15q11.2 CNV affects cognitive, structural and functional correlates of dyslexia and dyscalculia.

Several copy number variants have been associated with neuropsychiatric disorders and these variants have been shown to also influence cognitive abilities in carriers unaffected by psychiatric disorders. Previously, we associated the 15q11.2(BP1-BP2) deletion with specific learning disabilities and a larger corpus callosum. Here we investigate, in a much larger sample, the effect of the 15q11.2(BP1-BP2) deletion on cognitive, structural and functional correlates of dyslexia and dyscalculia. We report that the deletion confers greatest risk of the combined phenotype of dyslexia and dyscalculia. We also show that the deletion associates with a smaller left fusiform gyrus. Moreover, tailored functional magnetic resonance imaging experiments using phonological lexical decision and multiplication verification tasks demonstrate altered activation in the left fusiform and the left angular gyri in carriers. Thus, by using convergent evidence from neuropsychological testing, and structural and functional neuroimaging, we show that the 15q11.2(BP1-BP2) deletion affects cognitive, structural and functional correlates of both dyslexia and dyscalculia.

First outbreak of linezolid-resistant vancomycin-resistant Enterococcus faecium in an Irish hospital, February to September 2014.

An outbreak of linezolid-resistant vancomycin-resistant Enterococcus faecium (LRVREfm) occurred in the hepatology ward of a tertiary referral hospital in Ireland between February and September 2014. LRVREfm was isolated from 15 patients; pulsed-field gel electrophoresis confirmed spread of a single clone. This is the first report of an outbreak of linezolid-resistant vancomycin-resistant enterococcus in Ireland.

Ketamine induces a robust whole-brain connectivity pattern that can be differentially modulated by drugs of different mechanism and clinical profile.

Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has been studied in relation to the glutamate hypothesis of schizophrenia and increases dissociation, positive and negative symptom ratings. Ketamine effects brain function through changes in brain activity; these activity patterns can be modulated by pre-treatment of compounds known to attenuate the effects of ketamine on glutamate release. Ketamine also has marked effects on brain connectivity; we predicted that these changes would also be modulated by compounds known to attenuate glutamate release. Here, we perform task-free pharmacological magnetic resonance imaging (phMRI) to investigate the functional connectivity effects of ketamine in the brain and the potential modulation of these effects by pre-treatment of the compounds lamotrigine and risperidone, compounds hypothesised to differentially modulate glutamate release. Connectivity patterns were assessed by combining windowing, graph theory and multivariate Gaussian process classification. We demonstrate that ketamine has a robust effect on the functional connectivity of the human brain compared to saline (87.5 % accuracy). Ketamine produced a shift from a cortically centred, to a subcortically centred pattern of connections. This effect is strongly modulated by pre-treatment with risperidone (81.25 %) but not lamotrigine (43.75 %). Based on the differential effect of these compounds on ketamine response, we suggest the observed connectivity effects are primarily due to NMDAR blockade rather than downstream glutamatergic effects. The connectivity changes contrast with amplitude of response for which no differential effect between pre-treatments was detected, highlighting the necessity of these techniques in forming an informed view of the mechanistic effects of pharmacological compounds in the human brain.

Microbial community structure during fluoranthene degradation in the presence of plants.

AIMS: To investigate bacterial and fungal community structure during degradation of varying concentrations (0-5000 mg kg(-1) ) of the polycyclic aromatic hydrocarbon (PAH) fluoranthene in the presence or absence of tomato plants. METHOD AND RESULTS: Fluoranthene amended or unamended growing media, with or without a plant, were incubated in pots in a glasshouse for 30 days. Fluoranthene concentration was quantified using GC-FID, while bacterial and fungal community structure was investigated using trflp and arisa, respectively. The abundance of two ring hydroxylating dioxygenase genes was measured using qPCR. More fluoranthene was degraded in the presence of tomato plants at 500 and 5000 mg fluoranthene kg(-1) (P < 0·001), and it had a toxic effect on plant growth. Bacterial and fungal community composition in the rhizosphere was significantly different from that in nonrhizospheric and unplanted samples. The influence of fluoranthene on bacterial communities overcame that of the plant root such that community composition in rhizosphere and planted nonrhizospheric samples was broadly similar when fluoranthene was present. PAH-RHDα-GP genes were more abundant than PAH-RHDα-GN genes in all treatments. PAH-RHDα-GN abundance was unaffected by either PAH concentration or growing medium type, while the abundance of PAH-RHDα-GP was greatest in the rhizosphere. CONCLUSIONS: Plants promoted microbial growth and diversity and led to increases in abundance of Gram-positive dioxygenase genes, correlated with increased degradation of fluoranthene. SIGNIFICANCE AND IMPACT OF THE STUDY: This work contributes to knowledge in the broad area of biodegradation and also provides useful information for the design of future bioremediation strategies.

