Post-eruptive volcano inflation following major magma drainage: Interplay between models of viscoelastic response influence and models of magma inflow at Bárðarbunga caldera, Iceland, 2015-2018

&amp;lt;p&amp;gt;Unrest at B&amp;amp;#225;r&amp;amp;#240;arbunga after a caldera collapse in 2014-2015 includes elevated seismicity beginning about six months after the eruption ended, including nine Mw&amp;gt;4.5 earthquakes. The earthquakes occurred mostly on the northern and southern parts of a caldera ring fault. Global Navigation Satellite System (GNSS, in particular, Global Positioning System; GPS) and Interferometric Synthetic Aperture Radar (InSAR) geodesy are applied to evaluate the spatial and temporal pattern of ground deformation around B&amp;amp;#225;r&amp;amp;#240;arbunga caldera outside the icecap, in 2015-2018, when deformation rates were relatively steady. The aim is to study the role of viscoelastic relaxation following major magma drainage versus renewed magma inflow as an explanation for the ongoing unrest.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;The largest horizontal velocity is measured at GPS station KISA (3 km from caldera rim), 141 mm/yr in direction N47&amp;lt;sup&amp;gt;o&amp;lt;/sup&amp;gt;E relative to the Eurasian plate in 2015-2018. GPS and InSAR observations show that the velocities decay rapidly outward from the caldera. We correct our observations for Glacial Isostatic Adjustment and plate spreading to extract the deformation related to volcanic activity. After this correction, some GPS sites show subsidence.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;We use a reference Earth model to initially evaluate the contribution of viscoelastic processes to the observed deformation field. We model the deformation within a half-space composed of a 7-km thick elastic layer on top of a viscoelastic layer with a viscosity of 5 x 10&amp;lt;sup&amp;gt;18&amp;lt;/sup&amp;gt; Pa s, considering two co-eruptive contributors to the viscoelastic relaxation: &amp;amp;#8220;non-piston&amp;amp;#8221; magma withdrawal at 10 km depth (modelled as pressure drop in a spherical source) and caldera collapse (modelled as surface unloading). The other model we test is the magma inflow in an elastic half-space. Both the viscoelastic relaxation and magma inflow create horizontal outward movements around the caldera, and uplift at the surface projection of the source center in 2015-2018. Viscoelastic response due to magma withdrawal results in subsidence in the area outside the icecap. Magma inflow creates rapid surface velocity decay as observed.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;We explore further two parameters in the viscoelastic reference model: the viscosity and the &amp;quot;non-piston&amp;quot; magma withdrawal volume. Our comparison between the corrected InSAR velocities and viscoelastic models suggests a viscosity of 2.6&amp;amp;#215;10&amp;lt;sup&amp;gt;18&amp;lt;/sup&amp;gt; Pa s and 0.36 km&amp;lt;sup&amp;gt;3&amp;lt;/sup&amp;gt; of &amp;amp;#8220;non-piston&amp;amp;#8221; magma withdrawal volume, given by the optimal reduced Chi-squared statistic. When the deformation is explained using only magma inflow into a single spherical source (and no viscoelastic response), the optimal model suggests an inflow rate at 1&amp;amp;#215;10&amp;lt;sup&amp;gt;7&amp;lt;/sup&amp;gt; m&amp;lt;sup&amp;gt;3&amp;lt;/sup&amp;gt;/yr at 700 m depth. A magma inflow model with more model parameters is also a possible explanation, including sill inflation at 10 km together with slip on caldera ring faults. Our reference Earth model and the two end-member models suggest that there is a trade-off between the viscoelastic relaxation and the magma inflow, since they produce similar deformation signals outside the icecap. However, to reproduce details of the observed deformation, both processes are required. A viscoelastic-only model cannot fully explain the fast velocity decay away from the caldera, whereas a magma inflow-only model cannot explain the subsidence observed at several locations.&amp;lt;/p&amp;gt; </jats:p

