Mid-term safety and efficacy in small intracranial aneurysm coiling: results from TARGET® nano prospective independent core lab adjudicated multicenter registry.

Background: The primary objective is to evaluate the safety and effectiveness of Stryker second generation Target® Nano Coils in the treatment of ruptured and unruptured small (<7 mm) intracranial aneurysms. Methods: The TARGET Registry is a prospective, two-arm study with independent medical event monitoring and core-lab adjudication. This paper describes the second arm of the TARGET registry. Patients with de novo intracranial aneurysms were embolized with 2nd generation TARGET Nano coils in 12 US centers. The primary efficacy outcome was adequate aneurysm occlusion (RR occlusion grade I-II) on follow-up. Primary safety outcome was treatment-related morbidity and mortality. Secondary outcomes included aneurysm packing density immediately post-procedure, immediate adequate occlusion, aneurysm re-access rate, retreatment rate and clinical outcomes using modified ranking scale. A secondary analysis investigated the influence of using Nano-predominant coils (≥2/3 of total coil-length) vs. non-Nano-predominant coils (<2/3 of total length). Results: 150 patients with 155 aneurysms met the inclusion and exclusion criteria. (31%) patients with ruptured and (69%) with unruptured aneurysms were treated using TARGET coils. Median age was 58.8 (SD 12.7), 74.7% were females, and 80% were Caucasians. Mean follow-up was 5.23 (SD 2.27) months. Peri-procedural mortality was seen in 2.0% of patients. Good outcome at discharge (mRS 0-2) was seen in 81.3% of the cohort. The median packing density (SD) was 29.4% (14.9). Mid-term complete/near complete occlusion rate was seen in 96% of aneurysms and complete obliteration was seen in 75.2% of aneurysms. Patients treated predominantly with Nano coils had higher PD (32.6% vs. 26.1%, p < 0.001). There was no significant difference in clinical and angiographic outcomes. The mid-term mRS0-2 was achieved in 106/109 (97.2%) patients. All-cause mortality was 5/115 (4.3%). Conclusion: In the multicenter TARGET Registry, 75.8% of aneurysms achieved mid-term complete occlusion, and 96% achieved complete/near complete occlusion with excellent independent functional outcome.

High Throughput Tomography (HiTT) on EMBL beamline P14 on PETRA III.

Here, high-throughput tomography (HiTT), a fast and versatile phase-contrast imaging platform for life-science samples on the EMBL beamline P14 at DESY in Hamburg, Germany, is presented. A high-photon-flux undulator beamline is used to perform tomographic phase-contrast acquisition in about two minutes which is linked to an automated data processing pipeline that delivers a 3D reconstructed data set less than a minute and a half after the completion of the X-ray scan. Combining this workflow with a sophisticated robotic sample changer enables the streamlined collection and reconstruction of X-ray imaging data from potentially hundreds of samples during a beam-time shift. HiTT permits optimal data collection for many different samples and makes possible the imaging of large sample cohorts thus allowing population studies to be attempted. The successful application of HiTT on various soft tissue samples in both liquid (hydrated and also dehydrated) and paraffin-embedded preparations is demonstrated. Furthermore, the feasibility of HiTT to be used as a targeting tool for volume electron microscopy, as well as using HiTT to study plant morphology, is demonstrated. It is also shown how the high-throughput nature of the work has allowed large numbers of `identical' samples to be imaged to enable statistically relevant sample volumes to be studied.

Thermoneutral Housing Enables Studies of Vertical Transmission of Obesogenic Diet-Driven Metabolic Diseases.

Vertical transmission of obesity is a critical contributor to the unabated obesity pandemic and the associated surge in metabolic diseases. Existing experimental models insufficiently recapitulate "human-like" obesity phenotypes, limiting the discovery of how severe obesity in pregnancy instructs vertical transmission of obesity. Here, via utility of thermoneutral housing and obesogenic diet feeding coupled to syngeneic mating of WT obese female and lean male mice on a C57BL/6 background, we present a tractable, more "human-like" approach to specifically investigate how maternal obesity contributes to offspring health. Using this model, we found that maternal obesity decreased neonatal survival, increased offspring adiposity, and accelerated offspring predisposition to obesity and metabolic disease. We also show that severe maternal obesity was sufficient to skew offspring microbiome and create a proinflammatory gestational environment that correlated with inflammatory changes in the offspring in utero and adulthood. Analysis of a human birth cohort study of mothers with and without obesity and their infants was consistent with mouse study findings of maternal inflammation and offspring weight gain propensity. Together, our results show that dietary induction of obesity in female mice coupled to thermoneutral housing can be used for future mechanistic interrogations of obesity and metabolic disease in pregnancy and vertical transmission of pathogenic traits.

