The evolution of intracranial aneurysm treatment techniques and future directions.

Treatment techniques and management guidelines for intracranial aneurysms (IAs) have been continually developing and this rapid development has altered treatment decision-making for clinicians. IAs are treated in one of two ways: surgical treatments such as microsurgical clipping with or without bypass techniques, and endovascular methods such as coiling, balloon- or stent-assisted coiling, or intravascular flow diversion and intrasaccular flow disruption. In certain cases, a single approach may be inadequate in completely resolving the IA and successful treatment requires a combination of microsurgical and endovascular techniques, such as in complex aneurysms. The treatment option should be considered based on factors such as age; past medical history; comorbidities; patient preference; aneurysm characteristics such as location, morphology, and size; and finally the operator's experience. The purpose of this review is to provide practicing neurosurgeons with a summary of the techniques available, and to aid decision-making by highlighting ideal or less ideal cases for a given technique. Next, we illustrate the evolution of techniques to overcome the shortfalls of preceding techniques. At the outset, we emphasize that this decision-making process is dynamic and will be directed by current best scientific evidence, and future technological advances

Spatio-temporal patterns in the coral reef communities of the Spermonde Archipelago, 2012–2014, II: Fish assemblages display structured variation related to benthic condition

The Spermonde Archipelago is a complex of ~70 mostly populated islands off Southwest Sulawesi, Indonesia, in the center of the Coral Triangle. The reefs in this area are exposed to a high level of anthropogenic disturbances. Previous studies have shown that variation in the benthos is strongly linked to water quality and distance from the mainland. However, little is known about the fish assemblages of the region and if their community structure also follows a relationship with benthic structure and distance from shore. In this study, we used eight islands of the archipelago, varying in distance from 1 to 55 km relative to the mainland, and 3 years of surveys, to describe benthic and fish assemblages and to examine the spatial and temporal influence of benthic composition on the structure of the fish assemblages. Cluster analysis indicated that distinct groups of fish were associated with distance, while few species were present across the entire range of sites. Relating fish communities to benthic composition using a multivariate generalized linear model confirmed that fish groups relate to structural complexity (rugosity) or differing benthic groups; either algae, reef builders (coral and crustose coralline algae) or invertebrates and rubble. From these relationships we can identify sets of fish species that may be lost given continued degradation of the Spermonde reefs. Lastly, the incorporation of water quality, benthic and fish indices indicates that local coral reefs responded positively after an acute disturbance in 2013 with increases in reef builders and fish diversity over relatively short (1 year) time frames. This study contributes an important, missing component (fish community structure) to the growing literature on the Spermonde Archipelago, a system that features environmental pressures common in the greater Southeast Asian region

Spatio-temporal patterns in coral reef communities of the Spermonde Archipelago, 2012-2014, I: Comprehensive reef monitoring of water and benthic indicators reflect changes in reef health

Pollution, fishing, and outbreaks of predators can heavily impact coastal coral reef ecosystems, leading to decreased water quality and benthic community shifts. To determine the main environmental drivers of coral reef status in the Spermonde Archipelago, Indonesia, we monitored environmental variables and coral reef benthic community structure along an on-to-offshore gradient annually from 2012 to 2014. Findings revealed that concentrations of phosphate, chlorophyll a-like fluorescence, suspended particulate matter, and light attenuation significantly decreased from on-to-offshore, while concentrations of dissolved O2 and values of water pH significantly increased on-to-offshore. Nitrogen stable isotope signatures of sediment and an exemplary common brown alga were significantly enriched nearshore, identifying wastewater input from the city of Makassar as primary N source. In contrast to the high temporal variability in water quality, coral reef benthic community cover did not show strong temporal, but rather, spatial patterns. Turf algae was the dominant group next to live coral, and was negatively correlated to live coral, crustose coralline algae (CCA), rubble and hard substrate. Variation in benthic cover along the gradient was explained by water quality variables linked to trophic status and physico-chemical variables. As an integrated measure of reef status and structural complexity, the benthic index, based on the ratio of relative cover of live coral and CCA to other coral reef organisms, and reef rugosity were determined. The benthic index was consistently low nearshore and increased offshore, with high variability in the midshelf sites across years. Reef rugosity was also lowest nearshore and increased further offshore. Both indices dropped in 2013, increasing again in 2014, indicating a period of acute disturbance and recovery within the study and suggesting that the mid-shelf reefs are more resilient to disturbance than nearshore reefs. We thus recommend using these two indices with a selected number of environmental variables as an integral part of future reef monitoring

Comparison of Blister Aneurysm Treatment Techniques: A Systematic Review and Meta-Analysis