Deformation at Krafla and Bjarnarflag geothermal areas, Northern Volcanic Zone of Iceland, 1993-2015

The Krafla volcanic system has geothermal areas within the Krafla caldera and at Bjarnarflag in the Krafla fissure swarm, 9-km south of the Krafla caldera. Arrays of boreholes extract geothermal fluids for power plants in both areas. We collected and analyzed InSAR, GPS, and leveling data spanning 1993–2015 in order to investigate crustal deformation in these areas. The volcanic zone hosting the geothermal areas is also subject to large scale regional deformation processes, including plate spreading and deflation of the Krafla volcanic system. These deformation processes have to be taken into account in order to isolate the geothermal deformation signal. Plate spreading produces the largest horizontal displacements, but the regional deformation pattern also suggests readjustment of the Krafla system at depth after the 1975–1984 Krafla rifting episode. Observed deformation can be fit by an inflation source at about 20 km depth north of Krafla and a deflation source at similar depth directly below the Krafla caldera. Deflation signal along the fissure swarm can be reproduced by a 1-km wide sill at 4 km depth closing by 2–4 cm per year. These sources are considered to approximate the combined effects of vertical deformation associated with plate spreading and post-rifting response. Local deformation at the geothermal areas is well resolved in addition to these signals. InSAR shows that deformation at Bjarnarflag is elongated along the direction of the Krafla fissure swarm (∼4 km by ∼2 km) while it is circular at Krafla (∼5 km diameter). Rates of deflation at Krafla and Bjarnarflag geothermal areas have been relatively steady. Average volume decrease of about 6.6 ×10⁵ m³/yr for Krafla and 3.9 ×10⁵ m³/yr for Bjanarflag are found at sources located at ∼1.5 km depth, when interpreted by a spherical point source of pressure. This volume change represents about 8 ×10 −3 m³/ton of the mass of geothermal fluid extracted per year, indicating important renewal of the geothermal reservoir by water flow

Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring

Over the last 2 decades, a large number of neurophysiological and neuroimaging studies of patients with schizophrenia have furnished in vivo evidence for dysconnectivity, ie, abnormal functional integration of brain processes. While the evidence for dysconnectivity in schizophrenia is strong, its etiology, pathophysiological mechanisms, and significance for clinical symptoms are unclear. First, dysconnectivity could result from aberrant wiring of connections during development, from aberrant synaptic plasticity, or from both. Second, it is not clear how schizophrenic symptoms can be understood mechanistically as a consequence of dysconnectivity. Third, if dysconnectivity is the primary pathophysiology, and not just an epiphenomenon, then it should provide a mechanistic explanation for known empirical facts about schizophrenia. This article addresses these 3 issues in the framework of the dysconnection hypothesis. This theory postulates that the core pathology in schizophrenia resides in aberrant N-methyl-D-aspartate receptor (NMDAR)–mediated synaptic plasticity due to abnormal regulation of NMDARs by neuromodulatory transmitters like dopamine, serotonin, or acetylcholine. We argue that this neurobiological mechanism can explain failures of self-monitoring, leading to a mechanistic explanation for first-rank symptoms as pathognomonic features of schizophrenia, and may provide a basis for future diagnostic classifications with physiologically defined patient subgroups. Finally, we test the explanatory power of our theory against a list of empirical facts about schizophrenia

Correlation between disability and MRI findings in lumbar spinal stenosis: A prospective study of 109 patients operated on by decompression