Extraterrestrial Axion Search with the Breakthrough Listen Galactic Center Survey.

Axion dark matter (DM) may efficiently convert to photons in the magnetospheres of neutron stars (NSs), producing nearly monochromatic radio emission. This process is resonantly triggered when the plasma frequency induced by the underlying charge distribution approximately matches the axion mass. We search for evidence of this process using archival Green Bank Telescope data collected in a survey of the Galactic Center in the C band by the Breakthrough Listen project. While Breakthrough Listen aims to find signatures of extraterrestrial life in the radio band, we show that their high-frequency resolution spectral data of the Galactic Center region is ideal for searching for axion-photon transitions generated by the population of NSs in the inner pc of the Galaxy. We use data-driven models to capture the distributions and properties of NSs in the inner Galaxy and compute the expected radio flux from each NS using state-of-the-art ray tracing simulations. We find no evidence for axion DM and set leading constraints on the axion-photon coupling, excluding values down to the level g_{aγγ}∼10^{-11} GeV^{-1} for DM axions for masses between 15 and 35 µeV.

Stochastic fluctuations of bosonic dark matter.

Numerous theories extending beyond the standard model of particle physics predict the existence of bosons that could constitute dark matter. In the standard halo model of galactic dark matter, the velocity distribution of the bosonic dark matter field defines a characteristic coherence time τc. Until recently, laboratory experiments searching for bosonic dark matter fields have been in the regime where the measurement time T significantly exceeds τc, so null results have been interpreted by assuming a bosonic field amplitude Φ0 fixed by the average local dark matter density. Here we show that experiments operating in the T ≪ τc regime do not sample the full distribution of bosonic dark matter field amplitudes and therefore it is incorrect to assume a fixed value of Φ0 when inferring constraints. Instead, in order to interpret laboratory measurements (even in the event of a discovery), it is necessary to account for the stochastic nature of such a virialized ultralight field. The constraints inferred from several previous null experiments searching for ultralight bosonic dark matter were overestimated by factors ranging from 3 to 10 depending on experimental details, model assumptions, and choice of inference framework.

Immunofluorescence-guided segmentation of three-dimensional features in micro-computed tomography datasets of human lung tissue.

Micro-computed tomography (µCT) provides non-destructive three-dimensional (3D) imaging of soft tissue microstructures. Specific features in µCT images can be identified using correlated two-dimensional (2D) histology images allowing manual segmentation. However, this is very time-consuming and requires specialist knowledge of the tissue and imaging modalities involved. Using a custom-designed µCT system optimized for imaging unstained formalin-fixed paraffin-embedded soft tissues, we imaged human lung tissue at isotropic voxel sizes less than 10 µm. Tissue sections were stained with haematoxylin and eosin or cytokeratin 18 in columnar airway epithelial cells using immunofluorescence (IF), as an exemplar of this workflow. Novel utilization of tissue autofluorescence allowed automatic alignment of 2D microscopy images to the 3D µCT data using scripted co-registration and automated image warping algorithms. Warped IF images, which were accurately aligned with the µCT datasets, allowed 3D segmentation of immunoreactive tissue microstructures in the human lung. Blood vessels were segmented semi-automatically using the co-registered µCT datasets. Correlating 2D IF and 3D µCT data enables accurate identification, localization and segmentation of features in fixed soft lung tissue. Our novel correlative imaging workflow provides faster and more automated 3D segmentation of µCT datasets. This is applicable to the huge range of formalin-fixed paraffin-embedded tissues held in biobanks and archives.

Study of the Pathogen Inactivation Mechanism in Salt-Coated Filters.

