Functional network topology in drug resistant and well-controlled idiopathic generalized epilepsy:a resting state functional MRI study

Despite an increasing number of drug treatment options for people with idiopathic generalized epilepsy (IGE), drug resistance remains a significant issue and the mechanisms underlying it remain poorly understood. Previous studies have largely focused on potential cellular or genetic explanations for drug resistance. However, epilepsy is understood to be a network disorder and there is a growing body of literature suggesting altered topology of large-scale resting networks in people with epilepsy compared with controls. We hypothesize that network alterations may also play a role in seizure control. The aim of this study was to compare resting state functional network structure between well-controlled IGE (WC-IGE), drug resistant IGE (DR-IGE) and healthy controls. Thirty-three participants with IGE (10 with WC-IGE and 23 with DR-IGE) and 34 controls were included. Resting state functional MRI networks were constructed using the Functional Connectivity Toolbox (CONN). Global graph theoretic network measures of average node strength (an equivalent measure to mean degree in a network that is fully connected), node strength distribution variance, characteristic path length, average clustering coefficient, small-world index and average betweenness centrality were computed. Graphs were constructed separately for positively weighted connections and for absolute values. Individual nodal values of strength and betweenness centrality were also measured and 'hub nodes' were compared between groups. Outcome measures were assessed across the three groups and between both groups with IGE and controls. The IGE group as a whole had a higher average node strength, characteristic path length and average betweenness centrality. There were no clear differences between groups according to seizure control. Outcome metrics were sensitive to whether negatively correlated connections were included in network construction. There were no clear differences in the location of 'hub nodes' between groups. The results suggest that, irrespective of seizure control, IGE interictal network topology is more regular and has a higher global connectivity compared to controls, with no alteration in hub node locations. These alterations may produce a resting state network that is more vulnerable to transitioning to the seizure state. It is possible that the lack of apparent influence of seizure control on network topology is limited by challenges in classifying drug response. It is also demonstrated that network topological features are influenced by the sign of connectivity weights and therefore future methodological work is warranted to account for anticorrelations in graph theoretic studies

The RAPID-CTCA trial (Rapid Assessment of Potential Ischaemic Heart Disease with CTCA) - a multicentre parallel-group randomised trial to compare early computerised tomography coronary angiography versus standard care in patients presenting with suspected or confirmed acute coronary syndrome: study protocol for a randomised controlled trial.

BACKGROUND: Emergency department attendances with chest pain requiring assessment for acute coronary syndrome (ACS) are a major global health issue. Standard assessment includes history, examination, electrocardiogram (ECG) and serial troponin testing. Computerised tomography coronary angiography (CTCA) enables additional anatomical assessment of patients for coronary artery disease (CAD) but has only been studied in very low-risk patients. This trial aims to investigate the effect of early CTCA upon interventions, event rates and health care costs in patients with suspected/confirmed ACS who are at intermediate risk. METHODS/DESIGN: Participants will be recruited in about 35 tertiary and district general hospitals in the UK. Patients ≥18 years old with symptoms with suspected/confirmed ACS with at least one of the following will be included: (1) ECG abnormalities, e.g. ST-segment depression >0.5 mm; (2) history of ischaemic heart disease; (3) troponin elevation above the 99(th) centile of the normal reference range or increase in high-sensitivity troponin meeting European Society of Cardiology criteria for 'rule-in' of myocardial infarction (MI). The early use of ≥64-slice CTCA as part of routine assessment will be compared to standard care. The primary endpoint will be 1-year all-cause death or recurrent type 1 or type 4b MI at 1 year, measured as the time to such event. A number of secondary clinical, process and safety endpoints will be collected and analysed. Cost effectiveness will be estimated in terms of the lifetime incremental cost per quality-adjusted life year gained. We plan to recruit 2424 (2500 with ~3% drop-out) evaluable patients (1212 per arm) to have 90% power to detect a 20% versus 15% difference in 1-year death or recurrent type 1 MI or type 4b MI, two-sided p < 0.05. Analysis will be on an intention-to-treat basis. The relationship between intervention and the primary outcome will be analysed using Cox proportional hazard regression adjusted for study site (used to stratify the randomisation), age, baseline Global Registry of Acute Coronary Events score, previous CAD and baseline troponin level. The results will be expressed as a hazard ratio with the corresponding 95% confidence intervals and p value. DISCUSSION: The Rapid Assessment of Potential Ischaemic Heart Disease with CTCA (RAPID-CTCA) trial will recruit 2500 participants across about 35 hospital sites. It will be the first study to investigate the role of CTCA in the early assessment of patients with suspected or confirmed ACS who are at intermediate risk and including patients who have raised troponin measurements during initial assessment. TRIAL REGISTRATION: ISRCTN19102565 . Registered on 3 October 2014. ClinicalTrials.gov: NCT02284191

Synaptic and transcriptionally downregulated genes are associated with cortical thickness differences in autism.