Well-being in pregnancy: an examination of the effect of socioeconomic, dietary and lifestyle factors including impact of a low glycaemic index dietary intervention.

BACKGROUND/OBJECTIVE: Well-being has been linked to the quality of diet and lifestyle in adults; however, there is a paucity of data in pregnancy. The aim of this study was to examine the relationship between well-being and socioeconomic status, diet and lifestyle during pregnancy and to consider the effect of intervention with low glycaemic index (GI) diet on well-being. SUBJECTS/METHODS: This was a cohort analysis of 619 participants of the ROLO study (Randomised cOntrol trial of LOw GI diet versus no dietary intervention to prevent recurrence of fetal macrosomia). The following data were collected: educational attainment, dietary intakes (food frequency questionnaire), physical activity (self-reported) and well-being (WHO-5-Item Wellbeing Index--expressed as a percentage). RESULTS: Well-being was positively associated with education and physical activity. Third-level education was associated with a 3.07-point higher well-being percentage score, and each day that an individual achieved >30 min walking per week was associated with a 1.10-point increase in percentage well-being score, Radj(2) 2.4% (F=7.260, P=0.001). The intervention low GI group had a significantly lower percentage well-being score than the usual diet group (56.3% vs 59.9%, P=0.015). No correlation was noted between well-being and GI status calculated from food diaries (P=0.469). Well-being was not associated with micronutrient intake. CONCLUSIONS: Well-being in pregnancy was independently and positively associated with education and physical activity and negatively associated with low GI dietary intervention. These findings have significance not only for women at risk of low mood but also for healthcare professionals when counselling women about the importance of healthy lifestyle in pregnancy.

Multivariate decoding of brain images using ordinal regression.

Neuroimaging data are increasingly being used to predict potential outcomes or groupings, such as clinical severity, drug dose response, and transitional illness states. In these examples, the variable (target) we want to predict is ordinal in nature. Conventional classification schemes assume that the targets are nominal and hence ignore their ranked nature, whereas parametric and/or non-parametric regression models enforce a metric notion of distance between classes. Here, we propose a novel, alternative multivariate approach that overcomes these limitations - whole brain probabilistic ordinal regression using a Gaussian process framework. We applied this technique to two data sets of pharmacological neuroimaging data from healthy volunteers. The first study was designed to investigate the effect of ketamine on brain activity and its subsequent modulation with two compounds - lamotrigine and risperidone. The second study investigates the effect of scopolamine on cerebral blood flow and its modulation using donepezil. We compared ordinal regression to multi-class classification schemes and metric regression. Considering the modulation of ketamine with lamotrigine, we found that ordinal regression significantly outperformed multi-class classification and metric regression in terms of accuracy and mean absolute error. However, for risperidone ordinal regression significantly outperformed metric regression but performed similarly to multi-class classification both in terms of accuracy and mean absolute error. For the scopolamine data set, ordinal regression was found to outperform both multi-class and metric regression techniques considering the regional cerebral blood flow in the anterior cingulate cortex. Ordinal regression was thus the only method that performed well in all cases. Our results indicate the potential of an ordinal regression approach for neuroimaging data while providing a fully probabilistic framework with elegant approaches for model selection.

Quantifying the attenuation of the ketamine pharmacological magnetic resonance imaging response in humans: a validation using antipsychotic and glutamatergic agents.

Ketamine acts as an N-methyl-D-aspartate receptor antagonist and evokes psychotomimetic symptoms resembling schizophrenia in healthy humans. Imaging markers of acute ketamine challenge have the potential to provide a powerful assay of novel therapies for psychiatric illness, although to date this assay has not been fully validated in humans. Pharmacological magnetic resonance imaging (phMRI) was conducted in a randomized, placebo-controlled crossover design in healthy volunteers. The study comprised a control and three ketamine infusion sessions, two of which included pretreatment with lamotrigine or risperidone, compounds hypothesized to reduce ketamine-induced glutamate release. The modulation of the ketamine phMRI response was investigated using univariate analysis of prespecified regions and a novel application of multivariate analysis across the whole-brain response. Lamotrigine and risperidone resulted in widespread attenuation of the ketamine-induced increases in signal, including the frontal and thalamic regions. A contrasting effect across both pretreatments was observed only in the subgenual prefrontal cortex, in which ketamine produced a reduction in signal. Multivariate techniques proved successful in both classifying ketamine from placebo (100%) and identifying the probability of scans belonging to the ketamine class (ketamine pretreated with placebo: 0.89). Following pretreatment, these predictive probabilities were reduced to 0.58 and 0.49 for lamotrigine and risperidone, respectively. We have provided clear demonstration of a ketamine phMRI response and its attenuation with both lamotrigine and risperidone. The analytical methodology used could be readily applied to investigate the mechanistic action of novel compounds relevant for psychiatric disorders such as schizophrenia and depression.

