Background EEG connectivity captures the time-course of epileptogenesis in a mouse model of epilepsy

This is the author accepted manuscript. The final version is available from Society for Neuroscience via the DOI in this recordLarge-scale brain networks are increasingly recognized as important for the generation of seizures in epilepsy. However, how a network evolves from a healthy state through the process of epileptogenesis remains unclear. To address this question, here, we study longitudinal epicranial background EEG recordings (30 electrodes, EEG free from epileptiform activity) of a mouse model of mesial temporal lobe epilepsy. We analyse functional connectivity networks and observe that over the time-course of epileptogenesis the networks become increasingly asymmetric. Furthermore, computational modelling reveals that a set of nodes, located outside of the region of initial insult, emerges as particularly important for the network dynamics. These findings are consistent with experimental observations, thus demonstrating that ictogenic mechanisms can be revealed on the EEG, that computational models can be used to monitor unfolding epileptogenesis and that both the primary focus and epileptic network play a role in epileptogenesis.Epilepsy Research UKEngineering and Physical Sciences Research Council (EPSRC)Wellcome Trus

Interpreting and acting upon home blood pressure readings: A qualitative study

This article is made available through the Brunel Open Access Publishing Fund. Copyright @ 2013 Vasileiou et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Recent guidelines recognize the importance of home blood pressure monitoring (HBPM) as an adjunct to clinical measurements. We explored how people who have purchased and use a home blood pressure (BP) monitor make sense of, and act upon, readings and how they communicate with their doctor about the practice of home monitoring. Methods: A qualitative study was designed and participants were purposively recruited from several areas in England, UK. Semi-structured in-depth interviews were conducted with 18 users of home BP monitors. The transcribed data were thematically analysed. Results: Interpretation of home BP readings is complex, and is often characterised by uncertainty. People seek to assess value normality using ‘rules of thumb’, and often aim to identify the potential causes of the readings. This is done by drawing on lay models of BP function and by contextualising the readings to personal circumstances. Based on the perceived causes of the problematic readings, actions are initiated, mostly relating to changes in daily routines. Contacting the doctor was more likely when the problematic readings persisted and could not be easily explained, or when participants did not succeed in regulating their BP through their other interventions. Most users had notified their doctor of the practice of home monitoring, but medical involvement varied, with some participants reporting disinterest or reservations by doctors. Conclusions: Involvement from doctors can help people overcome difficulties and resolve uncertainties around the interpretation of home readings, and ensure that the rules of thumb are appropriate. Home monitoring can be used to strengthen the patient-clinician relationship

Mass extinctions and supernova explosions

A nearby supernova (SN) explosion could have negatively influenced life on Earth, maybe even been responsible for mass extinctions. Mass extinction poses a significant extinction of numerous species on Earth, as recorded in the paleontologic, paleoclimatic, and geological record of our planet. Depending on the distance between the Sun and the SN, different types of threats have to be considered, such as ozone depletion on Earth, causing increased exposure to the Sun's ultraviolet radiation, or the direct exposure of lethal x-rays. Another indirect effect is cloud formation, induced by cosmic rays in the atmosphere which result in a drop in the Earth's temperature, causing major glaciations of the Earth. The discovery of highly intensive gamma ray bursts (GRBs), which could be connected to SNe, initiated further discussions on possible life-threatening events in Earth's history. The probability that GRBs hit the Earth is very low. Nevertheless, a past interaction of Earth with GRBs and/or SNe cannot be excluded and might even have been responsible for past extinction events.Comment: Chapter for forthcoming book: Handbook of Supernovae, P. Murdin and A. Alsabeti (eds.), Springer International Publishing (in press

