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For assessing tsunami hazard in northernmost Cascadia, there is an urgent need to define tsunami sources due to megathrust rupture. Even though the knowledge of Cascadia fault structure and rupture behaviour is limited at present, geologically and mechanically plausible scenarios can still be designed. In this work, we use three-dimensional dislocation modelling to construct three types of rupture scenarios and illustrate their effects on tsunami generation and propagation. The first type, buried rupture, is a classical model based on the assumption of coseismic strengthening of the shallowest part of the fault. In the second type, splay-faulting rupture, fault slip is diverted to a main splay fault, enhancing seafloor uplift. Although the presence or absence of such a main splay fault is not yet confirmed by structural observations, this scenario cannot be excluded from hazard assessment. In the third type, trench-breaching rupture, slip extends to the deformation front and breaks the seafloor by activating a frontal thrust. The model frontal thrust, based on information extracted from multichannel seismic data, is hypothetically continuous along strike. Our low-resolution tsunami simulation indicates that, compared to the buried rupture, coastal wave surface elevation generated by the splay-faulting rupture is generally 50–100% higher, but that by trench-breaching rupture is slightly lower, especially if slip of the frontal thrust is large (e.g. 100% of peak slip). Wave elevation in the trench-breaching scenario depends on a trade-off between enhanced short-wavelength seafloor uplift over the frontal thrust and reduced uplift over a broader area farther landward.

Highlights • The pre-dill assessment of seismic data yielded identification of total 22 gas hydrate prospective sites. • The paper details the pre-expedition studies for identification of 18 Gas hydrate prospects. • On-board dynamic review studies for delineation of pre-expedition sites also detailed. • The drilling results matched with pre-expedition prediction, validated approach adopted for gas hydrate prospecting. Abstract After completing the first expedition of India's National Gas Hydrate Program (NGHP-01) in 2006, it was concluded that for the next expedition (National Gas Hydrate Program 02; NGHP-02), a new drill site review effort should focus on identifying potential deep-water offshore gas hydrate accumulations in sand dominated depositional environments. Therefore, geological and geophysical data analysis and 3D seismic data interpretation along with associated seismic modeling were carried out in three areas of the Krishna-Godavari Basin: Areas B, C, and E. Conventional petroleum exploration approaches of seismic amplitude evaluation were adapted to prospect for potentially sand-rich depositional systems within the gas hydrate stability zone. Subsequently, these prospective areas were further assessed through the geological and geophysical evaluation of depositional setting, gas sources, and gas migration pathways. In Area B, prospecting focused on a large anticlinal structure with a prominent bottom-simulating reflector and several key horizons that indicated evidence for potential sand-hosted hydrate occurrences. In Area C, the prospects were distributed throughout various settings within a very large deep-water channel-levee-fan system with complex indications of potential gas hydrate occurrence in sand-prone seismic facies. In Area E, prospects were associated with high amplitude events within inferred channel-levee sequences. Based on the pre-expedition/onboard drill-site evaluation, the 22 most promising sites in the Krishna-Godavari Basin were identified and prioritized to investigate and delineate a total of 17 identified gas hydrate prospects. This paper describes the geo-scientific studies carried out prior to NGHP-02 for site identification, evaluation and prioritization. An important outcome of this study is the identification of two potentially producible gas hydrate systems inferred to host significant quantities of gas hydrate in stratigraphic-structural traps.

Marine acoustic data are used to map and characterize submarine slope failure along the accretionary prism of Cascadia. Two main styles of slope failure are identified: (1) failures with curved head scarps, which are predominantly associated with incoherent debris-flow deposits; and (2) failures with rectangular head scarps, which are predominantly associated with intact sediment blocks. Rectangular head scarps mostly occur on thrust ridges with slope angles

Highlights • Elongated fault structures are conduits for focused fluid flow. • Gas migration occurs only along a sub-set of faults across Opouawe bank. • Stress state deduced from 3D fault structures appears partially stratigraphically controlled. Abstract High-resolution 2D and 3D seismic data from Opouawe Bank, an accretionary ridge on the Hikurangi subduction margin off New Zealand, show evidence for exceptional gas migration pathways linked to the stress regime of the ridge. Although the ridge has formed by thrusting and folding in response to a sub-horizontal principal compressive stress (σ1), it is clear that local stress conditions related to uplift and extension around the apex of folding (i.e. sub-vertical σ1) are controlling shallow fluid flow. The most conspicuous structural features are parallel and horizontally-elongated extensional fractures that are perpendicular to the ridge axis. At shallower depth near the seafloor, extensional fractures evolve into more concentric structures which ultimately reach the seafloor where they terminate at gas seeps. In addition to the ridge-perpendicular extensional fractures, we also observe both ridge-perpendicular and ridge-parallel normal faults. This indicates that both longitudinal- and ridge-perpendicular extension have occurred in the past. The deepest stratigraphic unit that we image has undergone significant folding and is affected by both sets of normal faults. Shallower stratigraphic units are less deformed and only host the ridge-parallel normal faults, indicating that longitudinal extension was limited to an older phase of ridge evolution. Present-day gas migration has exploited the fabric from longitudinal extension at depth. As the gas ascends to shallower units it ‘self-generates’ its flow pathways through the more concentric structures near the seafloor. This shows that gas migration can evolve from being dependent on inherited tectonic structures at depth, to becoming self-propagating closer to the seafloor.

Antipsychotics are effective in treating schizophrenia but may lead to a higher cardiovascular risk due to QTc prolongation. Besides drugs, genetic and clinical factors may contribute to QTc prolongation. The aim of this study is to examine the effect of candidate genes known for QTc prolongation and their interaction with common antipsychotics. Thus, 199 patients were genotyped for nine polymorphisms in KCNQ1, KCNH2, SCN5A, LOC10537879, LOC101927066, NOS1AP and NUBPL. QTc interval duration was measured before treatment and weekly for 5 weeks while being treated with risperidone, quetiapine, olanzapine, amisulpride, aripiprazole and haloperidol in monotherapy. Antipsychotics used in this study showed a different potential to affect the QTc interval. We found no association between KCNH2, KCNQ1, LOC10537879, LOC101927066, NOS1AP and NUBPL polymorphisms and QTc duration at baseline and during antipsychotic treatment. Mixed general models showed a significant overall influence of SCN5A (H558R) on QTc duration but no significant interaction with antipsychotic treatment. Our results do not provide evidence for an involvement of candidate genes for QTc duration in the pathophysiology of QTc prolongation by antipsychotics during short-term treatment. Further association studies are needed to confirm our findings. With a better understanding of these interactions the cardiovascular risk of patients may be decreased.

High-resolution marine seismic data acquisition and subsequent analyses are highly influenced by sea conditions, directly affecting data quality and interpretation. Traditional swell effect correction methods are effective in improving reflector continuity; however, they are less useful for enhancing travel time consistency at intersection points of crossing lines. To develop a robust swell-removal technique for a set of crossing lines multi-beam echo sounder (MBES) data and Chirp sub-bottom profiler (SBP) data were acquired. After generation of a time structure map of the sea-bottom converted from the final processed multi-beam data, a moving average was used to improve the event continuity of the sea-bottom reflection of the Chirp SBP data. Using the position of the Chirp SBP data, the difference between the travel time of the sea-bottom from the smoothed map and the original travel time of the sea-bottom is calculated as a static correction. The static correction method based on the MBES data was compared and verified using three different cases: (i) simple 2D swell effect correction on a line-by-line basis, (ii) comparing the swell corrections at the crossing positions of 2D lines acquired from different dates, and (iii) comparison of ties of intersection points between 2D lines after new swell correction applied. Although a simple 2D swell correction showed great enhancement of reflector continuity, only the full static correction using the newly proposed method using MBES data produced completely corrected reflection events especially at the crossing points of 2D lines.

Highlights • Dual-vergence structure is observed for the first time on the northern Cascadia margin. • Around central Vancouver Island, vergence switches from seaward in the south to landward in the north. • First OBS migration study imaging the top of the igneous oceanic crust using only a small airgun source (120 in.3). • OBS migration indicates that an OBS, in water depths up to 2.5 km, can image up to 5 km on either side of its seafloor position. Abstract The detailed structure of the northern Cascadia basin and frontal ridge region was obtained using data from several widely spaced ocean bottom seismometers (OBSs). Mirror imaging was used in which the downgoing multiples (mirror signal) are migrated as they provide information about a much larger area than imaging with primary signal alone. Specifically, Kirchhoff time migration was applied to hydrophone and vertical geophone data. Our results indicate remarkable structures that were not observed on the northern Cascadia margin in previous single-channel or multi-channel seismic (MCS) data. Results show that, in these water depths (2.0–2.5 km), an OBS can image up to 5 km on either side of its position on the seafloor and hence an OBS spacing of 5 km is sufficient to provide a two-fold migration stack. Results also show the top of the igneous oceanic crust at 5–6 km beneath the seafloor using only a small airgun source (120 in.3). Specifically, OBS migration results clearly show the continuity of reflectors which enabled the identification of frontal thrusts and a main thrust fault. These faults indicate, for the first time on this margin, the presence of a dual-vergence structure. These kinds of structures have so far been observed in < 0.5% of modern convergent margins and could be related to horizontal compression associated with subduction and low basal shear stress resulting from over-pressure. Reanalysis of previous MCS data from this region augmented the OBS migration results and further suggests that the vergence switches from seaward to landward around central Vancouver Island. Furthermore, fault geometry analyses indicate that the total amount of shortening accommodated due to faulting and folding is about 3 km, which suggest that thrusting would have started at least ∼ 65 ky ago.