Objective Blood blister aneurysms are small, thin-walled, rapidly growing side-wall aneurysms that have proven particularly difficult to treat, and evidence-based guidance for treatment strategies is lacking. A systematic review and meta-analysis was performed to aggregate the available data and compare the three primary treatment modalities. Methods We performed a comprehensive literature search according to PRISMA guidelines followed by an indirect meta-analysis that compares the safety and efficacy of surgical, flow-diverting stents (FDS), and other endovascular approaches for the treatment of ruptured blood blister aneurysms. Results A total of 102 studies were included for quantitative synthesis with sample sizes of 687 treated surgically, 704 treated endovascularly without FDS, and 125 treated via flow-diversion. Comparatively, FDS achieved significantly reduced rates of perioperative retreatment compared to both surgical (P=0.025) and non-FDS endovascular (P<0.001). The FDS subgroup also achieved a significantly lower incidence of perioperative rebleed (P<0.001), perioperative hydrocephalus (P=0.012), postoperative infarction (P=0.002), postoperative hydrocephalus (P<0.001), and postoperative vasospasm (P=0.002) when compared to those patients in the open surgical subgroup. While no significant differences were found between groups on the basis of functional outcomes, angiographic outcomes detailed by rates of radiographic complete occlusion were highest for surgical (90.7%, 262/289) and FDS (89.1%, 98/110) subgroups versus the non-FDS endovascular subgroup at (82.7%, 268/324). Conclusion Flow-diversion appears to be an effective treatment strategy for ruptured BBAs with lower rates of perioperative complications when compared to surgical and other endovascular techniques but studies investigating long-term outcomes following flow-diversion warrant further study

Development of a Rabbit Human Glioblastoma Model for Testing of Endovascular Selective Intra-Arterial Infusion (ESIA) of Novel Stem Cell-Based Therapeutics

BACKGROUND: Endovascular selective intra-arterial (ESIA) infusion of cellular oncotherapeutics is a rapidly evolving strategy for treating glioblastoma. Evaluation of ESIA infusion requires a unique animal model. Our goal was to create a rabbit human GBM model to test IA infusions of cellular therapies and to test its usefulness by employing clinical-grade microcatheters and infusion methods to deliver mesenchymal stem cells loaded with an oncolytic adenovirus, Delta-24-RGD (MSC-D24). METHODS: Rabbits were immunosuppressed with mycophenolate mofetil, dexamethasone, and tacrolimus. They underwent stereotactic xenoimplantation of human GBM cell lines (U87, MDA-GSC-17, and MDA-GSC-8-11) into the right frontal lobe. Tumor formation was confirmed on magnetic resonance imaging, histologic, and immunohistochemistry analysis. Selective microcatheter infusion of MSC-D24 was performed via the ipsilateral internal carotid artery to assess model utility and the efficacy and safety of this approach. RESULTS: Twenty-five rabbits were implanted (18 with U87, 2 MDA-GSC-17, and 5 MDA-GSC-8-11). Tumors formed in 68% of rabbits (77.8% for U87, 50.0% for MDA-GSC-17, and 40.0% for MDA-GSC-8-11). On MRI, the tumors were hyperintense on T2-weighted image with variable enhancement (evidence of blood brain barrier breakdown). Histologically, tumors showed phenotypic traits of human GBM including varying levels of vascularity. ESIA infusion into the distal internal carotid artery of 2 ml of MSCs-D24 (107 cells) was safe in the model. Examination of post infusion specimens documented that MSCs-D24 homed to the implanted tumor at 24 hours. CONCLUSIONS: The intracranial immunosuppressed rabbit human GBM model allows testing of ESIA infusion of novel therapeutics (eg, MSC-D24) in a clinically relevant fashion

A hematopoietic contribution to microhemorrhage formation during antiviral CD8 T cell-initiated blood-brain barrier disruption

<p>Abstract</p> <p>Background</p> <p>The extent to which susceptibility to brain hemorrhage is derived from blood-derived factors or stromal tissue remains largely unknown. We have developed an inducible model of CD8 T cell-initiated blood-brain barrier (BBB) disruption using a variation of the Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis. This peptide-induced fatal syndrome (PIFS) model results in severe central nervous system (CNS) vascular permeability and death in the C57BL/6 mouse strain, but not in the 129 SvIm mouse strain, despite the two strains' having indistinguishable CD8 T-cell responses. Therefore, we hypothesize that hematopoietic factors contribute to susceptibility to brain hemorrhage, CNS vascular permeability and death following induction of PIFS.</p> <p>Methods</p> <p>PIFS was induced by intravenous injection of VP2_121-130peptide at 7 days post-TMEV infection. We then investigated brain inflammation, astrocyte activation, vascular permeability, functional deficit and microhemorrhage formation using T2*-weighted magnetic resonance imaging (MRI) in C57BL/6 and 129 SvIm mice. To investigate the contribution of hematopoietic cells in this model, hemorrhage-resistant 129 SvIm mice were reconstituted with C57BL/6 or autologous 129 SvIm bone marrow. Gadolinium-enhanced, T1-weighted MRI was used to visualize the extent of CNS vascular permeability after bone marrow transfer.</p> <p>Results</p> <p>C57BL/6 and 129 SvIm mice had similar inflammation in the CNS during acute infection. After administration of VP2_121-130peptide, however, C57BL/6 mice had increased astrocyte activation, CNS vascular permeability, microhemorrhage formation and functional deficits compared to 129 SvIm mice. The 129 SvIm mice reconstituted with C57BL/6 but not autologous bone marrow had increased microhemorrhage formation as measured by T2*-weighted MRI, exhibited a profound increase in CNS vascular permeability as measured by three-dimensional volumetric analysis of gadolinium-enhanced, T1-weighted MRI, and became moribund in this model system.</p> <p>Conclusion</p> <p>C57BL/6 mice are highly susceptible to microhemorrhage formation, severe CNS vascular permeability and morbidity compared to the 129 SvIm mouse. This susceptibility is transferable with the bone marrow compartment, demonstrating that hematopoietic factors are responsible for the onset of brain microhemorrhage and vascular permeability in immune-mediated fatal BBB disruption.</p

