Feasibility of simultaneous intracranial EEG-fMRI in humans: a safety study

In epilepsy patients who have electrodes implanted in their brains as part of their pre-surgical assessment, simultaneous intracranial EEG and fMRI (icEEG-fMRI) may provide important localising information and improve understanding of the underlying neuropathology. However, patient safety during icEEG-fMRI has not been addressed. Here the potential health hazards associated with icEEG-fMRI were evaluated theoretically and the main risks identified as: mechanical forces on electrodes from transient magnetic effects, tissue heating due to interaction with the pulsed RF fields and tissue stimulation due to interactions with the switched magnetic gradient fields. These potential hazards were examined experimentally in vitro on a Siemens 3 T Trio, 1.5 T Avanto and a GE 3 T Signa Excite scanner using a Brain Products MR compatible EEG system. No electrode flexion was observed. Temperature measurements demonstrated that heating well above guideline limits can occur. However heating could be kept within safe limits (< 1.0 °C) by using a head transmit RF coil, ensuring EEG cable placement to exit the RF coil along its central z-axis, using specific EEG cable lengths and limiting MRI sequence specific absorption rates (SARs). We found that the risk of tissue damage due to RF-induced heating is low provided implant and scanner specific SAR limits are observed with a safety margin used to account for uncertainties (e.g. in scanner-reported SAR). The observed scanner gradient switching induced current (0.08 mA) and charge density (0.2 μC/cm2) were well within safety limits (0.5 mA and 30 μC/cm2, respectively). Site-specific testing and a conservative approach to safety are required to avoid the risk of adverse events

Bioresponsive hydrogels

We highlight recent developments in hydrogel materials with biological responsiveness built in. These ‘smart’ biomaterials change properties in response to selective biological recognition events. When exposed to a biological target (nutrient, growth factor, receptor, antibody, enzyme, or whole cell), molecular recognition events trigger changes in molecular interactions that translate into macroscopic responses, such as swelling/collapse or solution-to-gel transitions. The hydrogel transitions may be used directly as optical readouts for biosensing, linked to the release of actives for drug delivery, or instigate biochemical signaling events that control or direct cellular behavior. Accordingly, bioresponsive hydrogels have gained significant interest for application in diagnostics, drug delivery, and tissue regeneration/wound healing

Theorising Disability: Beyond Common Sense

This article seeks to introduce the topic of disability to political theory via a discussion of some of the literature produced by disability theorists. The author argues that these more radical approaches conceptualise disability in ways that conflict with ‘common-sense’ notions of disability that tend to underpin political theoretical considerations of the topic. Furthermore, the author suggests that these more radical conceptualisations have profound implications for current debates on social justice, equality and citizenship that highlight the extent to which these notions are also currently underpinned by ‘common-sense’ notions of ‘normality’

Development of a patient reported outcome measure for fatigue in motor neurone disease: the Neurological Fatigue Index (NFI-MND).

BACKGROUND: The objective of this research was to develop a disease-specific measure for fatigue in patients with motor neurone disease (MND) by generating data that would fit the Rasch measurement model. Fatigue was defined as reversible motor weakness and whole-body tiredness that was predominantly brought on by muscular exertion and was partially relieved by rest. METHODS: Qualitative interviews were undertaken to confirm the suitability of a previously identified set of 52 neurological fatigue items as relevant to patients with MND. Patients were recruited from five U.K. MND clinics. Questionnaires were administered during clinic or by post. A sub-sample of patients completed the questionnaire again after 2-4 weeks to assess test-retest validity. Exploratory factor analyses and Rasch analysis were conducted on the item set. RESULTS: Qualitative interviews with ten MND patients confirmed the suitability of 52 previously identified neurological fatigue items as relevant to patients with MND. 298 patients consented to completing the initial questionnaire including this item set, with an additional 78 patients completing the questionnaire a second time after 4-6 weeks. Exploratory Factor Analysis identified five potential subscales that could be conceptualised as representing: 'Energy', 'Reversible muscular weakness' (shortened to 'Weakness'), 'Concentration', 'Effects of heat' and 'Rest'. Of the original five factors, two factors 'Energy' and 'Weakness' met the expectations of the Rasch model. A higher order fatigue summary scale, consisting of items from the 'Energy' and 'Weakness' subscales, was found to fit the Rasch model and have acceptable unidimensionality. The two scales and the higher order summary scale were shown to fulfil model expectations, including assumptions of unidimensionality, local independency and an absence of differential item functioning. CONCLUSIONS: The Neurological Fatigue Index for MND (NFI-MND) is a simple, easy-to-administer fatigue scale. It consists of an 8-item fatigue summary scale in addition to separate scales for measuring fatigue experienced as reversible muscular weakness and fatigue expressed as feelings of low energy and whole body tiredness. The underlying two factor structure supports the patient concept of fatigue derived from qualitative interviews in this population. All three scales were shown to be reliable and capable of interval level measurement

Determining the temporal profile of intracranial pressure changes following transient stroke in an ovine model