Highlights • Multiple submarine landslide scars occur on the Beaufort Continental Slope. • Scars are left by large-scale Late Holocene retrogressive slope failures. • Scars coalesce downslope to form basin wide feature at ≥1200 m depths. • Failure planes are at 30–75 depths within rapidly deposited glaciomarine sediments. • Widespread brackish water infusion into failure zone preconditions slope for failure. Exploration of the continental slope of the Canadian Beaufort Sea has revealed a remarkable coalescence of slide scars with headwalls between 130 and 1100 m water depth (mwd). With increased depth, the scars widen and merge into one gigantic regional slide scar that is more than 100 km wide below ~1100 mwd. To understand the development of these features, five sites were investigated with an Autonomous Underwater Vehicle, which provided 1-m bathymetric grids and Chirp profiles, and surveyed with a Remotely Operated Vehicle. The morphologies are consistent with retrograde failures that occurred on failure planes located between 30 and 75 m below the modern seafloor. At issue is whether the continental slope in this area is preconditioned for failure. While rapid sedimentation during glacial periods, and the presence of shallow gas cannot be ruled out, given the geological environment, it is unclear that they are primary preconditioning factors. Evidence of widespread flushing of the slope with brackish waters, and observed flows of brackish water within slide scars, suggest fluid venting and overpressure may play a role in the development of the extensive slope failures seen along this margin. The impact of pore water salinity changes at the depth of the failure plane on slope stability has not been considered in marine settings previously.

A global inventory of data from gas hydrate drilling expeditions is used to develop relationships between the base of structure I gas hydrate stability, top of gas hydrate occurrence, sulfate-methane transition depth, pressure (water depth), and geothermal gradients. The motivation of this study is to provide first-order estimates of the top of gas hydrate occurrence and associated thickness of the gas hydrate occurrence zone for climate-change scenarios, global carbon budget analyses, or gas hydrate resource assessments. Results from publically available drilling campaigns (21 expeditions, 52 drill sites) off Cascadia, Blake Ridge, India, Korea, South China Sea, Japan, Chile, Peru, Costa Rica, Gulf of Mexico, and Borneo reveal a first-order linear relationship between the depth to the top and base of gas hydrate occurrence. The reason for these nearly linear relationships is believed to be the strong pressure- and temperature dependence of methane solubility in the absence of large difference in thermal gradients between the various sites assessed. In addition, a statistically robust relationship was defined between the thickness of the gas hydrate occurrence zone and the base of gas hydrate stability (in meters below seafloor). The relationship developed is able to predict the depth of the top of gas hydrate occurrence zone using observed depths of the base of gas hydrate stability within less than 50 meters at most locations examined in this study. No clear correlation of the depth to the top and base of gas hydrate occurrences with geothermal gradient and sulfate-methane transition depth were identified.

Background The objective of this study is to test the conflicting theories concerning the association of negative self and other schemata and paranoid ideation. Methods A risk-based approach, including risk stratification, is used to gain insight into the association of the negative self and other schemata that may be shared by individuals or differentiate between individuals at clinical high risk (CHR) for a first-episode psychosis and those with full-blown psychosis. The dataset includes a sample of individuals at CHR (n = 137) and a sample of individuals with persisting positive symptoms (PPS, n = 211). The CHR sample was subdivided according to a prognostic index yielding 4 CHR sub-classes with increasing risk for transition to psychosis. Results Negative beliefs about the self were associated with paranoid ideation in CHR and a lower risk state. In the highest risk state and full-blown psychosis, there is an association with negative beliefs about others. Conclusion These findings are in line with theories suggesting a switch from a predominantly activated negative self-schema to a malevolent others-schema in association with paranoid ideation along the risk-continuum. However, due to methodological limitations these results should be replicated by future studies.

The aim of this study was to evaluate antidepressant add-on treatment within the acute treatment of schizophrenia spectrum disorder patients. Antidepressant add-on was evaluated in 365 patients within a naturalistic multicenter study. Patients with/without antidepressant add-on were compared regarding clinical and treatment-related variables, response and remission, and remission of depressive and negative symptoms. The efficacy of antidepressant add-on treatment was furthermore analyzed applying marginal structure models. Twenty-three percent of the patients received antidepressant add-on for a mean duration of 50.28 (33.42) days. Patients with the diagnosis of a schizoaffective disorder, multiple illness episodes, and a longer duration of their illness as well as those with significantly fewer baseline positive symptoms, more negative and depressive symptoms, more side effects, and less subjective well-being were augmented with antidepressants. At discharge no significant effect of antidepressant add-on treatment was observed in terms of a 25% improvement (p=0.2623), a 50% improvement (p=0.3946), remission (p=0.0552), or remission of depressive (p=0.6336) and negative symptoms (p=0.8756). Also, when analyzing marginal structure models considering the diagnostic subgroups, no significant effect was found. Add-on with antidepressants is common. A final recommendation in terms of this strategy’s efficacy cannot be given.

The ability to inhibit inappropriate responses and suppress irrelevant information is a core feature of executive control. In this study, we provide a detailed analysis of prepotent response inhibition and interference in patients with schizophrenia. To further test the role of genetic factors and subclinical schizophrenia-like traits, we additionally studied clinically unaffected, first-degree relatives of schizophrenia patients and assessed dimensions of schizotypy in both relatives and healthy controls. Inhibition and interference control were assessed using a battery comprising the antisaccade, Stroop, stop signal, go/no-go, flanker, and Simon tasks. Schizophrenia patients differed from both relatives and controls in making more errors on the antisaccade task and having longer response times on the Stroop task, especially the incongruent condition. Patients also had general, that is, condition independent, increases in reaction times on the go/no-go and flanker tasks and made more errors on the flanker and Simon tasks, suggesting general performance impairments independent of inhibitory demand. Relatives were characterized by hypometric antisaccade amplitude gain despite normal prosaccades, suggesting a selective deficit in non-standard sensorimotor transformations. Schizotypy was correlated with inhibitory performance across a number of tasks in both relatives and controls. Generally, these effects were independent of verbal intelligence levels. Overall, the findings point to rather selective impairments of inhibitory control in the schizophrenia spectrum and confirm a previously observed deficit in antisaccade spatial accuracy as an endophenotype of schizophrenia.

NEUROD2 is a neurospecific helix-loop-helix transcription factor which has an impact on the regulation of glutamatergic and GABAergic genes. We investigated an association of NEUROD2 with neurocognitive dysfunctions in schizophrenia and schizoaffective disorder patients before and during treatment with different second-generation antipsychotics.Patients were genotyped for four different polymorphisms of the NEUROD2 gene ((rs9889354(A/G), rs1877032(C/T), rs12453682(C/T) and rs11078918(C/G)). Cognitive function was assessed at baseline and week 8. Results of individual neuropsychological tests were assigned to six cognitive domains (reaction time and quality; executive function; working, verbal and visual memory) and a general cognitive index.167 patients were included in the study. The NEUROD2 exonic polymorphism rs11078918 showed significant associations with verbal memory and executive functions, whereas the NEUROD2 polymorphism rs12453682 was significantly associated with working and verbal memory, executive functions and with a cognitive index. Significant associations were found at baseline and after eight weeks. Moreover, significant associations between the change in neuropsychological test results during antipsychotic treatment and the NEUROD2 polymorphisms rs11078918 and rs12453682 were observed.Our findings suggest that the NEUROD2 gene could play a role in the pathophysiology of neurocognitive dysfunctions as well as in the change of cognitive symptoms under antipsychotic treatment in schizophrenia and schizoaffective disorder.

