africans with true hermaphroditism have been described, and by far the majority of those investigated had a 46,XX karyotype, with absence of the SRY sequence. This paper represents the first report of the molecular investigation of mosiacism/chimerism as the cause of hermaphroditism in black southern African patients. It is the second report worldwide of a 46,XX/47,XY,+21 chimera, with the first described in a Japanese infant in 1994. Case 1 in the present study is a child who is a 46,XX/47,XY,+21 tetragametic chimera. Molecular studies revealed two paternal and two maternal alleles at four of ten STR loci investigated and three alleles at four of these loci. The young boy exhibited no features of Down syndrome, other than a unilateral single palmar crease. Cases 2 and 3 both have a 46,XX/46,XY karyotype. Chimerism is supported by molecular analysis in Case 2, and molecular studies were not done for Case 3.
Nuclear and Mitochondrial Genome Defects in Autisms
Authors: Smith Moyra , Spence M. Anne , Flodman Pamela
Published: December 2008

In this review we will evaluate evidence that altered gene dosage and structure impacts neurodevelopment and neural connectivity through deleterious effects on synaptic structure and function, and evidence that the latter are key contributors to the risk for autism. We will review information on alterations of structure of mitochondrial DNA and abnormal mitochondrial function in autism and indications that interactions of the nuclear and mitochondrial genomes may play a role in autism pathogenesis. In a final section we will present data derived using Affymetrixtm SNP 6.0 microarray analysis of DNA of a number of subjects and parents recruited to our autism spectrum disorders project. We include data on two sets of monozygotic twins. Collectively these data provide additional evidence of nuclear and mitochondrial genome imbalance in autism and evidence of specific candidate genes in autism. We present data on dosage changes in genes that map on the X chromosomes and the Y chromosome. Precise analyses of Y located genes are often difficult because of the high degree of homology of X‐ and Y‐related genes. However, continued efforts to analyze the latter are important, given the consistent evidence for a 4:1 ratio of males to females affected by autism. It is also important to consider whether environmental factors play a role in generating the nuclear and mitochondrial genomic instability we have observed. The study of autism will benefit from a move to analysis of pathways and multigene clusters for identification of subtypes that share a specific genetic etiology.
Genetic Calcium Signaling Abnormalities in the Central Nervous System: Seizures, Migraine, and Autism
Authors: Gargus J. Jay
Published: December 2008

The calcium ion is one of the most versatile, ancient, and universal of biological signaling molecules, known to regulate physiological systems at every level from membrane potential and ion transporters to kinases and transcription factors. Disruptions of intracellular calcium homeostasis underlie a host of emerging diseases, the calciumopathies. Cytosolic calcium signals originate either as extracellular calcium enters through plasma membrane ion channels or from the release of an intracellular store in the endoplasmic reticulum (ER) via inositol triphosphate receptor and ryanodine receptor channels. Therefore, to a large extent, calciumopathies represent a subset of the channelopathies, but include regulatory pathways and the mitochondria, the major intracellular calcium repository that dynamically participates with the ER stores in calcium signaling, thereby integrating cellular energy metabolism into these pathways, a process of emerging importance in the analysis of the neurodegenerative and neuropsychiatric diseases. Many of the calciumopathies are common complex polygenic diseases, but leads to their understanding come most prominently from rare monogenic channelopathy paradigms. Monogenic forms of common neuronal disease phenotypes—such as seizures, ataxia, and migraine—produce a constitutionally hyperexcitable tissue that is susceptible to periodic decompensations. The gene families and genetic lesions underlying familial hemiplegic migraine, FHM1/CACNA1A, FHM2/ATP1A2, and FHM3/SCN1A, and monogenic mitochondrial migraine syndromes, provide a robust platform from which genes, such as CACNA1C, which encodes the calcium channel mutated in Timothy syndrome, can be evaluated for their role in autism and bipolar disease.
Clinical Utility of Array CGH for the Detection of Chromosomal Imbalances Associated with Mental Retardation and Multiple Congenital Anomalies
Authors: Edelmann Lisa , Hirschhorn Kurt
Published: December 2008