Cerebral edema and elevated intracranial pressure (ICP) are the leading cause of death in the first week following stroke. Despite this, current treatments are limited and fail to address the underlying mechanisms of swelling, highlighting the need for targeted treatments. When screening promising novel agents, it is essential to use clinically relevant large animal models to increase the likelihood of successful clinical translation. As such, we sought to develop a survival model of transient middle cerebral artery occlusion (tMCAO) in the sheep and subsequently characterize the temporal profile of cerebral edema and elevated ICP following stroke in this novel, clinically relevant model. Merino-sheep (27M;31F) were anesthetized and subject to 2 h tMCAO with reperfusion or sham surgery. Following surgery, animals were allowed to recover and returned to their home pens. At preselected times points ranging from 1 to 7 days post-stroke, animals were re-anesthetized, ICP measured for 4 h, followed by imaging with MRI to determine cerebral edema, midline shift and infarct volume (FLAIR, T2 and DWI). Animals were subsequently euthanized and their brain removed for immunohistochemical analysis. Serum and cerebrospinal fluid samples were also collected and analyzed for substance P (SP) using ELISA. Intracranial pressure and MRI scans were normal in sham animals. Following stroke, ICP rose gradually over time and by 5 days was significantly (p < 0.0001) elevated above sham levels. Profound cerebral edema was observed as early as 2 days post-stroke and continued to evolve out to 6 days, resulting in significant midline shift which was most prominent at 5 days post-stroke (p < 0.01), in keeping with increasing ICP. Serum SP levels were significantly elevated (p < 0.01) by 7 days post-tMCAO. We have successfully developed a survival model of ovine tMCAO and characterized the temporal profile of ICP. Peak ICP elevation, cerebral edema and midline shift occurred at days 5-6 following stroke, accompanied by an elevation in serum SP. Our findings suggest that novel therapeutic agents screened in this model targeting cerebral edema and elevated ICP would most likely be effective when administered prior to 5 days, or as early as possible following stroke onset.Annabel J. Sorby-Adams, Anna V. Leonard, Levi E. Elms, Oana C. Marian, Jan W. Hoving, Nawaf Yassi, Robert Vink, Emma Thornton and Renée J. Turne

Search for VHE gamma rays from SS433/W50 with the CANGAROO-II telescope

SS433, located at the center of the supernova remnant W50, is a close proximity binary system consisting of a compact star and a normal star. Jets of material are directed outwards from the vicinity of the compact star symmetrically to the east and west. Non-thermal hard X-ray emission is detected from lobes lying on both sides. Shock accelerated electrons are expected to generate sub-TeV gamma rays through the inverse-Compton process in the lobes. Observations of the western X-ray lobe region of SS433/W50 system have been performed to detect sub-TeV gamma-rays using the 10m CANGAROO-II telescope in August and September, 2001, and July and September, 2002. The total observation times are 85.2 hours for ON source, and 80.8 hours for OFF source data. No significant excess of sub-TeV gamma rays has been found at 3 regions of the western X-ray lobe of SS433/W50 system. We have derived 99% confidence level upper limits to the fluxes of gamma rays and have set constraints on the strengths of the magnetic fields assuming the synchrotron/inverse-Compton model for the wide energy range of photon spectrum from radio to TeV. The derived lower limits are 4.3 microgauss for the center of the brightest X-ray emission region and 6.3 microgauss for the far end from SS433 in the western X-ray lobe. In addition, we suggest that the spot-like X-ray emission may provide a major contribution to the hardest X-ray spectrum in the lobe.Comment: 7 pages, 8 figures, to be published in Astroparticle Physic

Organic nitrate aerosol formation via NO³ + biogenic volatile organic compounds in the southeastern United States

Gas- and aerosol-phase measurements of oxidants, biogenic volatile organic compounds (BVOCs) and organic nitrates made during the Southern Oxidant and Aerosol Study (SOAS campaign, Summer 2013) in central Alabama show that a nitrate radical (NO₃) reaction with monoterpenes leads to significant secondary aerosol formation. Cumulative losses of NO₃ to terpenes are correlated with increase in gasand aerosol-organic nitrate concentrations made during the campaign. Correlation of NO₃ radical consumption to organic nitrate aerosol formation as measured by aerosol mass spectrometry and thermal dissociation laser-induced fluorescence suggests a molar yield of aerosol-phase monoterpene nitrates of 23–44 %. Compounds observed via chemical ionization mass spectrometry (CIMS) are correlated to predicted nitrate loss to BVOCs and show C₁₀H₁₇NO₅, likely a hydroperoxy nitrate, is a major nitrate-oxidized terpene product being incorporated into aerosols. The comparable isoprene product C₅H₉NO₅ was observed to contribute less than 1% of the total organic nitrate in the aerosol phase and correlations show that it is principally a gas-phase product from nitrate oxidation of isoprene. Organic nitrates comprise between 30 and 45% of the NOy budget during SOAS. Inorganic nitrates were also monitored and showed that during incidents of increased coarse-mode mineral dust, HNO₃ uptake produced nitrate aerosol mass loading at a rate comparable to that of organic nitrate produced via NO₃ CBVOCs

Mitral regurgitation quantification by cardiac magnetic resonance imaging (MRI) remains reproducible between software solutions [version 3; peer review: 2 approved]

Background: The reproducibility of mitral regurgitation (MR) quantification by cardiovascular magnetic resonance (CMR) imaging using different software solutions remains unclear. This research aimed to investigate the reproducibility of MR quantification between two software solutions: MASS (version 2019 EXP, LUMC, Netherlands) and CAAS (version 5.2, Pie Medical Imaging). Methods: CMR data of 35 patients with MR (12 primary MR, 13 mitral valve repair/replacement, and ten secondary MR) was used. Four methods of MR volume quantification were studied, including two 4D-flow CMR methods (MRMVAV and MRJet) and two non-4D-flow techniques (MRStandard and MRLVRV). We conducted within-software and inter-software correlation and agreement analyses. Results: All methods demonstrated significant correlation between the two software solutions: MRStandard (r=0.92, p<0.001), MRLVRV (r=0.95, p<0.001), MRJet (r=0.86, p<0.001), and MRMVAV (r=0.91, p<0.001). Between CAAS and MASS, MRJet and MRMVAV, compared to each of the four methods, were the only methods not to be associated with significant bias. Conclusions: We conclude that 4D-flow CMR methods demonstrate equivalent reproducibility to non-4D-flow methods but greater levels of agreement between software solutions