Cuticular waxes play an important role in the defence system of plants. To date, reports on the chemistry of waxes from the genus Fragaria L. are very scarce and only related to the cultivated strawberry F. × ananassa. In this study, the chemical composition of cuticular waxes in different genotypes of strawberries are described for the first time extensively. Cuticular waxes were then extracted separately from the ad- and abaxial surfaces of fully developed and pathogen free leaves from greenhouse cultivation using chloroform as an apolar organic solvent. Additionally, for adaxial surfaces the epi- and intracuticular wax layers were analysed separately. The quantitative composition was studied by gas chromatography (GC) with flame ionisation detection and single compounds were identified by coupled GC-mass spectrometry. Substantial differences in total mass and relative composition between the ab- and adaxial leaf sides and between different genotypes were detected with alkanes, fatty acid alkyl esters and aldehydes representing major compound classes. Other aliphatic compounds, triterpenoids and non-identified substances were detected only in minor quantities. Additionally, cinnamic acid alkyl esters were found exclusively on adaxial sides whereas secondary alcohols were only present on abaxial sides. Similar differences could be detected between the epi- and intracuticular layer of adaxial leaf surface. The chemistry of cuticular waxes can influence infection processes of pathogens in different ways. Therefore, the obtained results can be used in forthcoming investigations about resistances to fungal, bacterial and animal pathogens.

Summary Genome editing in induced pluripotent stem cells is currently hampered by the laborious and expensive nature of identifying homology-directed repair (HDR)-modified cells. We present an approach where isolation of cells bearing a selectable, HDR-mediated editing event at one locus enriches for HDR-mediated edits at additional loci. This strategy, called co-targeting with selection, improves the probability of isolating cells bearing HDR-mediated variants and accelerates the production of disease models., Graphical Abstract, Highlights • Increases the efficiency of genome editing in human iPSCs • Enhances detectability of variants of interest derived by homology-directed repair • Is a simple, scalable, and adaptable strategy for knocking in variants of interest, The potential of CRISPR/Cas9-based genome editing in iPSCs is currently hampered by the laborious nature of identifying cells modified by the lesser-used homology-directed repair (HDR) pathway. Geurts, McDermott-Roe, and colleagues present a straightforward approach, co-targeting with selection, based on co-modification that enriches for cells undergoing HDR thereby improving targeting efficiencies.

The presence of a wedge of offshore permafrost on the shelf of the Canadian Beaufort Sea has been previously recognized and the consequence of a prolonged occurrence of such permafrost is the possibility of an underlying gas hydrate regime. We present the first evidence for wide-spread occurrences of gas hydrates across the shelf in water depths of 60–100 m using 3D and 2D multichannel seismic (MCS) data. A reflection with a polarity opposite to the seafloor was identified ∼1000 m below the seafloor that mimics some of the bottom-simulating reflections (BSRs) in marine gas hydrate regimes. However, the reflection is not truly bottom-simulating, as its depth is controlled by offshore permafrost. The depth of the reflection decreases with increasing water depth, as predicted from thermal modeling of the late Wisconsin transgression. The reflection crosscuts strata and defines a zone of enhanced reflectivity beneath it, which originates from free gas accumulated at the phase boundary over time as permafrost and associated gas hydrate stability zones thin in response to the transgression. The wide-spread gas hydrate occurrence beneath permafrost has implications on the region including drilling hazards associated with the presence of free gas, possible overpressure, lateral migration of fluids and expulsion at the seafloor. In contrast to the permafrost-associated gas hydrates, a deep-water marine BSR was also identified on MCS profiles. The MCS data show a polarity-reversed seismic reflection associated with a low-velocity zone beneath it. The seismic data coverage in the southern Beaufort Sea shows that the deep-water marine BSR is not uniformly present across the entire region. The regional discrepancy of the BSR occurrence between the US Alaska portion and the Mackenzie Delta region may be a result of high sedimentation rates expected for the central Mackenzie delta and high abundance of mass-transport deposits that prohibit gas to accumulate within and beneath the gas hydrate stability zone.

To develop gas hydrates as a potential energy source, geophysical surveys and geological studies of gas hydrates in the Ulleung Basin, East Sea off the east coast of Korea have been carried out since 1997. Bottom-simulating reflector (BSR), initially used indicator for the potential presence of gas hydrates was first identified on seismic data acquired in 1998. Based on the early results of preliminary R&D project, 12367 km of 2D multichannel reflection seismic lines, 38 piston cores, and multi-beam echo-sounder data were collected from 2000 to 2004. The cores showed high amounts of total organic carbon and high residual hydrocarbon gas levels. Gas composition and isotope ratios define it as of primarily biogenic origin. In addition to the BSRs that are widespread across the basin, numerous chimney structures were found in seismic data. These features indicate a high potential of the Ulleung Basin to host significant amounts of gas hydrate. Dedicated geophysical surveys, geological and experimental studies were carried out culminating in two deep drilling expeditions, completed in 2007 and 2010. Sediment coring (including pressure coring), and a comprehensive well log program complements the regional studies and were used for a resource assessment. Two targets for a future test-production are currently proposed: pore-filling gas hydrate in sand-dominated sediments and massive occurrences of gas hydrate within chimney-like structures. An environmental impact study has been launched to evaluate any potential risks to production.

A pseudo 3-D Chirp sub-bottom profiler (SBP) survey was conducted to define the extension of a fault that was previously identified on low-resolution 2-D seismic data with an emphasis on the shallow sedimentary layers and to determine if the fault extends to the seafloor. The geophysical survey was conducted as part of an environmental impact assessment for a proposed gas hydrate production test in the Ulleung Basin, East Sea. The Chirp SBP raw data were acquired over an area of 1 km × 1 km with an average line spacing of 20 m. To produce a 3-D Chirp SBP volume, we developed an optimal processing sequence that was divided into two steps. The first phase of 2-D data processing included a sweep signature estimation, correlation, deconvolution, swell effect correction, and migration. The second phase of 3-D data processing was composed of a bin design, bin gathering of the final processed 2-D data set, amplitude normalization, and residual statics correction. The 3-D Chirp SBP volume provides enhanced imaging especially due to the residual static processing using a moving average method and shows better continuity of the sedimentary layers and consistency of the reflection events than the individual 2-D lines. Deformation of the seafloor as a result of the fault was detected, and the fault offset increases in the deeper sedimentary layers. We also determined that the fault strikes northwest-southeast. However, the shallow sub-seafloor sediments have high porosities and therefore do not exhibit brittle fault-behavior but rather deform continuously due to fault movement.

Despite being recommended for use in clinical trials, the consensus remission criteria were found to leave patients with persisting symptoms, relevant areas of functional impairment and a decreased sense of wellbeing. Therefore, to evaluate the appropriateness of the schizophrenia consensus criteria, a definition of remission based on the Clinical Global Impression Scale (CGI) was developed and remitter subgroups were compared.239 patients with a schizophrenia spectrum disorder were evaluated regarding their remission status after inpatient treatment. Remission in schizophrenia was defined according to the symptom-severity component of the consensus criteria by Andreasen et al. and a CGI based definition was calculated using sensitivity and specificity using receiver operating curves (asymptomatic remitter). Both remitter groups (schizophrenia consensus versus asymptomatic remitters) were compared regarding different clinical variables at discharge as well as the likelihood to relapse within a 1-year follow-up period. Both schizophrenia remitter subgroups were compared to remitters in major depression as a reference value.Following the consensus criteria, 63% of the schizophrenia patients were in remission compared to only 18% following the asymptomatic criterion. The schizophrenia consensus remitters were less likely to be concurrent treatment responders (p 0.0001), had a significantly greater illness severity (p 0.0001) and less functioning (p = 0.0358) as well as a significantly greater risk to relapse (p = 0.0174) compared to the schizophrenia asymptomatic remitters as well as the depressed remitters.It should be critically re-evaluated if the currently proposed consensus criteria are adequate to measure what is traditionally understood to be remission.

The Nootka fault zone is a ridge‐trench‐trench transform fault that was initiated ~4 Ma when the Explorer ridge became independent of the Juan de Fuca ridge. Multibeam data around the fault zone and a compilation of several seismic reflection surveys provide insight into initiation of strike‐slip faults. Previous interpretations assumed that the two faults seen cutting the seafloor are subparallel to shear between the Explorer and Juan de Fuca plates and formed instantaneously at 4 Ma. Increased data density shows that these faults are subparallel to seafloor magnetic anomalies and appear to have utilized extensional faults formed at the ridge. They are surrounded by numerous buried steeply dipping, small‐offset growth faults; at least some of which are likely still active. Our observations corroborate analogue models of strike‐slip fault initiation that predict formation of Riedel‐like shears within a zone of faulting and that displacement localizes over time. The existence of several long subparallel faults and a very wide zone of faulting has been predicted by models of distributed shear at depth. Along the Nootka fault zone basement has risen by several hundred meters and bright reversed‐polarity reflectors some of which are interpreted to be methane hydrate reflectors are common. Hydration, likely as serpentinization, of the upper mantle could explain both sets of observations: Serpentinization can result in a 30–50% volume expansion and methane is observed in vents driven by this process. Biogenic sources of methane are likely to be present and concentrated by currently active fluid flow in the faulted sediments.