Microarray‐based comparative genomic hybridization (array CGH) has revolutionized clinical cytogenetics, as it provides a relatively quick method to scan the genome for gains and losses of chromosomal material with significantly higher resolution and greater clinical yield than was previously possible. A number of different array CGH platforms have emerged and are being used successfully in the diagnostic setting. In the past few years, these new methodologies have led to the identification of novel genomic disorders in patients with developmental delay/mental retardation and/or multiple congenital anomalies (DD/MR/MCA) as well as the discovery that each individual carries inherited copy number variations (CNV) whose contributions to genetic variation and complex disease are not yet well understood. Although array CGH is currently being used as an adjunct test to standard karyotype analysis, it is likely to become the genetic test of choice, especially in cases of idiopathic MR/MCA.
Common garden comparisons of native and introduced plant populations: latitudinal clines can obscure evolutionary inferences
Authors: Colautti Robert I. , Maron John L. , Barrett Spencer C. H.
Published: December 2008

Common garden studies are increasingly used to identify differences in phenotypic traits between native and introduced genotypes, often ignoring sources of among‐population variation within each range. We re‐analyzed data from 32 common garden studies of 28 plant species that tested for rapid evolution associated with biological invasion. Our goals were: (i) to identify patterns of phenotypic trait variation among populations within native and introduced ranges, and (ii) to explore the consequences of this variation for how differences between the ranges are interpreted. We combined life history and physiologic traits into a single principal component (PCALL) and also compared subsets of traits related to size, reproduction, and defense (PCSIZE, PCREP, and PCDEF, respectively). On average, introduced populations exhibited increased growth and reproduction compared to native conspecifics when latitude was not included in statistical models. However, significant correlations between PC‐scores and latitude were detected in both the native and introduced ranges, indicating population differentiation along latitudinal gradients. When latitude was explicitly incorporated into statistical models as a covariate, it reduced the magnitude and reversed the direction of the effect for PCALL and PCSIZE. These results indicate that unrecognized geographic clines in phenotypic traits can confound inferences about the causes of evolutionary change in invasive plants.
PERSPECTIVE: Principles of ecological immunology
Authors: Sadd Ben M. , Schmid‐Hempel Paul
Published: December 2008

Defending self against nonself is a major problem in a world in which individuals are under constant pressure from parasites that gain fitness benefits at a cost to their host. Defences that have evolved are diverse, and range from behavioural adaptations to physiochemical barriers. The immune defence is a final line of protection and is therefore of great importance. Given this importance, variability in immune defence would seem counterintuitive, yet that is what is observed. Ecological immunology attempts to explain this variation by invoking costs and trade‐offs, and in turn proposing that the optimal immune defence will vary over environments. Studies in this field have been highly successful in establishing an evolutionary ecology framework around immunology. However, in order enrich our understanding of this area, it is perhaps time to broaden the focus to include parasites as more than simply elicitors of immune responses. In essence, to view immunity as produced by the host, the environment, and the active involvement of parasites.
The Danish Cartoon Controversy and the Exclusivist Turn in European Civic Nationalism
Authors: Kahn Robert A.
Published: December 2008

The Danish cartoon controversy raises questions about the inclusiveness of Western European civic nationalism. The controversy highlighted a harsh, exclusivist brand of Danish civic nationalism that cast Muslim migrants as outsiders. The controversy also saw a broader group of cartoon supporters from across Europe fault Muslims for failing to respect liberal traditions of freedom of speech and secularism, traditions now explicitly labeled ‘European’. However, others pushed the debate in a more open direction by defending the Jyllands Posten's freedom of expression in ethnically neutral terms and explicitly challenging the contrast between an enlightened Europe and an intolerant Muslim other.
Forging the Nepali Nation through Law: A Reflection on the Use of Western Legal Tools in a Himalayan Kingdom
Authors: Malagodi Mara
Published: December 2008