First Report of Gladiolus Corm Rot Caused by Fusarium proliferatum in Oman.

Hybrid gladiolus varieties have potential as a major ornamental crop in Oman. Grown for the cut-flower industry, their production has increased significantly in recent years. In 2010, during a field trial of two hybrid varieties (Red Majesty and Mascagni) grown in sandy soil at Al Moballah, Muscat, approximately 3% of Red Majesty plants and 12% of Mascagni plants showed signs of wilting and yellowing prior to plant death. In all cases, tissue taken from 20 diseased corms yielded Fusarium-like colonies on potato dextrose agar (PDA). Colonies were light to dark purple in color with dense and abundant aerial mycelium; macroconidia were 33.8 × 4.8 µm with 3 to 5 septa per spore; microconidia were 13.5 × 4.8 µm with 0 to 1 septa per spore and were in chains (mean of 50 spores in both cases). No chlamydospores were observed. In vitro characters and spore measurements conformed to previously described features of Fusarium proliferatum (Matsushima) Nirenberg (2). Mycelial plugs (5 mm in diameter) were taken from 5-day-old cultures of F. proliferatum grown on 2.5% PDA and wrapped on the base of Gladiolus corms using Parafilm and wet cotton. The Parafilm was removed after 7 days of inoculation. The corms were kept in moistened polythene bags for and symptoms were recorded. Control corms were inoculated using PDA (1). Artificial inoculations resulted in rot symptoms on all corms within 14 days and fungal colonies identical to initial isolations were recovered from artificially infected corms. Rotting was not observed in corms inoculated using PDA alone. Identification of F. proliferatum was confirmed using sequences of the internal transcribed spacer (ITS) of the ribosomal DNA (ITS1 and ITS4 primers) and sequences of the translation elongation factor alpha (TEF-1) gene (EF-1-986 and EF-728 primers). The ITS and TEF-1 sequences were found to share 99.8% and 99.6% nucleotide similarity to previously published sequences of the ITS (HQ113948) and EF (JN092351) regions of F. proliferatum in GenBank, respectively. The ITS sequence of one isolate was assigned GenBank Accession No. JN86006. To our knowledge, this is the first report of the occurrence of F. proliferatum in Oman or in the Arabian Peninsula. References: (1) C. Linfield. Ann. Appl. Biol. 121:175, 1983. (2) P. E. Nelson et al. Fusarium Species: An Illustrated Manual for Identification. Pennsylvania State University Press, USA, 1983.

Predicting the neurodevelopmental outcome in newborns with hypoxic-ischaemic injury.

The prediction of outcome in newborns with hypoxic ischemic encephalopathy (HIE) is a problematic task. Here, the ability of a combination of clinical, heart rate and EEG measures to predict outcome at 2 years is investigated. One hour of EEG and ECG recordings were obtained from newborns 24 hours after birth. Each newborn was reassessed at 24 months to investigate their neurodevelopmental outcome. From the EEG and ECG recordings, a set of 12 features was extracted. To classify each baby's outcome this data, along with clinical information was fed to a support vector machine. On a per patient basis an ROC area of 0.768 was achieved with 73.68% of newborns being assigned the correct outcome. Overall, this system presents a promising step towards the use of multimodal data for the prediction of neurodevelopmental outcome in newborns with HIE.

Heart rate based automatic seizure detection in the newborn.

This work investigates the efficacy of heart rate (HR) based measures for patient-independent, automatic detection of seizures in newborns. Sixty-two time-domain and frequency-domain features were extracted from the neonatal heart rate signal. These features were classified using a sophisticated support vector machine (SVM) scheme. The performance was evaluated on a large dataset of 208 h from 14 newborn infants. It was shown that the HR can be useful for the detection of neonatal seizures for certain patients yielding an area under the receiver operating characteristic (ROC) curve of up to 82%. On evaluating the system using multiple patients an average ROC area of 0.59 with sensitivity of 60% and specificity of 60%, were obtained. Feature selection was performed and in the majority of patients the performance was degraded. Further analysis of the feature weights found significant variability in feature ranking across all patients. Overall, the patient-independent system presented here was seen to perform well in some patients (2 out of 14) but performed poorly when tested on the entire group.

Heart rate variability during sleep in healthy term newborns in the early postnatal period.