Highlights • First chronology of post glacial mass transport deposits in Canadian Beaufort Sea. • Chrono-stratigraphy based on 14C dating of foraminifera and shells. • Type-section seismo-stratigraphy from sub-bottom profiler data was established. • Average recurrence rate of 1 failure event per 1000 yrs., but events are clustered. • Highest number of failure events just prior to the Younger Dryas. Abstract Extent and chronology of 24 buried and seabed-exposed mass transport deposits (MTDs) on the continental slope of the Canadian Beaufort Sea were compiled towards a regional geo-hazard assessment of the Beaufort region. A total of 2220 lines of 3.5 kHz sub-bottom profiler (SBP) data (~40,000-line kilometres) covering an area of 9740 km2 were analyzed to allow a new understanding of slope instability in the region. Several sediment cores acquired across the region allow dating of the sediment cover. A regionally representative seismic-stratigraphy (type section, ca. 60 m thick) of the stratified sediments mantling the slope was defined. The MTDs all occur above a marked change in sedimentation style from a deeper-situated slope fan that varies substantially laterally to the above-lying stratified layers that host the MTDs. The type section comprises three sedimentary units bound by two prominent markers. Relative ages for the MTDs were defined by measuring the thickness of sediments overlying each MTD and linking that sediment package to the type section. Two 3-D seismic data volumes across the study region verified interpretations from 2D data by imaging internal deposit character and down-slope continuity of the MTDs. Seismic amplitude and similarity attributes enabled identification of further MTD events, incompletely imaged by the SBP data. A composite chronostratigraphy based on 14C dating of foraminifera and shells was assembled despite the fact that the type section is far thicker than sediment coring limits. Sub-unit thickness varies up- and down-slope such that a selection of cores across the study region enabled its compilation. The marked change in sedimentation style at the base of the type section required substantial extrapolation to date. Simple (quadratic function) age models project that the base of the type section signals the end of the last glacial maximum (Wisconsinan, or marine isotope stage 2 glaciation) and initiation of pro-glacial plume sedimentation (the deglacial), and finally post-glacial (marine) ultimately from the Mackenzie River. The MTD abundance above this contact defines an average theoretical recurrence rate of one MTD per ~1000 yrs.; however, MTDs are clustered temporally with the highest number of events occurring just prior to the onset of the Younger Dryas at around 13 ka BP (cal.).

Highlights • MeBo drilling in Danube fan down to 147 m recovered limnic to marine deposits. • Molecular and stable isotope characterization of light hydrocarbons, CO2, and H2O. • H and O isotopic compositions of pore water reflect paleoclimate variations. • Isotope relations prove microbial carbonate reduction as major methanogenic pathway. • Control of δ2H–CH4 by δ2H–H2O may lead to misinterpretation of methanogenic paths. Abstract We report on the geochemistry of light hydrocarbons and pore water in sediments down to 147 m below seafloor (mbsf), at two sites within the gas hydrate stability field of the Danube deep-sea fan, Black Sea. Sediments were drilled with MARUM-MeBo200 and comprise the transition from limnic to the recent marine stage. Stable C/N ratios (mean 5.1 and 5.6) and δ13C-Corg values (mean −25.8‰ V-PDB) suggest relatively uniform bulk organic matter compositions. In contrast, pore water δ2H and δ18O values varied considerably from approx. −120‰ to −30‰ V-SMOW and from −15‰ to −3‰ V-SMOW, respectively. These data pairs plot close to the ‘Global Meteoric Water Line’ and indicate paleo temperature variations. Depletions of pore water in 2H and 18O below 40 mbsf indicate low temperatures and likely reflect conditions during (the) last glacial period(s). Methane was much more abundant than the only other hydrocarbons found in notable concentrations, ethane and propane ((C1/(C2+C3) ≥20,000). Relatively constant δ13C–CH4 (~−70‰ V-PDB) and δ13C–C2H6 (~−52‰ V-PDB) values with depth indicate that methane and ethane are predominantly of microbial origin and that their formation was not limited by carbon availability. In contrast, δ2H–CH4 values varied in a large range (approx. −310 to −240‰ V-SMOW) with depth and positively correlated with trends observed for δ2H–H2O. Isotope separations (Δδ13C(CH4–CO2), Δδ2H(CH4–H2O)) substantiate that microbial carbonate reduction (CR) is the prevalent methanogenic pathway throughout the sediments irrespective of their geochemical history. Remarkably, in δ13C–CH4 – δ2H–CH4 diagrams widely used, samples characterized by δ2H–CH4 values more negative than approx. −250‰ plot out of the field assigned for pure CR. We conclude that assignments of microbial methanogenic pathways based on classical interpretations of δ13C–CH4 – δ2H–CH4 pairs can lead to misinterpretations, as severe 2H-depletions of methane formed through microbial CR can result from 2H-depletions of the pore water generated during low-temperature climatic periods.

Highlights • Hypocenters within the subducted Explorer plate indicate slab deformation. • The oceanic slab is bending downward toward the northwest. • A complex sequence of focal mechanisms also indicates plate deformation. • Decreased seismic activity in the overriding plate indicates decoupling to the NW. • Deformation and decoupling could limit megathrust rupture propagation. Abstract At the northernmost extent of the Cascadia subduction zone, the Explorer plate subducts at approximately 2 cm/yr, less than half the rate of the Juan de Fuca plate to the south. The boundary between these two plates is known as the Nootka fault zone, which is one of the focuses of the Seafloor Earthquake Array Japan-Canada Cascadia Experiment (SeaJade). During this survey, an 6.4 earthquake occurred on 24 April 2014. This event and the subsequent aftershocks (referred to as the Nootka Sequence) reveal an approximately 40-km-long subducted fault within the Explorer Plate to the north of the Nootka fault zone. We infer that the fault is a subducted conjugate fault because of its nearly identical orientation to those seaward of the subduction front within the Nootka fault zone. The depth distribution and focal mechanisms of the aftershocks indicate significant margin-parallel deformation of the subducting plate. The subduction interface at the Nootka Sequence fault has been deflected downward to the northwest from a depth of approximately 15 – 25 km over a distance of 25 km. We propose two possible scenarios that are modified from previously suggested slab-tear model with induced margin-parallel mantle flow to explain the significant deformation of the young, warm subducting Explorer plate. To the northwest of this change in slab geometry, a lack of seismic activity above the plate interface indicates that the Explorer plate has partially decoupled from the overriding North America plate. We conclude that the geometric variation separating the southern Explorer plate from the north, along with decoupling and a possible intraslab tear, may be a significant combination to resist the propagation of a megathrust rupture across this boundary.

Nonspecific lipid transfer proteins reversibly bind different types of lipid molecules in a hydrophobic cavity. They facilitate phospholipid transfer between membranes in vitro, play a role in cuticle and possibly in suberin formation, and might be involved in plant pathogen defense signaling. This study focuses on the role of the lipid transfer protein AtLTPI-4 in crown gall development. Arabidopsis (Arabidopsis thaliana) crown gall tumors, which develop upon infection with the virulent Agrobacterium tumefaciens strain C58, highly expressed AtLTPI-4. Crown galls of the atltpI-4 loss-of-function mutant were much smaller compared with those of wild-type plants. The gene expression pattern and localization of the protein to the plasma membrane pointed to a function of AtLTPI-4 in cell wall suberization. Since Arabidopsis crown galls are covered by a suberin-containing periderm instead of a cuticle, we analyzed the suberin composition of crown galls and found a reduction in the amounts of long-chain fatty acids (C18:0) in the atltpI-4 mutant. To demonstrate the impact of AtLtpI-4 on extracellular lipid composition, we expressed the protein in Arabidopsis epidermis cells. This led to a significant increase in the very-long-chain fatty acids C24 and C26 in the cuticular wax fraction. Homology modeling and lipid-protein-overlay assays showed that AtLtpI-4 protein can bind these very-long-chain fatty acids. Thus, AtLtpI-4 protein may facilitate the transfer of long-chain as well as very-long-chain fatty acids into the apoplast, depending on the cell type in which it is expressed. In crown galls, which endogenously express AtLtpI-4, it is involved in suberin formation.

During Integrated Ocean Drilling Program Expedition 311 five boreholes were drilled across the accretionary prism of the northern Cascadia subduction zone. Logging-while-drilling borehole images are utilized to determine breakout orientations to define maximum horizontal compressive stress orientations. Additionally, wireline logging data at two of these sites and from Site 889 of Ocean Drilling Program Leg 146 are used to define breakouts from differences in the aperture of caliper arms. At most sites, the maximum horizontal compressive stress SHmax is margin-normal, consistent with plate convergence. Deviations from this trend reflect local structural perturbations. Our results do not constrain stress magnitudes. If the margin-normal compressional stress is greater than the vertical stress, the margin-normal SHmax direction we observe may reflect current locking of a velocity-weakening shallow megathrust and thus potential for trench-breaching, tsunamigenic rupture in a future megathrust earthquake.