The present article endeavours to analyse the use and scope of Western positivistic legal tools in the creation of the Nepali nation. It suggests a two‐level analysis. First, a historical analysis of Nepal's political and legal developments is presented to investigate the rationale of using law as a social engineering and homogenising tool promoting an identifiably Nepali national identity. Second, the article focuses on the current debates concerning constitutional change in Nepal. The debates about the demise of the 1990 Constitution in 2007, and the election of a Constituent Assembly need to be investigated in the light of the growing politicisation of ethnicity in the country. The overarching demand for inclusion stems from the discontent of Nepal's ethno‐linguistic, religious, and regional minorities with their historical subordination. Ultimately, the article aims to demonstrate that the Nepali experience is situated somewhere between the civic and ethnic models of nationalism Kohn enunciated.
Building a Nation in Rwanda? De‐ethnicisation and its Discontents
Authors: Purdeková Andrea
Published: December 2008

Rwanda remains in the eastern camp of ethnic ideas and projects of a ‘nation’ inasmuch as it is dominated by cultural as opposed to civic/political elements. Although the Rwandan attempt remains exclusive internally, it does not affirm the validity of an idealised Kohnian dichotomy between ‘exclusive’ ethnic nationalism and ‘inclusive’ civic nationalism. To avoid the trap of a bi‐polar and value‐ladden division, while preserving the useful insights of Kohn, the paper calls for a re‐conceptualisation of nation‐building projects along the continuum of their relative inclusiveness/exclusiveness, both internally (who shapes the ‘idea of nation’) and externally (the boundaries of nation).
The Relevance of Kohn's Dichotomy to the Russian Nineteenth‐Century Concept of Nationalism
Authors: Rabow‐Edling Susanna
Published: December 2008

This article challenges the common distinction between a Western and an Eastern type of nationalism with regard to Russian nationalism. Analysing the civic nationalism of the Decembrists and the cultural nationalism of the Slavophiles, it argues that the type of nationalism that appears in a specific country has more to do with timing than with place or social conditions. The article also suggests that intellectual thought should be studied in an international rather than a national context and that the world of ideas has to be granted a considerable degree of autonomy from socioeconomic conditions.
Notes on the genus Crataegus (Rosaceae–Pyreae) in southern Europe, the Crimea and western Asia
Authors: Christensen Knud Ib , Zieliński Jerzy
Published: December 2008

The infrageneric classification of Crataegus azarolus is revised, and a new combination is proposed, C. azarolus var. assadii comb. et stat. nov. Crataegus monogyna var. lasiocarpa is reinstalled as the correct varietal name for the hairy, Mediterranean form of C. monogyna. Crataegus granatensis is shown to be synonymous with C. monogyna var. monogyna and not with C. nevadensis which is a species more closely related to C. rhipidophylla, C. microphylla and C. pseudoheterophylla than to C. monogyna. Crataegus rhipidophylla var. ronnigeri is reported as new to Bulgaria and its occurrence in the Crimea is confirmed. Crataegus×bornmuelleri nothosp. nov. (C. orientalis×tanacetifolia) and C.×inexpectans nothosp. nov. (C. monogyna×nevadensis) are described anew. Emended descriptions and new records are supplied for Crataegus nevadensis, C.×browicziana (C. microphylla×rhipidophylla), C.×sinaica (C. azarolus×monogyna), and C.×yosgatica (C. monogyna×tanacetifolia). Crataegus×sinaica is reported as new to Greece. New records are given for Crataegus×rubrinervis (C. monogyna×pentagyna) and C.×subsphaericea (C. monogyna×rhipidophylla).
A negative interaction between brainstem and peripheral respiratory chemoreceptors modulates peripheral chemoreflex magnitude
Authors: Day Trevor A. , Wilson Richard J. A.
Published: December 2008

