Improvements in Circumpolar Southern Hemisphere Extratropical Atmospheric Circulation in CMIP6 Compared to CMIP5

One of the major globally relevant systematic biases in previous generations of climate models has been an equatorward bias in the latitude of the Southern Hemisphere (SH) mid‐latitude tropospheric eddy driven westerly jet. The far reaching implications of this for Southern Ocean heat and carbon uptake and Antarctic land and sea ice are key reasons why addressing this bias is a high priority. It is therefore of primary importance to evaluate the representation of the SH westerly jet in the latest generation of global climate and earth‐system models that comprise the Coupled Model Intercomparison Project Phase 6 (CMIP6). In this paper we assess the representation of major indices of SH extratropical atmospheric circulation in CMIP6 by comparison against both observations and the previous generation of CMIP5 models. Indices assessed are the latitude and speed of the westerly jet, variability of the Southern Annular Mode (SAM) and representation of the Amundsen Sea Low (ASL). These are calculated from the historical forcing simulations of both CMIP5 and CMIP6 for time periods matching available observational and reanalysis datasets. From the 39 CMIP6 models available at the time of writing there is an overall reduction in the equatorward bias of the annual mean westerly jet from 1.9° in CMIP5 to 0.4° in CMIP6 and from a seasonal perspective the reduction is clearest in austral spring and summer. This is accompanied by a halving of the bias of SAM decorrelation timescales compared to CMIP5. However, no such overall improvements are evident for the ASL

Acute inhibition of MEK suppresses congenital melanocytic nevus syndrome in a murine model driven by activated NRAS and Wnt signaling

Congenital melanocytic nevus (CMN) syndrome is the association of pigmented melanocytic nevi with extra-cutaneous features, classically melanotic cells within the central nervous system, most frequently caused by a mutation of NRAS codon 61. This condition is currently untreatable and carries a significant risk of melanoma within the skin, brain, or leptomeninges. We have previously proposed a key role for Wnt signaling in the formation of melanocytic nevi, suggesting that activated Wnt signaling may be synergistic with activated NRAS in the pathogenesis of CMN syndrome. Some familial pre-disposition suggests a germ-line contribution to CMN syndrome, as does variability of neurological phenotypes in individuals with similar cutaneous phenotypes. Accordingly, we performed exome sequencing of germ-line DNA from patients with CMN to reveal rare or undescribed Wnt-signaling alterations. A murine model harboring activated NRASQ61K and Wnt signaling in melanocytes exhibited striking features of CMN syndrome, in particular neurological involvement. In the first model of treatment for this condition, these congenital, and previously assumed permanent, features were profoundly suppressed by acute post-natal treatment with a MEK inhibitor. These data suggest that activated NRAS and aberrant Wnt signaling conspire to drive CMN syndrome. Post-natal MEK inhibition is a potential candidate therapy for patients with this debilitating condition

Understanding Late Quaternary change at the land ocean interface: a synthesis of the evolution of the Wilderness coastline, South Africa

Coastal barrier systems have been widely used to understand the responses of coastal margins to fluctuating Pleistocene sea levels. What has become apparent, particularly with the development of robust chronological frameworks, is that gaps in terrestrial barrier sedimentary records are not uncommon and that they most likely reflect phases of barrier construction on the now submerged continental shelf. Thus, understanding the land–ocean interface through time is critical to fully appreciate the Quaternary archives contained within the barriers and their associated back-barrier deposits. This study uses offshore and lakefloor (back-barrier) seismic profiling from the South African south coast at Wilderness to link the sub-aerially exposed barrier stratigraphy to the currently submerged geological and sedimentological record. A total of eight separate submerged aeolian units are identified at water depths of up to 130 m below mean sea level. Their approximate ages are constrained with reference to the eustatic sea-level record and the deepest units are consistent with the estimated magnitude of sea-level lowering during the Last Glacial Maximum (LGM) on the South African coastline. As previously assumed, aeolian sedimentation tracked the shoreline onto the continental shelf during the Late Pleistocene. During sea-level regressions, both the incision of fluvial channels and the deposition of back-barrier systems occurred across the continental shelf. During late low stand/early transgression periods, landward shoreface migration occurred, pre-existing channel incisions were infilled and pre-existing barriers were truncated. Rapid transgression, however, allowed the preservation of some back-barrier deposits, possibly aided by protection from antecedent topography. As sea level neared the present-day elevation, erosion of the mid-shelf sediments resulted in the development of a Holocene sediment wedge, which was augmented by Holocene fluvial sediment supply. The Holocene sand wedge is preserved in the back-barrier lakes and was deposited during the Holocene highstand inundation. Overlying middle to late Holocene terrestrial muds reflect the deposition of river-borne mud onto the shelf. These results clearly demonstrate that within transgressive–regressive sea-level cycles, accommodation space for barriers is controlled by antecedent drainage systems and gradients on the adjacent inner continental shelf