Long-term monitoring over one year revealed high temporal variability of gas emissions at a cold seep in 1250 m water depth offshore Vancouver Island, British Columbia. Data from the North East Pacific Time series Underwater Networked Experiment observatory operated by Ocean Networks Canada were used. The site is equipped with a 260 kHz Imagenex sonar collecting hourly data, conductivity-temperature-depth sensors, bottom pressure recorders, current meter, and an ocean bottom seismograph. This enables correlation of the data and analyzing trigger mechanisms and regulating criteria of gas discharge activity. Three periods of gas emission activity were observed: (a) short activity phases of few hours lasting several months, (b) alternating activity and inactivity of up to several day-long phases each, and (c) a period of several weeks of permanent activity. These periods can neither be explained by oceanographic conditions nor initiated by earthquakes. However, we found a clear correlation of gas emission with bottom pressure changes controlled by tides. Gas bubbles start emanating during decreasing tidal pressure. Tidally induced pressure changes also influence the subbottom fluid system by shifting the methane solubility resulting in exsolution of gas during falling tides. These pressure changes affect the equilibrium of forces allowing free gas in sediments to emanate into the water column at decreased hydrostatic load. We propose a model for the fluid system at the seep, fueled by a constant sub-surface methane flux and a frequent tidally controlled discharge of gas bubbles into the ocean, transferable to other gas emission sites in the world's oceans.

Mutations of HSPB5 (also known as CRYAB or αB-crystallin), a bona fide heat shock protein and molecular chaperone encoded by the HSPB5 (crystallin, alpha B) gene, are linked to various multisystem disorders featuring variable combinations of cataracts, cardiomyopathy, and skeletal myopathy. This study aims at investigating the pathological mechanisms involved in an early onset myofibrillar myopathy manifesting in a child harboring a homozygous recessive mutation in HSPB5, 343delT. To study HSPB5 343delT protein dynamics, we utilize model cell culture systems including induced pluripotent stem cells (iPSCs) derived from the 343delT patient (343delT/343delT) along with isogenic, heterozygous, gene-corrected control cells (WT KI/343delT), and BHK21 cells, a cell line lacking endogenous HSPB5 expression. 343delT/343delT and WT KI/343delT iPSC-derived skeletal myotubes (iSKMs) and cardiomyocytes (iCMs) did not express detectable levels of 343delT protein, contributable to extreme insolubility of the mutant protein. Overexpression of HSPB5 343delT resulted in insoluble mutant protein aggregates and induction of a cellular stress response. Co-expression of 343delT with WT prevented visible aggregation of 343delT and improved its solubility. Additionally, in vitro refolding of 343delT in the presence of WT rescued its solubility. We demonstrate an interaction between WT and 343delT both in vitro and within cells. These data support a loss of function model for the myopathy observed in the patient, as the insoluble mutant would be unavailable to perform normal functions of HSPB5, though additional gain-of-function effects of the mutant protein cannot be excluded. Additionally, our data highlights the solubilization of 343delT by WT, concordant with the recessive inheritance of the disease and absence of symptoms in carrier individuals.

Objective— This study examined vascular actions of angiotensin 1–7 (ANG 1–7) in human atrial and adipose arterioles. Approach and Results— The endothelium-derived hyperpolarizing factor of flow-mediated dilation (FMD) switches from antiproliferative nitric oxide (NO) to proatherosclerotic hydrogen peroxide in arterioles from humans with coronary artery disease (CAD). Given the known vasoprotective properties of ANG 1–7, we tested the hypothesis that overnight ANG 1–7 treatment restores the NO component of FMD in arterioles from patients with CAD. Endothelial telomerase activity is essential for preserving the NO component of vasodilation in the human microcirculation; thus, we also tested whether telomerase activity was necessary for ANG 1–7–mediated vasoprotection by treating separate arterioles with ANG 1–7±the telomerase inhibitor 2-[[(2E)-3-(2-naphthalenyl)-1-oxo-2-butenyl1-yl]amino]benzoic acid. ANG 1–7 dilated arterioles from patients without CAD, whereas dilation was significantly reduced in arterioles from patients with CAD. In atrial arterioles from patients with CAD incubated with ANG 1–7 overnight, the NO synthase inhibitor NG-nitro- l -arginine methyl ester abolished FMD, whereas the hydrogen peroxide scavenger polyethylene glycol catalase had no effect. Conversely, in vessels incubated with ANG 1–7+2-[[(2E)-3-(2-naphthalenyl)-1-oxo-2-butenyl1-yl]amino]benzoic acid, NG-nitro- l -arginine methyl ester had no effect on FMD, but polyethylene glycol catalase abolished dilation. In cultured human coronary artery endothelial cells, ANG 1–7 significantly increased telomerase activity. These results indicate that ANG 1–7 dilates human microvessels, and dilation is abrogated in the presence of CAD. Furthermore, ANG 1–7 treatment is sufficient to restore the NO component of FMD in arterioles from patients with CAD in a telomerase-dependent manner. Conclusions— ANG 1–7 exerts vasoprotection in the human microvasculature via modulation of telomerase activity.

Bathymetric data reveal abundant submarine landslides along the deformation front of the northern Cascadia margin that might have significant tsunami potential. Radiocarbon age dating showed that slope failures are early to mid-Holocene. The aim of this study is the analysis of slope stability to investigate possible trigger mechanisms using the factor of safety analysis technique on two prominent frontal ridges. First-order values for the earthquake shaking required to generate instability are derived. These are compared to estimated ground accelerations for large (M=5 to 8) crustal earthquakes to giant (M=8 to 9) megathrust events. The results suggest that estimated earthquake accelerations are insufficient to destabilize the slopes, unless the normal sediment frictional resistance is significantly reduced by, for example, excess pore pressure. Elevated pore pressure (overpressure ratio of 0.4) should significantly lower the threshold for earthquake shaking, so that a medium-sized M=5 earthquake at 10 km distance may trigger submarine landslides. Preconditioning of the slopes must be limited primarily to the mid- to early Holocene as slope failures are constrained to this period. The most likely causes for excess pore pressures include rapid sedimentation at the time of glacial retreat, sediment tectonic deformation, and gas hydrate dissociation as result of ocean warming and sea level rise. No slope failures comparable in size and volume have occurred since that time. Megathrust earthquakes have occurred frequently since the most recent failures in the mid-Holocene, which emphasizes the importance of preconditioning for submarine slope stability.

Supplemental Digital Content is available in the text., Rationale: Telomerase is a nuclear regulator of telomere elongation with recent reports suggesting a role in regulation of mitochondrial reactive oxygen species. Flow-mediated dilation in patients with cardiovascular disease is dependent on the formation of reactive oxygen species. Objective: We examined the hypothesis that telomerase activity modulates microvascular flow-mediated dilation, and loss of telomerase activity contributes to the change of mediator from nitric oxide to mitochondrial hydrogen peroxide in patients with coronary artery disease (CAD). Methods and Results: Human coronary and adipose arterioles were isolated for videomicroscopy. Flow-mediated dilation was measured in vessels pretreated with the telomerase inhibitor BIBR-1532 or vehicle. Statistical differences between groups were determined using a 2-way analysis of variance repeated measure (n≥4; P

Background After a first episode in schizophrenia guidelines recommend antipsychotic maintenance treatment (MT) for at least 1 year. Recent RCTs on subsequent targeted intermittent treatment (IT) after stepwise drug discontinuation yielded noticeably higher relapse rates than during MT also in first-episode patients. Nevertheless, about 50% of patients remain stable under IT. Given the potential adverse effects of antipsychotics and the preference of many patients to discontinue drugs, valid predictors for the feasibility of IT are urgently needed to support decision making. Methods Based on a one-year RCT phase comparing MT with IT in first-episode patients after 1 year of MT, conducted within the German Research Network on Schizophrenia (GRNS), predictors for deterioration under IT in 19 feasible patients were identified by logistic regression analysis. Results Deterioration occurred in 10 patients (52.6%). Univariate analyses indicated a lower PANSS positive score after acute treatment as well as after one year of MT as significant predictors; in multivariate logistic regression, in addition to the lower PANSS positive score after acute treatment, reaching enduring remission and having had a deterioration both during MT evolved as significant predictors and indicate a higher risk for deterioration. Conclusions Although limited by the small sample size, our findings suggest that patients who show a favorable response and full and enduring symptom remission during antipsychotic treatment, as well as those with marked deterioration despite MT should rather be recommended to remain on treatment because they are at higher risk for symptom re-exacerbation after (stepwise) drug discontinuation.