Interaction between central (brainstem) and peripheral (carotid body) respiratory chemosensitivity is vital to protect blood gases against potentially deleterious fluctuations, especially during sleep. Previously, using an in situ arterially perfused, vagotomized, decerebrate preparation in which brainstem and peripheral chemoreceptors are perfused separately (i.e. dual perfused preparation; DPP), we observed that the phrenic response to specific carotid body hypoxia was larger when the brainstem was held at 25 Torr P compared to 50 Torr P. This suggests a negative (i.e. hypo‐additive) interaction between chemoreceptors. The current study was designed to (a) determine whether this observation could be generalized to all carotid body stimuli, and (b) exclude the possibility that the hypo‐additive response was the simple consequence of ventilatory saturation at high brainstem P. Specifically, we tested how steady‐state brainstem P modulates peripheral chemoreflex magnitude in response to carotid body P and P perturbations, both above and below eupnoeic levels. We found that the peripheral chemoreflex was more responsive the lower the brainstem P regardless of whether the peripheral chemoreceptors received stimuli which increased or decreased activation. These findings demonstrate a negative interaction between brainstem and peripheral chemosensitivity in the rat in the absence of ventilatory saturation. We suggest that a negative interaction in humans may contribute to increased controller gain associated with sleep‐related breathing disorders and propose that the assumption of simple addition between chemoreceptor inputs used in current models of the respiratory control system be reconsidered.
Synaptic ionotropic glutamate receptors and plasticity are developmentally altered in the CA1 field of Fmr1 knockout mice
Authors: Pilpel Yair , Kolleker Aleksander , Berberich Sven , Ginger Melanie , Frick Andreas , Mientjes Edwin , Oostra Ben A. , Seeburg Peter H.
Published: December 2008

Fragile X syndrome is one of the most common forms of mental retardation, yet little is known about the physiological mechanisms causing the disease. In this study, we probed the ionotropic glutamate receptor content in synapses of hippocampal CA1 pyramidal neurons in a mouse model for fragile X (Fmr1 KO2). We found that Fmr1 KO2 mice display a significantly lower AMPA to NMDA ratio than wild‐type mice at 2 weeks of postnatal development but not at 6–7 weeks of age. This ratio difference at 2 weeks postnatally is caused by down‐regulation of the AMPA and up‐regulation of the NMDA receptor components. In correlation with these changes, the induction of NMDA receptor‐dependent long‐term potentiation following a low‐frequency pairing protocol is increased in Fmr1 KO2 mice at this developmental stage but not later in maturation. We propose that ionotropic glutamate receptors, as well as potentiation, are altered at a critical time point for hippocampal network development, causing long‐term changes. Associated learning and memory deficits would contribute to the fragile X mental retardation phenotype.
Physiological properties of direction‐selective ganglion cells in early postnatal and adult mouse retina
Authors: Chen Minggang , Weng Shijun , Deng Qiudong , Xu Zhen , He Shigang
Published: December 2008

Selective responses of retinal ganglion cells (RGCs) to the direction of motion have been recorded extracellularly from the rabbit and the mouse retina at eye opening. Recently, it has been shown that the development of this circuitry is light independent. Using whole‐cell patch clamp recording, we report here that mouse early postnatal direction‐selective ganglion cells (DSGCs) showed lower membrane excitability, lower reliability of synaptic transmission and much slower kinetics of light responses compared with adult DSGCs. However, the degree of direction selectivity of early postnatal DSGCs measured by the direction‐selective index and the width of the directional tuning curve was almost identical to that of adult DSGCs. The DSGCs exhibited a clear selectivity for the direction of motion at the onset of light sensitivity. Furthermore, the degree of direction selectivity was not affected by rearing in complete darkness from birth to postnatal day 11 or 30. The formation of the retinal neurocircuitry for coding motion direction is completely independent of light.
Maternal nutritional history predicts obesity in adult offspring independent of postnatal diet
Authors: Howie G. J. , Sloboda D. M. , Kamal T. , Vickers M. H.
Published: December 2008