Background and purpose MRI is the modality of choice when diagnosing spinal stenosis but it also shows that stenosis is prevalent in asymptomatic subjects over 60. The relationship between preoperative health-related quality of life, functional status, leg and back pain, and the objectively measured dural sac area in single and multilevel stenosis is unknown. We assessed this relationship in a prospective study. Patients and methods The cohort included 109 consecutive patients with central spinal stenosis operated on with decompressive laminectomy or laminotomy. Preoperatively, all patients completed the questionnaires for EQ-5D, SF-36, Oswestry disability index (ODI), estimated walking distance and leg and back pain (VAS). The cross-sectional area of the dural sac was measured at relevant disc levels in mm(2), and spondylolisthesis was measured in mm. For comparison, the area of the most narrow level, the number of levels with dural sac area < 70 mm(2), and spondylolisthesis were studied. Results Before surgery, patients with central spinal stenosis had low HRLQoL and functional status, and high pain levels. Patients with multilevel stenosis had better general health (p = 0.04) and less leg and back pain despite having smaller dural sac area than patients with single-level stenosis. There was a poor correlation between walking distance, ODI, the SF-36, EQ-5D, and leg and back pain levels on the one hand and dural sac area on the other. Women more often had multilevel spinal stenosis (p = 0.05) and spondylolisthesis (p < 0.001). Spondylolisthetic patients more often had small dural sac area (p = 0.04) and multilevel stenosis (p = 0.06). Interpretation Our findings indicate that HRQoL, function, and pain measured preoperatively correlate with morphological changes on MRI to a limited extent

Unexpected large eruptions from buoyant magma bodies within viscoelastic crust

Large volume effusive eruptions with relatively minor observed precursory signals are at odds with widely used models to interpret volcano deformation. Here we propose a new modelling framework that resolves this discrepancy by accounting for magma buoyancy, viscoelastic crustal properties, and sustained magma channels. At low magma accumulation rates, the stability of deep magma bodies is governed by the magma-host rock density contrast and the magma body thickness. During eruptions, inelastic processes including magma mush erosion and thermal effects, can form a sustained channel that supports magma flow, driven by the pressure difference between the magma body and surface vents. At failure onset, it may be difficult to forecast the final eruption volume; pressure in a magma body may drop well below the lithostatic load, create under-pressure and initiate a caldera collapse, despite only modest precursors

Integration of micro-gravity and geodetic data to constrain shallow system mass changes at Krafla Volcano, N Iceland

New and previously published micro-gravity data are combined with InSAR data, precise levelling and GPS measurements to produce a model for the processes operating at Krafla volcano, 20 years after its most recent eruption. The data have been divided into two periods: from 1990 to 1995 and from 1996 to 2003 and show that the rate of deflation at Krafla is decaying exponentially. The net micro-gravity change at the centre of the caldera is shown, using the measured Free Air Gradient, to be -85 μGal for the first and -100 μGal for the second period. After consideration of the effects of water extraction by the geothermal power station within the caldera, the net gravity decreases are -73 ± 17 μGal for the first and -65 ± 17 μGal for the second period. These decreases are interpreted in terms of magma drainage. Following a Mogi point source model we calculate the mass decrease to be ~2 x 1010 kg/yr reflecting a drainage rate of ~0.23 m3/s, similar to the ~0.13 m3/s drainage rate previously found at Askja volcano, N-Iceland. Based on the evidence for deeper magma reservoirs and the similarity between the two volcanic systems, we suggest a pressure-link between Askja and Krafla at deeper levels (at the lower crust or the crust-mantle boundary). After the Krafla fires, co-rifting pressure decrease of a deep source at Krafla stimulated the subsequent inflow of magma, eventually affecting conditions along the plate boundary in N-Iceland, as far away as Askja. We anticipate that the pressure of the deeper reservoir at Krafla will reach a critical value and eventually magma will rise from there to the shallow magma chamber, possibly initiating a new rifting episode. We have demonstrated that by examining micro-gravity and geodetic data, our knowledge of active volcanic systems can be significantly improved

Proinsulin C-peptide elicits disaggregation of insulin resulting in enhanced physiological insulin effects