As COVID-19 exemplifies, respiratory diseases transmitted through aerosols or droplets are global threats to public health, and respiratory protection measures are essential first lines of infection prevention and control. However, common face masks are single use and can cause cross-infection due to the accumulated infectious pathogens. We developed salt-based formulations to coat membrane fibers to fabricate antimicrobial filters. Here, we report a mechanistic study on salt-induced pathogen inactivation. The salt recrystallization following aerosol exposure was characterized over time on sodium chloride (NaCl), potassium sulfate (K2SO4), and potassium chloride (KCl) powders and coatings, which revealed that NaCl and KCl start to recrystallize within 5 min and K2SO4 within 15 min. The inactivation kinetics observed for the H1N1 influenza virus and Klebsiella pneumoniae matched the salt recrystallization well, which was identified as the main destabilizing mechanism. Additionally, the salt-coated filters were prepared with different methods (with and without a vacuum process), which led to salt coatings with different morphologies for diverse applications. Finally, the salt-coated filters caused a loss of pathogen viability independent of transmission mode (aerosols or droplets), against both DI water and artificial saliva suspensions. Overall, these findings increase our understanding of the salt-recrystallization-based technology to develop highly versatile antimicrobial filters.

Search for Axionlike Dark Matter Using Solid-State Nuclear Magnetic Resonance.

We report the results of an experimental search for ultralight axionlike dark matter in the mass range 162-166 neV. The detection scheme of our Cosmic Axion Spin Precession Experiment is based on a precision measurement of ^{207}Pb solid-state nuclear magnetic resonance in a polarized ferroelectric crystal. Axionlike dark matter can exert an oscillating torque on ^{207}Pb nuclear spins via the electric dipole moment coupling g_{d} or via the gradient coupling g_{aNN}. We calibrate the detector and characterize the excitation spectrum and relaxation parameters of the nuclear spin ensemble with pulsed magnetic resonance measurements in a 4.4 T magnetic field. We sweep the magnetic field near this value and search for axionlike dark matter with Compton frequency within a 1 MHz band centered at 39.65 MHz. Our measurements place the upper bounds |g_{d}|<9.5×10^{-4} GeV^{-2} and |g_{aNN}|<2.8×10^{-1} GeV^{-1} (95% confidence level) in this frequency range. The constraint on g_{d} corresponds to an upper bound of 1.0×10^{-21} e cm on the amplitude of oscillations of the neutron electric dipole moment and 4.3×10^{-6} on the amplitude of oscillations of CP-violating θ parameter of quantum chromodynamics. Our results demonstrate the feasibility of using solid-state nuclear magnetic resonance to search for axionlike dark matter in the neV mass range.

Maternal regulation of inflammatory cues is required for induction of preterm birth.

Infection-driven inflammation in pregnancy is a major cause of spontaneous preterm birth (PTB). Both systemic infection and bacterial ascension through the vagina/cervix to the amniotic cavity are strongly associated with PTB. However, the contribution of maternal or fetal inflammatory responses in the context of systemic or localized models of infection-driven PTB is not well defined. Here, using intraperitoneal or intraamniotic LPS challenge, we examined the necessity and sufficiency of maternal and fetal Toll-like receptor (TLR) 4 signaling in induction of inflammatory vigor and PTB. Both systemic and local LPS challenge promoted induction of inflammatory pathways in uteroplacental tissues and induced PTB. Restriction of TLR4 expression to the maternal compartment was sufficient for induction of LPS-driven PTB in either systemic or intraamniotic challenge models. In contrast, restriction of TLR4 expression to the fetal compartment failed to induce LPS-driven PTB. Vav1-Cre-mediated genetic deletion of TLR4 suggested a critical role for maternal immune cells in inflammation-driven PTB. Further, passive transfer of WT in vitro-derived macrophages and dendritic cells to TLR4-null gravid females was sufficient to induce an inflammatory response and drive PTB. Cumulatively, these findings highlight the critical role for maternal regulation of inflammatory cues in induction of inflammation-driven parturition.

Tunable Axion Plasma Haloscopes.

We propose a new strategy for searching for dark matter axions using tunable cryogenic plasmas. Unlike current experiments, which repair the mismatch between axion and photon masses by breaking translational invariance (cavity and dielectric haloscopes), a plasma haloscope enables resonant conversion by matching the axion mass to a plasma frequency. A key advantage is that the plasma frequency is unrelated to the physical size of the device, allowing large conversion volumes. We identify wire metamaterials as a promising candidate plasma, wherein the plasma frequency can be tuned by varying the interwire spacing. For realistic experimental sizes, we estimate competitive sensitivity for axion masses of 35-400 µeV, at least.