The computational fluid dynamics modelling of the autorotation of square, flat plates

This paper examines the use of a coupled Computational Fluid Dynamics (CFD) – Rigid Body Dynamics (RBD) model to study the fixed-axis autorotation of a square flat plate. The calibration of the model against existing wind tunnel data is described. During the calibration, the CFD models were able to identify complex period autoration rates, which were attributable to a mass eccentricity in the experimental plate. The predicted flow fields around the autorotating plates are found to be consistent with existing observations. In addition, the pressure coefficients from the wind tunnel and computational work were found to be in good agreement. By comparing these pressure distributions and the vortex shedding patterns at various stages through an autorotation cycle, it was possible to gain important insights into the flow structures that evolve around the plate. The CFD model is also compared against existing correlation functions that relate the mean tip speed ratio of the plate to the aspect ratio, thickness ratio and mass moment of inertia of the plate. Agreement is found to be good for aspect ratios of 1, but poor away from this value. However, other aspects of the numerical modelling are consistent with the correlations

A systematic review and meta-analysis of the effect of cognitive interventions to prevent intrusive memories using the trauma film paradigm

There is an unmet need for effective early interventions that can relieve initial trauma symptoms and reduce symptoms of posttraumatic stress disorder (PTSD). We evaluated the efficacy of cognitive interventions compared to control in reducing intrusion frequency and PTSD symptoms in healthy individuals using the trauma film paradigm, in which participants view a film with aversive content as an experimental analogue of trauma exposure. A systematic literature search identified 41 experiments of different cognitive interventions targeting intrusions. In the meta-analysis, the pooled effect size of 52 comparisons comparing cognitive interventions to no-intervention controls on intrusions was moderate (g = −0.46, 95% CI [–0.61 to −0.32], p < .001). The pooled effect size of 16 comparisons on PTSD symptoms was also moderate (g = −0.31, 95% CI [–0.46 to −0.17], p < .001). Both visuospatial interference and imagery rescripting tasks were associated with significantly fewer intrusions than controls, whereas verbal interference and meta-cognitive processing tasks showed nonsignificant effect sizes. Interventions administered after viewing the trauma film showed significantly fewer intrusions than controls, whereas interventions administered during film viewing did not. No experiments had low risk of bias (ROB), 37 experiments had some concerns of ROB, while the remaining four experiments had high ROB. To the best of our knowledge, this is the first meta-analysis investigating the efficacy of cognitive interventions targeting intrusions in non-clinical samples. Results seem to be in favour of visuospatial interference tasks rather than verbal tasks. More research is needed to develop an evidence base on the efficacy of various cognitive interventions and test their clinical translation to reduce intrusive memories of real trauma

Functional diversity of chemokines and chemokine receptors in response to viral infection of the central nervous system.

Encounters with neurotropic viruses result in varied outcomes ranging from encephalitis, paralytic poliomyelitis or other serious consequences to relatively benign infection. One of the principal factors that control the outcome of infection is the localized tissue response and subsequent immune response directed against the invading toxic agent. It is the role of the immune system to contain and control the spread of virus infection in the central nervous system (CNS), and paradoxically, this response may also be pathologic. Chemokines are potent proinflammatory molecules whose expression within virally infected tissues is often associated with protection and/or pathology which correlates with migration and accumulation of immune cells. Indeed, studies with a neurotropic murine coronavirus, mouse hepatitis virus (MHV), have provided important insight into the functional roles of chemokines and chemokine receptors in participating in various aspects of host defense as well as disease development within the CNS. This chapter will highlight recent discoveries that have provided insight into the diverse biologic roles of chemokines and their receptors in coordinating immune responses following viral infection of the CNS