Long‐term warming of the continental shelf of the Canadian Beaufort Sea caused by the transgression associated with the last deglaciation may be causing decomposition of relict offshore subsea permafrost and gas hydrates. To evaluate this possibility, pore waters from 118 sediment cores up to 7.3‐m long were taken on the shelf and slope and analyzed for chloride concentrations and δ180 and δD composition. We observed downcore decreases in pore waters Cl− concentration in sediments from all sites from the inner shelf (

An edited version of this paper was published by AGU. Copyright 2018 American Geophysical Union. Source at https://doi.org/10.1002/2017GC007288. During expedition MARIA S. MERIAN MSM57/2 to the Svalbard margin offshore Prins Karls Forland, the seafloor drill rig MARUM‐MeBo70 was used to assess the landward termination of the gas hydrate system in water depths between 340 and 446 m. The study region shows abundant seafloor gas vents, clustered at a water depth of ∼400 m. The sedimentary environment within the upper 100 m below seafloor (mbsf) is dominated by ice‐berg scours and glacial unconformities. Sediments cored included glacial diamictons and sheet‐sands interbedded with mud. Seismic data show a bottom simulating reflector terminating ∼30 km seaward in ∼760 m water depth before it reaches the theoretical limit of the gas hydrate stability zone (GHSZ) at the drilling transect. We present results of the first in situ temperature measurements conducted with MeBo70 down to 28 mbsf. The data yield temperature gradients between ∼38°C km−1 at the deepest site (446 m) and ∼41°C km−1 at a shallower drill site (390 m). These data constrain combined with in situ pore‐fluid data, sediment porosities, and thermal conductivities the dynamic evolution of the GHSZ during the past 70 years for which bottom water temperature records exist. Gas hydrate is not stable in the sediments at sites shallower than 390 m water depth at the time of acquisition (August 2016). Only at the drill site in 446 m water depth, favorable gas hydrate stability conditions are met (maximum vertical extent of ∼60 mbsf); however, coring did not encounter any gas hydrates.

Introduction The aim of this double-blind randomized study was to evaluate the response to antipsychotic treatment in schizophrenia patients with predicted high/low risk of nonresponse identified by applying a set of well-established scales and predictors of outcome and to compare efficacy between ziprasidone and haloperidol. Methods One hundred twelve schizophrenia patients (ziprasidone: n=54; haloperidol: n=58) were rated weekly on the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the Global Assessment of Functioning Scale (GAF), the Social and Occupational Functioning Scale (SOFAS), the Simpson-Angus Scale (SAS), and Hillside Akathisia Scale (HAS). Results Ninety-two patients (82%) were predicted to have a high risk of nonresponse. No significant difference regarding PANSS improvement in this subsample was found comparing ziprasidone and haloperidol (p=0.563). Also, for the total patient sample, no significant difference was found regarding the course of the PANSS total score, GAF (p=0.921), and SOFAS (p=0.658) between ziprasidone and haloperidol. Haloperidol resulted in higher scores on the SAS (p=0.001) and HAS (p=0.011). Discussion An alarmingly high number of patients were at high risk of nonresponse to antipsychotic treatment.

Significant changes of schizophrenia patients during inpatient treatment were evalutaed and compared to established outcome criteria. The concept of reliable and clinically significant change methods was applied to three hundred and ninety-six patients suffering from a schizophrenia spectrum disorder. First, information on whether or not the change of the patient's condition is sufficient in order to declare that it is beyond a measurement error or random effect (= reliable change) was evaluated and in a second step it was observed if the reliable change was clinically meaningful (= clinically significant change). Different Positive and Negative Syndrome Scale for Schizophrenia (PANSS) thresholds were applied to define the clinically significant change (40, 45 and 50 points). These changes were then compared to established outcome criteria such as response and remission. Seventy-nine of the 396 patients (20%) showed a reliable improvement of symptoms, whereas 70% improved without achieving a reliable change of their condition. Of the 79 patients achieving a reliable change during treatment 8-15% concurrently showed a clinically significant change depending on the respective PANSS threshold. In contrast, 56% of the patients achieved response and 60% were in remission at discharge when applying established outcome criteria. Our results showed that a rather small number of schizophrenia patients were found to reliably change during inpatient treatment, with even less patients achieving a clinically significant change. The concept of reliable and clinically significant changes revealed to be a lot more stringent than today's established outcome criteria and should be critically evaluated regarding its use in schizophrenia patients. Copyright (c) 2015 John Wiley-Blackwell & Sons, Ltd. Significant changes of schizophrenia patients during inpatient treatment were evalutaed and compared to established outcome criteria. The concept of reliable and clinically significant change methods was applied to three hundred and ninety-six patients suffering from a schizophrenia spectrum disorder. First, information on whether or not the change of the patient's condition is sufficient in order to declare that it is beyond a measurement error or random effect (=reliable change) was evaluated and in a second step it was observed if the reliable change was clinically meaningful (=clinically significant change). Different Positive and Negative Syndrome Scale for Schizophrenia (PANSS) thresholds were applied to define the clinically significant change (40, 45 and 50 points). These changes were then compared to established outcome criteria such as response and remission. Seventy-nine of the 396 patients (20%) showed a reliable improvement of symptoms, whereas 70% improved without achieving a reliable change of their condition. Of the 79 patients achieving a reliable change during treatment 8-15% concurrently showed a clinically significant change depending on the respective PANSS threshold. In contrast, 56% of the patients achieved response and 60% were in remission at discharge when applying established outcome criteria. Our results showed that a rather small number of schizophrenia patients were found to reliably change during inpatient treatment, with even less patients achieving a clinically significant change. The concept of reliable and clinically significant changes revealed to be a lot more stringent than today's established outcome criteria and should be critically evaluated regarding its use in schizophrenia patients.

Slipstream Slump, a well-preserved 3 km wide sedimentary failure from the frontal ridge of the Cascadia accretionary wedge 85 km off Vancouver Island, Canada, was sampled during Canadian Coast Guard Ship (CCGS) John P. Tully cruise 2008007PGC along a transect of five piston cores. Shipboard sediment analysis and physical property logging revealed 12 turbidites interbedded with thick hemipelagic sediments overlying the slumped glacial diamict. Despite the different sedimentary setting, atop the abyssal plain fan, this record is similar in number and age to the sequence of turbidites sampled farther to the south from channel systems along the Cascadia Subduction Zone, with no extra turbidites present in this local record. Given the regional physiographic and tectonic setting, megathrust earthquake shaking is the most likely trigger for both the initial slumping and subsequent turbidity currents, with sediments sourced exclusively from the exposed slump face of the frontal ridge. Planktonic foraminifera picked from the resedimented diamict of the underlying main slump have a disordered cluster of 14C ages between 12.8 and 14.5 ka BP. For the post-slump stratigraphy, an event-free depth scale is defined by removing the turbidite sediment intervals and using the hemipelagic sediments. Nine 14C dates from the most foraminifera-rich intervals define a nearly constant hemipelagic sedimentation rate of 0.021 cm/year. The combined age model is defined using only planktonic foraminiferal dates and Bayesian analysis with a Poisson-process sedimentation model. The age model of ongoing hemipelagic sedimentation is strengthened by physical property correlations from Slipstream events to the turbidites for the Barkley Canyon site 40 km south. Additional modelling addressed the possibilities of seabed erosion or loss and basal erosion beneath turbidites. Neither of these approaches achieves a modern seabed age when applying the commonly used regional marine 14C reservoir age of 800 years (marine reservoir correction ΔR = 400 years). Rather, the top of the core appears to be 400 years in the future. A younger marine reservoir age of 400 years (ΔR = 0 years) brings the top to the present and produces better correlations with the nearby Effingham Inlet paleo-earthquake chronology based only on terrestrial carbon requiring no reservoir correction. The high-resolution dating and facies analysis of Slipstream Slump in this isolated slope basin setting demonstrates that this is also a useful type of sedimentary target for sampling the paleoseismic record in addition to the more studied turbidites from submarine canyon and channel systems. The first 10 turbidites at Slipstream Slump were deposited between 10.8 and 6.6 ka BP, after which the system became sediment starved and only two more turbidites were deposited. The recurrence interval for the inferred frequent early Holocene megathrust earthquakes is 460 ± 140 years, compatible with other estimates of paleoseismic megathrust earthquake occurrence rates along the subduction zone.

Highlights • Sediment influence on hydrate dissolution was studied in the field and lab • In the field, CH4(aq) concentrations were at or below theoretical saturation • Dissolution of natural hydrate blanketed by 15 cm thick sediment was measured • This covered hydrate dissolved at a slower rate than nearby exposed hydrates • In the lab, exposed hydrate dissolved faster than covered hydrate Abstract Dissolution rates of naturally occurring gas hydrates vary by orders of magnitude across studies suggesting that environmental factors may influence hydrate dissolution. To determine the role that sediment cover plays in hydrate dissolution, we used a mini-pore fluid array sampler (mPFA) to continuously collect sediment porewater adjacent to a hydrate outcrop and maintain it at in situ pressure for later analysis. This allowed us to measure in situ dissolved hydrocarbon concentrations in the porewater over time without sample loss due to degassing. We deployed the mPFA at a hydrate outcrop at Barkley Canyon on the Cascadia Margin for nine months. This novel approach yielded concentration data that were used to determine the steady-state dissolution rate of the hydrate outcrop and test predictions of the diffusion-control model for dissolution in the field. In the lab, we conducted a series of experiments with artificial hydrate to directly compare dissolution rates between exposed and sediment-covered hydrate. The dissolution rate of the natural hydrate outcrop covered with sediment was 0.06 cm y− 1. The laboratory experiments of sediment-covered hydrate yielded dissolution rates of 0.6 ± 0.5 cm y− 1 (n = 5). In both laboratory and field observations, the dissolution rate of hydrates exposed directly to bulk water (3.9 ± 1.7 cm y− 1 and 3.5 cm y− 1 respectively) was at least an order of magnitude faster than the dissolution rate of sediment covered hydrate. These results are consistent with expectations of diffusion-control and support this model of hydrate dissolution. In nature, sediment may account for the persistence of hydrate in otherwise methane-depleted environments by increasing the diffusive boundary layer and slowing the rate of molecular diffusion via porosity/tortuosity effects. We provide a number of “Lessons Learned” for improving the instrument design and for consideration during future studies.