Significant alterations in maternal nutrition may induce long‐term metabolic consequences in offspring, in particular obesity and leptin and insulin resistance. Although maternal nutrient deprivation has been well characterized in this context, there is a relative paucity of data on how high fat (HF) nutrition impacts on the subsequent generation. The present study investigated the effects of maternal HF nutrition either throughout the mother's life up to and including pregnancy and lactation or HF nutrition restricted to pregnancy and lactation, on growth and metabolic parameters in male and female offspring. Virgin Wistar rats were assigned to one of three experimental groups: (1) controls (Cont): dams fed a standard chow diet throughout their life and throughout pregnancy and lactation; (2) maternal high fat (MHF) group: dams fed a HF diet from weaning up to and throughout pregnancy and lactation; and (3) pregnancy and lactation high fat (PLHF): dams fed a chow diet through their life until conception and then fed a HF diet throughout pregnancy and lactation. At weaning, all offspring were fed either a chow or HF diet for the remainder of the study (160 days). Litter size and sex ratios were not significantly different between the groups. MHF and PLHF offspring had significantly lower body weights and were hypoleptinaemic and hypoinsulinaemic at birth compared to Cont offspring. As adults however, chow‐fed MHF and PLHF offspring were significantly more obese than Cont offspring (DEXA scanning at day 150, P < 0.001 for maternal HF diet). As expected a postweaning HF diet resulted in increased adiposity in all groups; MHF and PLHF offspring, however, always remained significantly more obese than Cont offspring. Increased adiposity in MHF and PLHF offspring was paralleled by hyperinsulinaemia and hyperleptinaemia (P < 0.001; MHF and PLHF versus Cont). It is of interest that a lifetime of HF nutrition produced a similar offspring phenotype to HF nutrition restricted to pregnancy and lactation alone, thus suggesting that the postnatal sequelae of maternal HF nutrition occurs independent of preconceptional diet. These data further reinforce the importance of maternal nutrition during these critical windows of development and show that maternal HF feeding can induce a markedly obese phenotype in male and female offspring completely independent of postnatal nutrition.
Neuronal oscillations and the rate‐to‐phase transform: mechanism, model and mutual information
Authors: McLelland Douglas , Paulsen Ole
Published: December 2008

Theoretical and experimental studies suggest that oscillatory modes of processing play an important role in neuronal computations. One well supported idea is that the net excitatory input during oscillations will be reported in the phase of firing, a ‘rate‐to‐phase transform’, and that this transform might enable a temporal code. Here, we investigate the efficiency of this code at the level of fundamental single cell computations. We first develop a general framework for the understanding of the rate‐to‐phase transform as implemented by single neurons. Using whole cell patch‐clamp recordings of rat hippocampal pyramidal neurons in vitro, we investigated the relationship between tonic excitation and phase of firing during simulated theta frequency (5 Hz) and gamma frequency (40 Hz) oscillations, over a range of physiological firing rates. During theta frequency oscillations, the phase of the first spike per cycle was a near‐linear function of tonic excitation, advancing through a full 180 deg, from the peak to the trough of the oscillation cycle as excitation increased. In contrast, this relationship was not apparent for gamma oscillations, during which the phase of firing was virtually independent of the level of tonic excitatory input within the range of physiological firing rates. We show that a simple analytical model can substantially capture this behaviour, enabling generalization to other oscillatory states and cell types. The capacity of such a transform to encode information is limited by the temporal precision of neuronal activity. Using the data from our whole cell recordings, we calculated the information about the input available in the rate or phase of firing, and found the phase code to be significantly more efficient. Thus, temporal modes of processing can enable neuronal coding to be inherently more efficient, thereby allowing a reduction in processing time or in the number of neurons required.
Characteristics and function of cardiac mitochondrial nitric oxide synthase
Authors: Dedkova Elena N. , Blatter Lothar A.
Published: December 2008