Normative time- and frequency-domain heart rate variability (HRV) measures were extracted during quiet sleep (QS) and active sleep (AS) periods in 30 healthy babies. All newborn infants studied were less than 12 h old and the sleep state was classified using multi-channel video EEG. Three bands were extracted from the heart rate (HR) spectrum: very low frequency (VLF), 0.01-0.04 Hz; low frequency (LF), 0.04-0.2 Hz, and high frequency (HF), >0.2 Hz. All metrics were averaged across all patients and per sleep state to produce a table of normative values. A noticeable peak corresponding to activity in the RSA band was found in 80% patients during QS and 0% of patients during AS, although some broadband activity was observed. The majority of HRV metrics showed a statistically significant separation between QS and AS. It can be concluded that (i) activity in the RSA band is present during QS in the healthy newborn, in the first 12 h of life, (ii) HRV measures are affected by sleep state and (iii) the averaged HRV metrics reported here could assist the interpretation of HRV data from newborns with neonatal illnesses.

Characterisation of heart rate changes and their correlation with EEG during neonatal seizures.

The effect of seizures on instantaneous HR (iHR) in 12 neonates is investigated here. HR can be readily extracted from the ECG and can be employed as an additional signal in seizure detection algorithms. The change in instantaneous HR and its correlation with the change in RMS EEG amplitude were examined. Two methods were employed to classify significant iHR changes. Significant correlation (p 0.05) during seizure was observed in 100% of patients (83.33% of seizures). Overall, significant iHR changes (classified by either method) were found in 83% of patients (50% of seizures). It was found that a markedly higher iHR was observed in patients whose seizures were not classified as having significant iHR changes.

The effect of frequency band on quantitative EEG measures in neonates with hypoxic-ischaemic encephalopathy.

The effect of frequency ranges on three quantitative EEG measures as related to neurodevelopmental outcome at 12-24 months is reported here. Thirteen EEG records from term neonates with moderate hypoxic-ischaemic encephalopathy (HIE) were analyzed. The spectral entropy, spectral edge frequency and relative power were calculated for each EEG channel. 4 separate frequency ranges were employed and their respective variations examined. Graphical and statistical analysis was carried out on the results. Statistical separation between the mean distributions of SEF, H(s) and RP was not observed. The optimal frequency band is dependent on the qEEG measure in question.

Analysing the relationship between voter turnout and health in Ireland.

Health issues are an integral part of the political agenda in Ireland. Yet no study to date has examined the impact of health concerns on political outcomes. This study investigates the relationship between health, both physical and psychological, and perceptions of the health service, and voter turnout in Ireland using the European Social Survey in 2005, (n = 2286, RR 59.7%). The results show that individuals with poor subjective health are significantly less likely to vote in a General Election. Dissatisfaction with the health service is also associated with a lower probability of voting. However these effects interact: those with poor health and who are dissatisfied with the health service are more likely to vote. Psychological well-being has no effect on voter turnout. The health effects identified in this study are large and further work is needed in this area to identify the causal mechanisms underlying this relationship.

Collaborative investigation of an outbreak of Salmonella enterica serotype Newport in England and Wales in 2001 associated with ready-to-eat salad vegetables.

In June 2001, as part of a microbiological study of bagged, ready-to-eat salad products, Salmonella enterica serotype Newport was isolated from a sample of pre-packed green salad distributed by a major supermarket retailer. The strain was characterised by phage typing, plasmid profile typing and pulsed-field gel electrophoresis. Other isolates of S. Newport from cases of human infection in England and Wales in the first six months of 2001 were similarly characterised. Of 60 strains from cases of human infection, 19 were found to be indistinguishable from that isolated from the salad product. This study highlights the benefits of an integrated approach to outbreak investigations, involving the various elements of the PHLS and the Food Standards Agency, and acknowledges the full co-operation of the retailer in ensuring the rapid withdrawal of the contaminated product.

RNA polymerase II in Cajal bodies of amphibian oocytes.

Cajal bodies (coiled bodies) are nuclear organelles that contain a variety of components required for transcription and processing of RNA. Cajal bodies in amphibian oocytes are stained by mAb H14, which recognizes the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II when the heptapeptide repeat is phosphorylated on serine-5. Oocytes were treated with the transcription inhibitor 5, 6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRB), which prevents phosphorylation of the CTD. Cajal bodies from oocytes that had been treated for 2-3 h with DRB no longer stained with mAb H14, but staining reappeared when the inhibitor was washed out. Epitope-tagged transcripts of two small subunits of polymerase II, RPB6 and RPB9, were injected into the cytoplasm of Xenopus and Triturus oocytes. Newly translated RPB6 and RPB9 were specifically targeted to Cajal bodies within 4 h, and Cajal bodies remained the site of highest concentration of tagged protein during the next 2 days. These data suggest that polymerase subunits pass through the Cajal bodies with a transit time no greater than a few hours. We discuss the possibility that Cajal bodies are sites of assembly or modification of the transcription machinery of the nucleus.