Penetrating intracranial trauma of two minors treated with endovascular technique with the use of temporary balloon occlusion for proximal arterial control.

We present two children treated with endovascular techniques to gain proximal arterial control of the internal carotid and vertebral artery prior to removal of penetrating objects from the skull base. Both siblings (8-month-old and 22-month-old boys) were injured by different sharp objects (knife and scissor) by a guardian. They were transported to the emergency room where vascular control, including coil embolisation and internal carotid balloon occlusion, was performed in the neuroendovascular suite for safe removal of penetrating objects. Both minors recovered and were discharged home without any focal neurological deficits. In two children with scissor and knife stab with intracranial penetration, endovascular technique allowed safe removal of objects and ensured proximal arterial control was maintained to control for possible extravasation of blood on removal from the skull base.

Central ANG-(1-7) infusion improves blood pressure regulation in antenatal betamethasone-exposed sheep and reveals sex-dependent effects on oxidative stress.

Fetal exposure to betamethasone (BMX) as a consequence of glucocorticoid administration to women threatening premature delivery may lead to long-term deleterious effects on the cardiovascular system and dysregulation of blood pressure in exposed adults. Indeed, adult offspring of BMX sheep exhibit increased mean arterial pressure (MAP) and attenuated baroreflex sensitivity (BRS) that are associated with lower medullary and cerebrospinal fluid (CSF) angiotensin-(1-7) [(ANG-(1-7)] content. Thus we determined the effects of ANG-(1-7) supplementation in the CSF on MAP, BRS, blood pressure (BPV) and heart rate variability (HRV) in conscious animals. The peptide or artificial CSF (aCSF) was infused continuously into the lateral ventricle (intracerebroventricular) of 4-mo-old male and female BMX sheep for 2 wk. Analysis of data from males and females combined revealed that intracerebroventricular ANG-(1-7) significantly lowered MAP and heart rate and improved BRS as compared with baseline; intracerebroventricular aCSF did not change these indexes. Similar patterns were observed for altered hemodynamics and autonomic function produced by intracerebroventricular ANG-(1-7) in both sexes. Oxidative stress and MAP kinase (MAPK) activation were lower in tissues from the dorsomedial medulla (DMM) of ANG-(1-7)-treated males but were unchanged in the treated females, when assessed at the end of the treatment period. We conclude that in the face of ANG-(1-7) deficiency in CSF and medullary tissue in BMX sheep intracerebroventricular supplementation of ANG-(1-7) lowers MAP and restores the impaired autonomic function to a similar degree in both males and females; however, the attenuation of MAPK and oxidative stress within the DMM was evident only in males. NEW & NOTEWORTHY We demonstrate that intracerebroventricular angiotensin-(1-7) [(ANG-(1-7)] treatment for 2 wk in antenatal betamethasone-exposed sheep provides beneficial effects on blood pressure and autonomic function. The physiological improvements are accompanied by an attenuation of oxidative stress in males but not females. The finding that ANG-(1-7) supplementation lowers blood pressure and restores the impaired autonomic function in a model of fetal programming previously shown to exhibit a deficiency in cerebrospinal fluid and brain tissue illustrates the potential for new therapeutic strategies for reducing cardiovascular dysfunction arising from prenatal events.

Defect generation in TiO2 nanotube anodes via heat treatment in various atmospheres for lithium-ion batteries.

In this paper, ordered TiO2 nanotubes were grown on a Ti substrate via electrochemical anodization and subsequently annealed at 450 °C for 4 h under various atmospheres to create different point defects. Oxygen-deficient environments such as Ar and N2 were used to develop oxygen vacancies, while a water vapor (WV) atmosphere was used to generate titanium vacancies. Computational models by density functional theory predicted that the presence of oxygen vacancies would cause electronic conductivity to increase, while the presence of Ti vacancies could lead to decreased conductivity. The predictions were confirmed by two-point electrical conductivity measurements and Mott-Schottky analysis. Raman spectroscopy was also conducted to confirm the presence of defects. The annealed samples were then evaluated as anodes in lithium-ion batteries. The oxygen-deficient samples had an improvement in capacity by 10% and 25% for Ar- and N2-treated samples, respectively, while the WV-treated sample displayed a capacity increase of 24% compared to the stoichiometric control sample (annealed in O2). Electrochemical impedance spectroscopy studies revealed that the WV-treated sample's increased capacity was a consequence of its higher Li diffusivity. The results suggest that balanced electrical and ionic conductivity in nanostructured metal oxide anodes can be tuned through defect generation using heat treatments in various atmospheres for improved electrochemical properties.