We used laser scanning confocal microscopy in combination with the nitric oxide (NO)‐sensitive fluorescent dye DAF‐2 and the reactive oxygen species (ROS)‐sensitive dyes CM‐H2DCF and MitoSOX Red to characterize NO and ROS production by mitochondrial NO synthase (mtNOS) in permeabilized cat ventricular myocytes. Stimulation of mitochondrial Ca2+uptake by exposure to different cytoplasmic Ca2+concentrations ([Ca2+]i= 1, 2 and 5 μm) resulted in a dose‐dependent increase of NO production by mitochondria whenl‐arginine, a substrate for mtNOS, was present. Collapsing the mitochondrial membrane potential with the protonophore FCCP or blocking the mitochondrial Ca2+uniporter with Ru360 as well as blocking the respiratory chain with rotenone or antimycin A in combination with oligomycin inhibited mitochondrial NO production. In the absence ofl‐arginine, mitochondrial NO production during stimulation of Ca2+uptake was significantly decreased, but accompanied by increase in mitochondrial ROS production. Inhibition of mitochondrial arginase to limitl‐arginine availability resulted in 50% inhibition of Ca2+‐induced ROS production. Both mitochondrial NO and ROS production were blocked by the nNOS inhibitor (4S)‐N‐(4‐amino‐5[aminoethyl]aminopentyl)‐N′‐nitroguanidine and the calmodulin antagonist W‐7, while the eNOS inhibitorl‐N5‐(1‐iminoethyl)ornithine (l‐NIO) or iNOS inhibitorN‐(3‐aminomethyl)benzylacetamidine, 2HCl (1400W) had no effect. The superoxide dismutase mimetic and peroxynitrite scavenger MnTBAP abolished Ca2+‐induced ROS generation and increased NO production threefold, suggesting that in the absence of MnTBAP either formation of superoxide radicals suppressed NO production or part of the formed NO was transformed quickly to peroxynitrite. In the absence ofl‐arginine, mitochondrial Ca2+uptake induced opening of the mitochondrial permeability transition pore (PTP), which was blocked by the PTP inhibitor cyclosporin A and MnTBAP, and reversed byl‐arginine supplementation. In the presence of the mtNOS cofactor (6R)‐5,6,7,8,‐tetrahydrobiopterin (BH4; 100 μm) mitochondrial ROS generation and PTP opening decreased while mitochondrial NO generation slightly increased. These data demonstrate that mitochondrial Ca2+uptake activates mtNOS and leads to NO‐mediated protection against opening of the mitochondrial PTP, provided sufficient availability ofl‐arginine and BH4. In conclusion, our data show the importance ofl‐arginine and BH4for cardioprotection via regulation of mitochondrial oxidative stress and modulation of PTP opening by mtNOS.
Minimization of Friction Influence on the Evaluation of Rheological Parameters From Compression Test: Application to a Forging Steel Behavior Identification
Authors: Diot S. , Guines D. , Gavrus A. , Ragneau E.
Published: December 2008

In order to characterize the metal behavior at strain, strain rate, and temperature range encountered in metal forming processes, the rheological compressive test is well adapted and has been often used. Nevertheless, this experimental test is more complicated to realize than the extension one and requires some particular considerations owing to the friction condition occurring between the specimen and the dies. This paper deals with a new specimen shape proposed to realize both static and dynamic compression tests. The independence of the material parameters to die friction is highlighted by means of a pseudo-experimental validation. The proposed specimen shape is validated by compression tests carried out on a 50CD4 steel (norm EN 10 083). The choice of the mathematical form of the constitutive law allowing to characterize its behavior at strains, strain rates, and temperatures corresponding to an extrusion application is then discussed. To replicate more accurately the nonuniformity of the different fields in the specimen, a classical inverse procedure consisting in coupling a finite element model of the compression test with an optimization module is used to determined the rheological parameters.