The 2012 Mw 7.8 Haida Gwaii earthquake confirmed very oblique subduction and slip partitioning at the southern Queen Charlotte margin. In this study, we re‐examine the thermal regime near the earthquake using new model constraints and with the recognition that hydrothermal circulation in the subducting oceanic crust can significantly affect the margin thermal regime. The observed heat flow values are extremely high just seaward of the trench but decrease rapidly landward. We explain this pattern as the consequence of very vigorous hydrothermal circulation in the subducting oceanic crust. Using a finite‐element model, we simulate the thermal effect of the circulation using a high‐conductivity proxy that represents a very high Nusselt number in an aquifer along the top of the oceanic plate. Our thermal model indicates that the temperature at the intersection of the megathrust and the strike‐slip Queen Charlotte fault (QCF) just seaward of the coast is about 350° C, approximately the limit of seismogenic behavior, and cooler than previous models that did not include hydrothermal circulation. The change of plate motion kinematics across the QCF approximately coincides with a down‐dip transition of the thermally controlled seismogenic behavior of the megathrust. Seaward of the QCF, the shallow megathrust accommodates mainly the margin‐normal component of relative plate motion, with the strike‐slip component accommodated by the QCF. This portion of the megathrust exhibits stick slip and produced the 2012 Haida Gwaii earthquake. Landward of the QCF, the megathrust fully accommodates the very oblique motion of the oceanic plate beneath the continental crust and exhibits creep.

High-resolution multibeam bathymetry data collected with an autonomous underwater vehicle (AUV) complemented by compressed high-intensity radar pulse (Chirp) profiles and remotely operated vehicle (ROV) observations and sediment sampling reveal a distinctive rough topography associated with seafloor gas venting and/or near-subsurface gas hydrate accumulations. The surveys provide 1 m bathymetric grids of deep-water gas venting sites along the best-known gas venting areas along the Pacific margin of North America, which is an unprecedented level of resolution. Patches of conspicuously rough seafloor that are tens of meters to hundreds of meters across and occur on larger seafloor topographic highs characterize seepage areas. Some patches are composed of multiple depressions that range from 1 to 100 m in diameter and are commonly up to 10 m deeper than the adjacent seafloor. Elevated mounds with relief of >10 m and fractured surfaces suggest that seafloor expansion also occurs. Ground truth observations show that these areas contain broken pavements of methane-derived authigenic carbonates with intervening topographic lows. Patterns seen in Chirp profiles, ROV observations, and core data suggest that the rough topography is produced by a combination of diagenetic alteration, focused erosion, and inflation of the seafloor. This characteristic texture allows previously unknown gas venting areas to be identified within these surveys. A conceptual model for the evolution of these features suggests that these morphologies develop slowly over protracted periods of slow seepage and shows the impact of gas venting and gas hydrate development on the seafloor morphology.

To assess daytime cognitive performance, sedation and treatment satisfaction in patients with schizophrenia receiving quetiapine extended release (XR) versus quetiapine immediate release (IR).Phase IV prospective, double-blind, crossover study (NCT01213836). Patients (N=66) with stable schizophrenia, treated with XR or IR before study start, were randomised (1:1) to treatment with XR followed by IR, or IR followed by XR, at the dose received before enrolment (400-750mg). After 10-16days on formulation 1, patients switched to formulation 2. Assessments from three post-dose visits (≥5days following treatment on each formulation) were analysed. Cognitive performance was measured by CogState Cognition testing. Sedation, treatment satisfaction and safety were also assessed.65 patients received treatment (69.2% male; mean age 37.8years). Daytime cognitive functioning was similar for both groups; adjusted mean difference in Attentional Composite Score in XR and IR patients was 0.005 (p=0.907). Patients receiving XR were less sedated than those receiving IR, (Bond-Lader visual analogue scale score, mean [SD]: 23.5 [19.0] vs 28.6 [21.4]); estimated overall treatment difference: 5.2 (95% CI: 2.3, 8.2; p0.0009). Patients receiving XR reported feeling less sedated than those on IR (Stanford Sleepiness Scale, mean [SD]: 2.4 [0.9] vs 2.6 [1.0]); estimated overall treatment difference: 0.28 (95% CI: 0.12, 0.43; p0.0008). Patients reported improved overall treatment satisfaction (p=0.0417) and milder side effects (p=0.0035) with XR. Safety profile was similar in both groups.Daytime cognitive performance was similar for both groups. XR was associated with less daytime sedation and improved patient satisfaction than IR.

How long clinicians should wait before considering an antipsychotic ineffective and changing treatment in schizophrenia is an unresolved clinical question. Guidelines differ substantially in this regard. The authors conducted a diagnostic test meta-analysis using mostly individual patient data to assess whether lack of improvement at week 2 predicts later nonresponse. The search included EMBASE, MEDLINE, BIOSIS, PsycINFO, Cochrane Library, CINAHL, and reference lists of relevant articles, supplemented by requests to authors of all relevant studies. The main outcome was prediction of nonresponse, defined as

Gas hydrate resource assessments that indicate enormous global volumes of gas present within hydrate accumulations have been one of the primary driving forces behind the growing interest in gas hydrates. Gas hydrate volumetric estimates in recent years have focused on documenting the geologic parameters in the “gas hydrate petroleum system” that control the occurrence of gas hydrates in nature. The primary goals of this report are to review our present understanding of the geologic controls on the occurrence of gas hydrate in the offshore of India and to document the application of the petroleum system approach to the study of gas hydrates. National Gas Hydrate Program of India executed the National Gas Hydrate Program Expedition 01 (NGHP-01) in 2006 in four areas located on the eastern and western margins of the Indian Peninsula and in the Andaman Sea. These areas have experienced very different tectonic and depositional histories. The peninsular margins are passive continental margins resulting from a series of rifting episodes during the breakup and dispersion of Gondwanaland to form the present Indian Ocean. The Andaman Sea is bounded on its western side by a convergent margin where the Indian plate lithosphere is being subducted beneath southeast Asia. NGHP-01 drilled, logged, and/or cored 15 sites (31 holes) in the Krishna–Godavari Basin, 4 sites (5 holes) in the Mahanadi Basin, 1 site (2 holes) in the Andaman Sea, and 1 site (1 hole) in the Kerala–Konkan Basin. Holes were drilled using standard drilling methods for the purpose of logging-while-drilling and dedicated wireline logging; as well as through the use of a variety of standard coring systems and specialized pressure coring systems. NGHP-01 yielded evidence of gas hydrate from downhole log and core data obtained from all the sites in the Krishna–Godavari Basin, the Mahanadi Basin, and in the Andaman Sea. The site drilled in the Kerala–Konkan Basin during NGHP-01 did not yield any evidence of gas hydrate. Most of the downhole log-inferred gas hydrate and core-recovered gas hydrate were characterized as either fracture-filling in clay-dominated sediments or as pore-filling or grain-displacement particles disseminated in both fine- and coarse-grained sediments. Geochemical analyses of gases obtained from sediment cores recovered during NGHP-01 indicated that the gas in most all of the hydrates in the offshore of India is derived from microbial sources; only one site in the Andaman Sea exhibited limited evidence of a thermogenic gas source. The gas hydrate petroleum system concept has been used to effectively characterize the geologic controls on the occurrence of gas hydrates in the offshore of India.