Differential outcomes of TLR2 engagement in inflammation-induced preterm birth.

Preterm birth (PTB) is the leading cause of neonatal mortality worldwide. Infection and inflammation are considered main causes of PTB. Among multiple pathogens, Gram-positive bacteria are commonly linked with induction of PTB. Although activation of innate immune responses, via TLR2 engagement, by Gram-positive bacteria is a likely cause, whether induction of PTB depends on the potency of specific microbial components to induce Toll-like receptor (TLR)2-driven inflammation has not been elucidated. Here, we show that TLR2 activation by synthetic lipopeptides, Pam2Cys, and Pam3Cys specifically, variably influenced inflammation and subsequent induction of PTB. Pam2Cys challenge, compared to Pam3Cys, induced PTB and promoted significantly higher expression of inflammatory cytokines, specifically IL-6 and IFN-ß, both in vivo and in vitro. Notably, antibody-mediated neutralization of IL-6 or genetic deletion of type I IFN receptor (IFNAR) was sufficient to protect from Pam2Cys-driven PTB and to temper excessive proinflammatory cytokine production. Conversely, IFN-ß or IL-6 was not sufficient to promote induction of PTB by Pam3Cys. In summary, our data implies a divergent function of TLR2-activating lipopeptides in the magnitude and type of ligand-driven inflammatory vigor in induction of PTB.

Erratum: Thermoneutral housing exacerbates nonalcoholic fatty liver disease in mice and allows for sex-independent disease modeling.

This corrects the article DOI: 10.1038/nm.4346.

Thermoneutral housing exacerbates nonalcoholic fatty liver disease in mice and allows for sex-independent disease modeling.

Nonalcoholic fatty liver disease (NAFLD), a common prelude to cirrhosis and hepatocellular carcinoma, is the most common chronic liver disease worldwide. Defining the molecular mechanisms underlying the pathogenesis of NAFLD has been hampered by a lack of animal models that closely recapitulate the severe end of the disease spectrum in humans, including bridging hepatic fibrosis. Here we demonstrate that a novel experimental model employing thermoneutral housing, as opposed to standard housing, resulted in lower stress-driven production of corticosterone, augmented mouse proinflammatory immune responses and markedly exacerbated high-fat diet (HFD)-induced NAFLD pathogenesis. Disease exacerbation at thermoneutrality was conserved across multiple mouse strains and was associated with augmented intestinal permeability, an altered microbiome and activation of inflammatory pathways that are associated with the disease in humans. Depletion of Gram-negative microbiota, hematopoietic cell deletion of Toll-like receptor 4 (TLR4) and inactivation of the IL-17 axis resulted in altered immune responsiveness and protection from thermoneutral-housing-driven NAFLD amplification. Finally, female mice, typically resistant to HFD-induced obesity and NAFLD, develop full disease characteristics at thermoneutrality. Thus, thermoneutral housing provides a sex-independent model of exacerbated NAFLD in mice and represents a novel approach for interrogation of the cellular and molecular mechanisms underlying disease pathogenesis.

Type I interferons regulate susceptibility to inflammation-induced preterm birth.

Preterm birth (PTB) is a leading worldwide cause of morbidity and mortality in infants. Maternal inflammation induced by microbial infection is a critical predisposing factor for PTB. However, biological processes associated with competency of pathogens, including viruses, to induce PTB or sensitize for secondary bacterial infection-driven PTB are unknown. We show that pathogen/pathogen-associated molecular pattern-driven activation of type I IFN/IFN receptor (IFNAR) was sufficient to prime for systemic and uterine proinflammatory chemokine and cytokine production and induction of PTB. Similarly, treatment with recombinant type I IFNs recapitulated such effects by exacerbating proinflammatory cytokine production and reducing the dose of secondary inflammatory challenge required for induction of PTB. Inflammatory challenge-driven induction of PTB was eliminated by defects in type I IFN, TLR, or IL-6 responsiveness, whereas the sequence of type I IFN sensing by IFNAR on hematopoietic cells was essential for regulation of proinflammatory cytokine production. Importantly, we also show that type I IFN priming effects are conserved from mice to nonhuman primates and humans, and expression of both type I IFNs and proinflammatory cytokines is upregulated in human PTB. Thus, activation of the type I IFN/IFNAR axis in pregnancy primes for inflammation-driven PTB and provides an actionable biomarker and therapeutic target for mitigating PTB risk.