Differences in cortical morphology-in particular, cortical volume, thickness and surface area-have been reported in individuals with autism. However, it is unclear what aspects of genetic and transcriptomic variation are associated with these differences. Here we investigate the genetic correlates of global cortical thickness differences (ΔCT) in children with autism. We used Partial Least Squares Regression (PLSR) on structural MRI data from 548 children (166 with autism, 295 neurotypical children and 87 children with ADHD) and cortical gene expression data from the Allen Institute for Brain Science to identify genetic correlates of ΔCT in autism. We identify that these genes are enriched for synaptic transmission pathways and explain significant variation in ΔCT. These genes are also significantly enriched for genes dysregulated in the autism post-mortem cortex (Odd Ratio (OR) = 1.11, Pcorrected  10-14), driven entirely by downregulated genes (OR = 1.87, Pcorrected  10-15). We validated the enrichment for downregulated genes in two independent data sets: Validation 1 (OR = 1.44, Pcorrected = 0.004) and Validation 2 (OR = 1.30; Pcorrected = 0.001). We conclude that transcriptionally downregulated genes implicated in autism are robustly associated with global changes in cortical thickness variability in children with autism

Learners and their workplaces: towards a strategic model of flexible delivery of training in the workplace

Although the flexible delivery of training in the workplace has become a favoured policy position for training authorities in both Britain and Australia, this article reviews research that indicates neither learners nor their workplaces are well prepared. Drawing on the author\u27s own research and that from the broader literature, the article develops a model for the preparation of learners and workplaces for flexible delivery of training. Deriving from the proposed model, the article suggests a wide range of strategies that may be used in preparing learners and workplaces for successful engagement with the flexible delivery of training. <br /

The effect of ginger (Zingiber officinale) on platelet aggregation: A systematic literature review

10.1371/journal.pone.0141119PLoS ONE1010e014111

Erratum: The effect of ginger (zingiber officinale) on platelet aggregation: A systematic literature review (PLoS ONE (2015) 10:10 (e0141119))

10.1371/journal.pone.0143675PLoS ONE1011e014367

Relating diffusion tensor imaging measurements to microstructural quantities in the cerebral cortex in multiple sclerosis

To investigate whether the observed anisotropic diffusion in cerebral cortex may reflect its columnar cytoarchitecture and myeloarchitecture, as a potential biomarker for disease-related changes, we compared postmortem diffusion magnetic resonance imaging scans of nine multiple sclerosis brains with histology measures from the same regions. Histology measurements assessed the cortical minicolumnar structure based on cell bodies and associated axon bundles in dorsolateral prefrontal cortex (Area 9), Heschl's gyrus (Area 41), and primary visual cortex (V1). Diffusivity measures included mean diffusivity, fractional anisotropy of the cortex, and three specific measures that may relate to the radial minicolumn structure: the angle of the principal diffusion direction in the cortex, the component that was perpendicular to the radial direction, and the component that was parallel to the radial direction. The cellular minicolumn microcircuit features were correlated with diffusion angle in Areas 9 and 41, and the axon bundle features were correlated with angle in Area 9 and to the parallel component in V1 cortex. This may reflect the effect of minicolumn microcircuit organisation on diffusion in the cortex, due to the number of coherently arranged membranes and myelinated structures. Several of the cortical diffusion measures showed group differences between MS brains and control brains. Differences between brain regions were also found in histology and diffusivity measurements consistent with established regional variation in cytoarchitecture and myeloarchitecture. Therefore, these novel measures may provide a surrogate of cortical organisation as a potential biomarker, which is particularly relevant for detecting regional changes in neurological disorders

Amorphous carbon interlayers for gold on elastomer stretchable conductors

NoGold on polydimethylsiloxane (PDMS) stretchable conductors were prepared using a novel approach by interlacing an hydrogenated amorphous carbon (a-C : H) layer between the deposited metal layer and the elastomer. AFM analysis of the a-C : H film surface before gold deposition shows nanoscale buckling, the corresponding increase in specific surface area corresponds to a strain compensation for the first 4–6% of bi-axial tensile loading. Without this interlayer, the deposited gold films show much smaller and uni-directional ripples as well as more cracks and delaminations. With a-C : H interlayer, the initial electrical resistivity of the metal film decreases markedly (280-fold decrease to 8 × 10−6 Ω cm). This is not due to conduction within the carbon interlayer; both a-C : H/PDMS and PDMS substrates are electrically insulating. Upon cyclic tensile loading, both films become more resistive, but return to their initial state after 20 tensile cycles up to 60% strain. Profiling experiments using secondary ion mass spectroscopy and x-ray photoelectron spectroscopy indicate that the a-C : H layer intermixes with the PDMS, resulting in a graded layer of decreasing stiffness. We believe that both this graded layer and the surface buckling contribute to the observed improvement in the electrical performance of these stretchable conductors

Aortopexy for the treatment of tracheobronchomalacia in 100 children: a 10-year single-centre experience

OBJECTIVES Our study describes and analyses the results from aortopexy for the treatment of airway malacia in children. METHODS Demographic data, characteristics and preoperative, operative and outcome details, including the need for reintervention, were collected for children undergoing aortopexy between 2006 and 2016. RESULTS One hundred patients [median age 8.2 months, interquartile range (IQR) 3.3-26.0 months] underwent aortopexy. Sixty-four (64%) patients had tracheomalacia (TM) only, 24 (24%) patients had TM extending into their bronchus (tracheobronchomalacia) and 11 (11%) patients had bronchomalacia. Forty-one (41%) children had gastro-oesophageal reflux disease, of which 17 (41%) children underwent a Nissen fundoplication. Twenty-eight (28%) children underwent a tracheo-oesophageal fistula repair prior to aortopexy (median 5.7 months, IQR 2.9-17.6 months). The median duration of follow-up was 5.3 years (IQR 2.9-7.5 years). Thirty-five (35%) patients were on mechanical ventilatory support before aortopexy. Twenty-seven (77%) patients could be safely weaned from ventilator support during the same admission after aortopexy (median 2 days, IQR 0-3 days). Fourteen patients required reintervention. Overall mortality was 16%. Multivariable analysis revealed preoperative ventilation (P = 0.004) and bronchial involvement (P = 0.004) to be adverse predictors of survival. Only bronchial involvement was a predictor for reintervention (P = 0.012). CONCLUSIONS Aortopexy appears to be an effective procedure in the treatment of children with severe airway malacia. Bronchial involvement is associated with adverse outcome, and other procedures could be more suitable. For the treatment of severe airway malacia with isolated airway compression, we currently recommend aortopexy to be considered