Using surface plasmon resonance (SPR) and electrospray mass spectrometry (ESI-MS), proinsulin C-peptide was found to influence insulin-insulin interactions. In SPR with chip-bound insulin, C-peptide mixed with analyte insulin increased the binding, while alone C-peptide did not. A control peptide with the same residues in random sequence had little effect. In ESI-MS, C-peptide lowered the presence of insulin hexamer. The data suggest that C-peptide promotes insulin disaggregation. Insulin/insulin oligomer μM dissociation constants were determined. Compatible with these findings, type 1 diabetic patients receiving insulin and C-peptide developed 66% more stimulation of glucose metabolism than when given insulin alone. A role of C-peptide in promoting insulin disaggregation may be important physiologically during exocytosis of pancreatic β-cell secretory granulae and pharmacologically at insulin injection sites. It is compatible with the normal co-release of C-peptide and insulin and may contribute to the beneficial effect of C-peptide and insulin replacement in type 1 diabetics

Exploring the Dynamic Range of the Kinetic Exclusion Assay in Characterizing Antigen-Antibody Interactions

Therapeutic antibodies are often engineered or selected to have high on-target binding affinities that can be challenging to determine precisely by most biophysical methods. Here, we explore the dynamic range of the kinetic exclusion assay (KinExA) by exploiting the interactions of an anti-DKK antibody with a panel of DKK antigens as a model system. By tailoring the KinExA to each studied antigen, we obtained apparent equilibrium dissociation constants (KD values) spanning six orders of magnitude, from approximately 100 fM to 100 nM. Using a previously calibrated antibody concentration and working in a suitable concentration range, we show that a single experiment can yield accurate and precise values for both the apparent KD and the apparent active concentration of the antigen, thereby increasing the information content of an assay and decreasing sample consumption. Orthogonal measurements obtained on Biacore and Octet label-free biosensor platforms further validated our KinExA-derived affinity and active concentration determinations. We obtained excellent agreement in the apparent affinities obtained across platforms and within the KinExA method irrespective of the assay orientation employed or the purity of the recombinant or native antigens

Gradual caldera collapse at Bárdarbunga volcano, Iceland, regulated by lateral magma outflow

Large volcanic eruptions on Earth commonly occur with a collapse of the roof of a crustal magma reservoir, forming a caldera. Only a few such collapses occur per century, and the lack of detailed observations has obscured insight into the mechanical interplay between collapse and eruption.We usemultiparameter geophysical and geochemical data to show that the 110-squarekilometer and 65-meter-deep collapse of Bárdarbunga caldera in 2014-2015 was initiated through withdrawal of magma, and lateral migration through a 48-kilometers-long dike, from a 12-kilometers deep reservoir. Interaction between the pressure exerted by the subsiding reservoir roof and the physical properties of the subsurface flow path explain the gradual, nearexponential decline of both collapse rate and the intensity of the 180-day-long eruption

Reduction of Pavlovian bias in schizophrenia: Enhanced effects in clozapine-administered patients

The negative symptoms of schizophrenia (SZ) are associated with a pattern of reinforcement learning (RL) deficits likely related to degraded representations of reward values. However, the RL tasks used to date have required active responses to both reward and punishing stimuli. Pavlovian biases have been shown to affect performance on these tasks through invigoration of action to reward and inhibition of action to punishment, and may be partially responsible for the effects found in patients. Forty-five patients with schizophrenia and 30 demographically-matched controls completed a four-stimulus reinforcement learning task that crossed action ("Go" or "NoGo") and the valence of the optimal outcome (reward or punishment-avoidance), such that all combinations of action and outcome valence were tested. Behaviour was modelled using a six-parameter RL model and EEG was simultaneously recorded. Patients demonstrated a reduction in Pavlovian performance bias that was evident in a reduced Go bias across the full group. In a subset of patients administered clozapine, the reduction in Pavlovian bias was enhanced. The reduction in Pavlovian bias in SZ patients was accompanied by feedback processing differences at the time of the P3a component. The reduced Pavlovian bias in patients is suggested to be due to reduced fidelity in the communication between striatal regions and frontal cortex. It may also partially account for previous findings of poorer "Go-learning" in schizophrenia where "Go" responses or Pavlovian consistent responses are required for optimal performance. An attenuated P3a component dynamic in patients is consistent with a view that deficits in operant learning are due to impairments in adaptively using feedback to update representations of stimulus value