Induction of Blood Brain Barrier Tight Junction Protein Alterations by CD8 T Cells

Disruption of the blood brain barrier (BBB) is a hallmark feature of immune-mediated neurological disorders as diverse as viral hemorrhagic fevers, cerebral malaria and acute hemorrhagic leukoencephalitis. Although current models hypothesize that immune cells promote vascular permeability in human disease, the role CD8 T cells play in BBB breakdown remains poorly defined. Our laboratory has developed a novel murine model of CD8 T cell mediated central nervous system (CNS) vascular permeability using a variation of the Theiler's virus model of multiple sclerosis. In previous studies, we observed that MHC class II−/− (CD4 T cell deficient), IFN-γR−/−, TNF-α−/−, TNFR1−/−, TNFR2−/−, and TNFR1/TNFR2 double knockout mice as well as those with inhibition of IL-1 and LTβ activity were susceptible to CNS vascular permeability. Therefore, the objective of this study was to determine the extent immune effector proteins utilized by CD8 T cells, perforin and FasL, contributed to CNS vascular permeability. Using techniques such as fluorescent activated cell sorting (FACS), T1 gadolinium-enhanced magnetic resonance imaging (MRI), FITC-albumin leakage assays, microvessel isolation, western blotting and immunofluorescent microscopy, we show that in vivo stimulation of CNS infiltrating antigen-specific CD8 T cells initiates astrocyte activation, alteration of BBB tight junction proteins and increased CNS vascular permeability in a non-apoptotic manner. Using the aforementioned techniques, we found that despite having similar expansion of CD8 T cells in the brain as wildtype and Fas Ligand deficient animals, perforin deficient mice were resistant to tight junction alterations and CNS vascular permeability. To our knowledge, this study is the first to demonstrate that CNS infiltrating antigen-specific CD8 T cells have the capacity to initiate BBB tight junction disruption through a non-apoptotic perforin dependent mechanism and our model is one of few that are useful for studies in this field. These novel findings are highly relevant to the development of therapies designed to control immune mediated CNS vascular permeability

The Seventh Data Release of the Sloan Digital Sky Survey

This paper describes the Seventh Data Release of the Sloan Digital Sky Survey (SDSS), marking the completion of the original goals of the SDSS and the end of the phase known as SDSS-II. It includes 11663 deg^2 of imaging data, with most of the roughly 2000 deg^2 increment over the previous data release lying in regions of low Galactic latitude. The catalog contains five-band photometry for 357 million distinct objects. The survey also includes repeat photometry over 250 deg^2 along the Celestial Equator in the Southern Galactic Cap. A coaddition of these data goes roughly two magnitudes fainter than the main survey. The spectroscopy is now complete over a contiguous area of 7500 deg^2 in the Northern Galactic Cap, closing the gap that was present in previous data releases. There are over 1.6 million spectra in total, including 930,000 galaxies, 120,000 quasars, and 460,000 stars. The data release includes improved stellar photometry at low Galactic latitude. The astrometry has all been recalibrated with the second version of the USNO CCD Astrograph Catalog (UCAC-2), reducing the rms statistical errors at the bright end to 45 milli-arcseconds per coordinate. A systematic error in bright galaxy photometr is less severe than previously reported for the majority of galaxies. Finally, we describe a series of improvements to the spectroscopic reductions, including better flat-fielding and improved wavelength calibration at the blue end, better processing of objects with extremely strong narrow emission lines, and an improved determination of stellar metallicities. (Abridged)Comment: 20 pages, 10 embedded figures. Accepted to ApJS after minor correction

Dark sectors 2016 Workshop: community report

This report, based on the Dark Sectors workshop at SLAC in April 2016, summarizes the scientific importance of searches for dark sector dark matter and forces at masses beneath the weak-scale, the status of this broad international field, the important milestones motivating future exploration, and promising experimental opportunities to reach these milestones over the next 5-10 years

A Simple Genetic Architecture Underlies Morphological Variation in Dogs

The largest genetic study to date of morphology in domestic dogs identifies genes controlling nearly 100 morphological traits and identifies important trends in phenotypic variation within this species