Increasing dominance of large lianas in Amazonian forests

Ecological orthodoxy suggests that old-growth forests should be close to dynamic equilibrium, but this view has been challenged by recent findings that neotropical forests are accumulating carbon and biomass, possibly in response to the increasing atmospheric concentrations of carbon dioxide. However, it is unclear whether the recent increase in tree biomass has been accompanied by a shift in community composition. Such changes could reduce or enhance the carbon storage potential of old-growth forests in the long term. Here we show that non-fragmented Amazon forests are experiencing a concerted increase in the density, basal area and mean size of woody climbing plants (lianas). Over the last two decades of the twentieth century the dominance of large lianas relative to trees has increased by 1.7–4.6% a year. Lianas enhance tree mortality and suppress tree growth, so their rapid increase implies that the tropical terrestrial carbon sink may shut down sooner than current models suggest. Predictions of future tropical carbon fluxes will need to account for the changing composition and dynamics of supposedly undisturbed forests

Arterial oxygen content is precisely maintained by graded erythrocytotic responses in settings of high/normal serum iron levels, and predicts exercise capacity: an observational study of hypoxaemic patients with pulmonary arteriovenous malformations.

Oxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity.165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100.There was wide variation in SaO2 on air (78.5-99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up.Haemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses

Routes for breaching and protecting genetic privacy

We are entering the era of ubiquitous genetic information for research, clinical care, and personal curiosity. Sharing these datasets is vital for rapid progress in understanding the genetic basis of human diseases. However, one growing concern is the ability to protect the genetic privacy of the data originators. Here, we technically map threats to genetic privacy and discuss potential mitigation strategies for privacy-preserving dissemination of genetic data.Comment: Draft for comment

Image-Derived Input Function for Human Brain Using High Resolution PET Imaging with [11C](R)-rolipram and [11C]PBR28

The aim of this study was to test seven previously published image-input methods in state-of-the-art high resolution PET brain images. Images were obtained with a High Resolution Research Tomograph plus a resolution-recovery reconstruction algorithm using two different radioligands with different radiometabolite fractions. Three of the methods required arterial blood samples to scale the image-input, and four were blood-free methods. values was quantified using a scoring system. Using the image input methods that gave the most accurate results with Logan analysis, we also performed kinetic modelling with a two-tissue compartment model.)-rolipram, which has a lower metabolite fraction. Compartment modeling gave less reliable results, especially for the estimation of individual rate constants.C]PBR28), the more difficult it is to obtain a reliable image-derived input function; and 4) in association with image inputs, graphical analyses should be preferred over compartmental modelling

Accuracy of advanced versus strictly conventional 12-lead ECG for detection and screening of coronary artery disease, left ventricular hypertrophy and left ventricular systolic dysfunction

<p>Abstract</p> <p>Background</p> <p>Resting conventional 12-lead ECG has low sensitivity for detection of coronary artery disease (CAD) and left ventricular hypertrophy (LVH) and low positive predictive value (PPV) for prediction of left ventricular systolic dysfunction (LVSD). We hypothesized that a ~5-min resting 12-lead <it>advanced </it>ECG test ("A-ECG") that combined results from both the advanced and conventional ECG could more accurately screen for these conditions than strictly conventional ECG.</p> <p>Methods</p> <p>Results from nearly every conventional and advanced resting ECG parameter known from the literature to have diagnostic or predictive value were first retrospectively evaluated in 418 healthy controls and 290 patients with imaging-proven CAD, LVH and/or LVSD. Each ECG parameter was examined for potential inclusion within multi-parameter A-ECG scores derived from multivariate regression models that were designed to optimally screen for disease in general or LVSD in particular. The performance of the best retrospectively-validated A-ECG scores was then compared against that of optimized pooled criteria from the strictly conventional ECG in a test set of 315 additional individuals.</p> <p>Results</p> <p>Compared to optimized pooled criteria from the strictly conventional ECG, a 7-parameter A-ECG score validated in the training set increased the sensitivity of resting ECG for identifying disease in the test set from 78% (72-84%) to 92% (88-96%) (P < 0.0001) while also increasing specificity from 85% (77-91%) to 94% (88-98%) (P < 0.05). In diseased patients, another 5-parameter A-ECG score increased the PPV of ECG for LVSD from 53% (41-65%) to 92% (78-98%) (P < 0.0001) without compromising related negative predictive value.</p> <p>Conclusion</p> <p>Resting 12-lead A-ECG scoring is more accurate than strictly conventional ECG in screening for CAD, LVH and LVSD.</p