Flow failure from intracranial atherosclerotic disease: a rationale for endovascular intervention in a population with recurrent symptoms despite maximal medical therapy.

The Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) trial, the first randomized trial to compare best medical therapies with angioplasty and stenting, was halted prematurely owing to a 30-day stroke rate of 14.7% in the angioplasty and stenting arm compared with 5.8% in the medical management arm. These results have led to a paradigm shift away from interventional therapies and back to dual antiplatelet therapy and aggressive medical therapies only for these patients. However, there appears to be a subset of patients with intracranial atherosclerotic disease (ICAD) who are different from the general SAMMPRIS cohort and are defined by flow failure from severe intracranial arterial stenosis resulting in recurrent ischemic symptoms despite maximal medical therapy. Offering the option of endovascular revascularization seems appropriate in this patient population, given their recurrent ischemic events regardless of aggressive medical therapies. This paper provides a rationale for reconsidering the role of interventional therapies in patients with critical intracranial stenosis and presents four patients with flow failure from ICAD and persistent symptoms of ischemia, regardless of dual antiplatelet and adjuvant medical therapies, who subsequently improved with angioplasty. Consideration of alternative patient populations and treatment paradigms seems to carry particular relevance now as the endovascular treatment of intracranial atheromatous disease is currently receiving intense scrutiny by those medical specialties involved in the care of stroke patients, as well as the public at large.

The stent anchor technique for distal access through a large or giant aneurysm.

Large and giant aneurysms pose significant challenges to the endovascular techniques of coil embolization or parent vessel reconstruction. Many large aneurysms are wide-necked with bulbous domes and frequently require stent-assisted coiling or flow diversion to reconstruct and preserve flow through the parent artery. Often the wire must be looped in the dome before catheterization of the exiting portion of the parent vessel is possible. In addition, it can be challenging to obtain stable distal purchase of the microcatheter that will allow the loop to be withdrawn from the aneurysm without the entire microcatheter unwinding, resulting in herniation into the aneurysm or proximal vessels. The stent anchor technique, a novel method of obtaining distal purchase that allows straightening of the catheter loop within a large aneurysm for the purposes of stenting for vessel reconstruction across large or giant aneurysms, is presented. This technique may facilitate the use of new stent technologies in the treatment of large aneurysms that have traditionally been exceedingly difficult to treat via an endovascular approach.

Rationale for treating unruptured intracranial aneurysms: actuarial analysis of natural history risk versus treatment risk for coiling or clipping based on 14,050 patients in the Nationwide Inpatient Sample database.

OBJECTIVE: The treatment of small unruptured intracranial aneurysms has been questioned based on the results of the International Study of Unruptured Intracranial Aneurysms. Our objective was to compare natural history rupture risk versus treatment risk for coiling and clipping small unruptured aneurysms using data in the Nationwide Inpatient Sample database. METHODS: Data for clipping and coiling of unruptured aneurysms was collected from the Nationwide Inpatient Sample from 2002-2008. Treatment risks were adjusted for age, gender, and medical comorbidities. Logistic regression models were used to create curves depicting the estimated probability of poor outcome as a function of patient age for clipping and coiling. These treatment risk curves were compared against natural history actuarial risk curves calculated from four prominent studies. RESULTS: There were 14,050 hospitalizations: 7439(53%) coiling; 6611(47%) clipping. For patients who underwent coiling or clipping, the mortality rate was 2.17% and 2.66%, and the morbidity rate was 2.16% and 4.75%, respectively. The adjusted risk of poor outcome from clipping and coiling, when modeled against most natural history studies, demonstrates a treatment benefit for clipping for patients <70 years and for coiling patients <81 years. Models using the International Study of Unruptured Intracranial Aneurysms data demonstrate a treatment benefit for clipping for patients <61 years and for coiling for patients <70 years. CONCLUSIONS: Both clipping and coiling of unruptured intracranial aneurysms are safe. This analysis demonstrates rationale for clipping small unruptured aneurysms in patients <61-70 years and coiling small unruptured aneurysms in patients <70-80 years. Treatment beyond these age ranges is associated with increased risk of poor outcome.