Shear wave velocity data have been acquired at several marine gas hydrate drilling expeditions, including the India National Gas Hydrate Program Expedition 1 (NGHP-01), the Ocean Drilling Program (ODP) Leg 204, and Integrated Ocean Drilling Program (IODP) Expedition 311 (X311). In this study we use data from these marine drilling expeditions to develop an understanding of general grain-size control on the P- and S-wave properties of sediments. A clear difference in the downhole trends of P-wave (Vp) and S-wave (Vs) velocity and the Vp/Vs ratio from all three marine regions was observed: the northern Cascadia margin (IODP X311) shows the highest P-wave and S-wave velocity values overall and those from the India margin (Expedition NGHP-01) are the lowest. The southern Cascadia margin (ODP Leg 204) appears to have similar low P-wave and S-wave velocity values as seen off India. S-wave velocity values increase relative to the sites off India, but they are not as high as those seen on the northern Cascadia margin. Such regional differences can be explained by the amount of silt/sand (or lack thereof) occurring at these sites, with northern Cascadia being the region of the highest silt/sand occurrences. This grain-size control on P-wave and S-wave velocity and associated mineral composition differences is amplified when compared to the Arctic permafrost environments, where gas hydrate predominantly occurs in sand- and silt-dominated formations. Using a cross-plot of gamma ray values versus the Vp/Vs ratio, we compare the marine gas hydrate occurrences in these regions: offshore eastern India margin, offshore Cascadia margin, the Ignik-Sikumi site in Alaska, and the Mallik 5L-38 site in the Mackenzie Delta. The log-data from the Arctic permafrost regions show a strongly linear Vp–Vs relationship, similar to the previously defined empirical relationships by Greenberg and Castagna (1992). P- and S-wave velocity data from the India margin and ODP Leg 204 deviate strongly from these linear trends, whereas data from IODP X311 plot closer to the trend of the Arctic data sets and previously published relationships. Three new linear relationships for different grain size marine sediment hosts are suggested: a) mud-dominated (Mahanadi Basin, ODP Leg 204 & NGHP-01-17): Vs = 1.5854 × Vp − 2.1649 b) silty-mud (KG Basin): Vs = 0.8105 × Vp − 1.0223 c) silty-sand (IODP X311): Vs = 0.5316 × Vp − 0.4916 We investigate the relationship of gas hydrate saturation determined from electrical resistivity on the Vp/Vs ratio and found that the sand-dominated Arctic hosts show a clearly decreasing trend of Vp/Vs ratio with gas hydrate saturation. Though limited due to lower overall GH saturations, a similar trend is seen for sites from IODP X311 and at the ash-dominated NGHP-01-17 sediment in the Andaman Sea. Gas hydrate that occurs predominantly in fractured clay hosts show a different trend where the Vp/Vs ratio is much higher than at sand-dominated sites and remains constant or increases slightly with increasing gas hydrate saturation. This trend may be the result of anisotropy in fracture-dominated systems, where P- and S-wave velocities appear higher and Archie-based saturations of gas hydrate are overestimated. Gas hydrate concentrations were also estimated in these three marine settings and at Arctic sites using an effective medium model, combining P- and S-wave velocities as equally weighted constraints on the calculation. The effective medium approach generally overestimates S-wave velocity in high-porosity, clay-dominated sediments, but can be accurately used in sand-rich formations.

Gas hydrate was recovered in the Mahanadi Basin along the eastern continental margin of India during the India National Gas Hydrate Program (NGHP) Expedition-01 in 2006. Infrared imaging of recovered core confirmed gas hydrate occurs predominantly in discrete layers. Pore-water chemistry, electrical resistivity and acoustic velocity down-hole logs were used to estimate gas hydrate saturations at three of the sites in the Mahanadi Basin: Sites NGHP-01-08, -09, and -19. Gas hydrate saturation estimated from pore-water chloride concentrations shows values up to ∼10% of the pore space at ∼200 m below seafloor just above the base of the gas hydrate stability zone (BGHSZ). Gas hydrate saturations estimated from electrical resistivity and acoustic velocity logs using standard relations and modeling approaches are comparable to each other and saturations are ∼10–15% of the pore space. Seismic reflection data were also analyzed for the evidence of gas hydrate, and a bottom-simulating reflector (BSR) was imaged along the seismic profiles in the study area. The depth of the BSR is varying from ∼200 m to ∼300 m below seafloor depending on water depth in the Mahanadi Basin. The occurrence of gas hydrate was observed to be associated with deep-water channel and levee complexes (especially at Site NGHP-01-19) based on the regional seismic data. But the cored/logged section at each site lacked any significant sand fraction, which does not allow for higher gas hydrate saturations. As identified from seismic time-slice data, all sites drilled in the Mahanadi Basin are within the steeper slope region of the channel system and any sand bypassed this region. Significant sand deposition would occur further down slope where typical fan-type deposits can be inferred from the seismic data and thus higher accumulations of gas hydrate would be expected.

Offshore seismicity at the Cascadia margin is poorly constrained because nearly all previous recordings of earthquakes were made using land‐based networks. We conducted earthquake monitoring off Vancouver Island in northern Cascadia using ocean‐bottom seismographs. Our results show that most of the offshore seismicity is concentrated along the Nootka fault zone. Otherwise seismicity is extremely low, with no earthquakes located along the shallow, seismogenic part of the megathrust. The lack of interplate seismicity may indicate complete healing and locking of the megathrust over three centuries after the great earthquake of 1700 and a somewhat lower degree of structure heterogeneity, such as subducting seamounts. Events along the Nootka fault zone occur over a 10–15 km depth range. This wide distribution and the previously reported overall moment release rate suggest that a significant part of deformation of this fault zone is aseismic. Several earthquakes beneath the continental shelf may be related to faults dividing tectonic terrains within the overriding plate.

Subtyping depression is important in order to further delineate biological causes of depressive syndromes. The aim of this study was to evaluate clinical and outcome characteristics of distinct subtypes of depression and to assess proportion and features of patients fulfilling criteria for more than one subtype. Melancholic, atypical and anxious subtypes of depression were assessed in a naturalistic sample of 833 inpatients using DSM-IV specifiers based on operationalized criteria. Baseline characteristics and outcome criteria at discharge were compared between distinct subtypes and their overlap. A substantial proportion of patients (16%) were classified with more than one subtype of depression, 28% were of the distinct anxious, 7% of the distinct atypical and 5% of the distinct melancholic subtype. Distinct melancholic patients had shortest duration of episode, highest baseline depression severity, but were more often early improvers; distinct anxious patients had higher NEO-Five Factor Inventory (NEO-FFI) neuroticism scores compared with patients with unspecific subtype. Melancholic patients with overlap of anxious features had worse treatment outcome compared to distinct melancholic and distinct anxious subtype. Distinct subtypes differed in only few variables and patients with overlap of depression subtypes may have independent clinical and outcome characteristics. Studies investigating biological causes of subtypes of depression should take influence of features of other subtypes into account.

Background Signs of an inflammatory process have been described in major depression. Methods In a double-blind, randomized study of celecoxib or placebo add-on to reboxetine in 40 depressed patients, celecoxib treatment has beneficial effects. In order to evaluate the tryptophan/kynurenine metabolism and to identify predictors for remission, tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QUIN) were estimated in the serum of 32 patients before and after treatment and in a group of 20 healthy controls. Results KYN levels were significantly lower in patients (p = 0.008), and the QUIN/KYN ratios were significantly higher (p = 0.028). At baseline, the higher KYN/TRP ratio was predictive for remission during celecoxib add-on treatment (p = 0.04) as well as for remission in the overall patient group (p = 0.01). In the placebo group, remitters showed a higher KYNA/QUIN ratio (p = 0.032). In the overall group, remitters showed lower KYNA/KYN (p = 0.035) and QUIN/KYN (p = 0.011) ratios. The lower the formation of downstream metabolites, especially QUIN, the better the treatment outcome. Conclusion The high KYN/TRP ratio predicted remission after treatment with celecoxib in this small sample of depressed patients. Eventually, the KYN/TRP ratio might be a marker for those patients, which benefit from an additional anti-inflammatory treatment.

Alignments of fractures and cracks in marine sediments may be controlled by various mechanisms such as horizontal compaction and extension and basement faulting. The orientation of these alignments can be estimated through analyses of S‐wave splitting. If sensors in ocean‐bottom observations are deployed through free fall, sensor orientation needs to be determined in order for the recorded data to be used for such analyses. Here, we estimate the sensor orientation from the linear particle motions of P‐to‐s (Ps) phases converted at the sediment–basement interface and also from T waves that are excited by earthquakes and propagate in the seawater. We examine waveforms of local earthquakes recorded by 32 ocean‐bottom seismometers (OBSs) that were deployed through free fall for three months in 2010 off Vancouver Island where the strike‐slip Nootka fault zone (NFZ) intersects the deformation front of the Cascadia subduction zone. Because the particle motion of the Ps wave was corrected by estimating splitting parameters, the fast polarization direction, which reflects S‐wave anisotropic structure within the sediment, can also be evaluated. Consequently, we could estimate the fast polarization direction at OBSs deployed near the NFZ and west of the deformation front. The obtained fast directions appeared to correspond to alignments of shear fractures in the marine sediments associated with the left‐lateral motion of the fault in the basement along the NFZ, margin‐normal cracks due to horizontal compression west of and slightly away from the deformation front, and frontal thrust faults within the accretionary prism near the deformation front.