A microflow cytometer for microsphere-based immunoassays using integrated optics and inertial particle focussing

We present work towards a microflow cytometer for performing multiplex immunoassays using commercially available fluorescently-labelled microspheres. The device consists of a silica chip with integrated GeO2:SiO2 channel waveguides which deliver excitation light orthogonally to an etched flow channel [1], [2]. The rectangular cross section, 2:1 aspect ratio flow channel and flow rate create an inertial focussing effect on the microspheres [3] which ensures they flow through the plane of maximum optical excitation, halfway up the height of the channel, with minimal positional variation. The optical waveguide core is fabricated by magnetron sputtering of GeO2:SiO2 films which are then etched to form channel waveguides by ICP etching. The silica cladding, up to 13.5 µm thick, is deposited by either flame hydrolysis deposition or a combination of magnetron sputtering followed by PECVD. Fluidic channels are etched with ICP etching. Channels with the dimensions of 14.1 µm x 27.5 µm and near vertical sidewalls (91°±4°) have been produced in silica as shown in the cross section in Figure 1A. Figure 1B shows a device with the fluidic channel etched through waveguides clad with PECVD silica. Design parameters were established with PDMS test channels 25.5 µm deep by 12.2 µm wide. Figures 2A and 2B show transmission fluorescence imaging of streaks from multiple 5.6µm diameter microspheres flowing at 0.49 m/s down the fluidic channel. The microspheres are shown to be focused into a tight stream at 15 mm from the channel entrance in Figure 2C, indicating the minimum channel length required for the final devices. Future work will include dual channel quantification of microsphere fluorescence and development of an assay for TNFalpha and later multiplex measurements. Collection of fluorescence with channel waveguides and also characterisation of transmission measurements from flowing microspheres will also be studied

The Suicidal Intrusions Attributes Scale (SINAS): a new tool measuring suicidal intrusions

Introduction: Suicidal intrusions are uncontrollable, intrusive mental images (e. g., visualizing a future suicidal act). They may also be called suicidal “flash-forwards.” Despite the importance of integrating the assessment of suicidal intrusions into a clinical routine assessment, quick self-report screening instruments are lacking. This study describes the development of a new instrument—Suicidal Intrusions Attributes Scale (SINAS)—to assess the severity and characteristics of suicidal intrusions and examines its psychometric properties. Method: The sample included currently suicidal outpatients with elevated levels of depression recruited across mental health institutions in the Netherlands (N = 168). Instruments administered were 10-item SINAS, the Suicidal Ideation Attributes Scale (SIDAS), the Prospective Imagery Task (PIT), four-item Suicidal Cognitions Interview (SCI), and the Beck Depression Inventory (BDI-II). Results: An exploratory factor analysis identified a one-factor structure. The resulting SINAS demonstrated good internal consistency (Cronbach's α = 0.91) and convergent validity, as expected. Discussion: Overall, this study demonstrated acceptable levels of reliability and validity of the measure in a depressed clinical population with suicidal ideation. The SINAS may be a useful screening tool for suicidal intrusions in both research and clinical settings

Ecological Invasion, Roughened Fronts, and a Competitor's Extreme Advance: Integrating Stochastic Spatial-Growth Models

Both community ecology and conservation biology seek further understanding of factors governing the advance of an invasive species. We model biological invasion as an individual-based, stochastic process on a two-dimensional landscape. An ecologically superior invader and a resident species compete for space preemptively. Our general model includes the basic contact process and a variant of the Eden model as special cases. We employ the concept of a "roughened" front to quantify effects of discreteness and stochasticity on invasion; we emphasize the probability distribution of the front-runner's relative position. That is, we analyze the location of the most advanced invader as the extreme deviation about the front's mean position. We find that a class of models with different assumptions about neighborhood interactions exhibit universal characteristics. That is, key features of the invasion dynamics span a class of models, independently of locally detailed demographic rules. Our results integrate theories of invasive spatial growth and generate novel hypotheses linking habitat or landscape size (length of the invading front) to invasion velocity, and to the relative position of the most advanced invader.Comment: The original publication is available at www.springerlink.com/content/8528v8563r7u2742