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Analysis of Morphological Parameters to Differentiate Rupture Status in Anterior Communicating Artery Aneurysms
In contrast to size, the association of morphological characteristics of intracranial aneurysms with rupture has not been established in a systematic manner. We present an analysis of the morphological variables that are associated with rupture in anterior communicating artery aneurysms to determine site-specific risk variables. One hundred and twenty-four anterior communicating artery aneurysms were treated in a single institution from 2005 to 2010, and CT angiograms (CTAs) or rotational angiography from 79 patients (42 ruptured, 37 unruptured) were analyzed. Vascular imaging was evaluated with 3D Slicer© to generate models of the aneurysms and surrounding vasculature. Morphological parameters were examined using univariate and multivariate analysis and included aneurysm volume, aspect ratio, size ratio, distance to bifurcation, aneurysm angle, vessel angle, flow angle, and parent-daughter angle. Multivariate logistic regression revealed that size ratio, flow angle, and parent-daughter angle were associated with aneurysm rupture after adjustment for age, sex, smoking history, and other clinical risk factors. Simple morphological parameters such as size ratio, flow angle, and parent-daughter angle may thus aid in the evaluation of rupture risk of anterior communicating artery aneurysms
Morphological Parameters Associated with Ruptured Posterior Communicating Aneurysms
The rupture risk of unruptured intracranial aneurysms is known to be dependent on the size of the aneurysm. However, the association of morphological characteristics with ruptured aneurysms has not been established in a systematic and location specific manner for the most common aneurysm locations. We evaluated posterior communicating artery (PCoA) aneurysms for morphological parameters associated with aneurysm rupture in that location. CT angiograms were evaluated to generate 3-D models of the aneurysms and surrounding vasculature. Univariate and multivariate analyses were performed to evaluate morphological parameters including aneurysm volume, aspect ratio, size ratio, distance to ICA bifurcation, aneurysm angle, vessel angles, flow angles, and vessel-to-vessel angles. From 2005–2012, 148 PCoA aneurysms were treated in a single institution. Preoperative CTAs from 63 patients (40 ruptured, 23 unruptured) were available and analyzed. Multivariate logistic regression revealed that smaller volume (p = 0.011), larger aneurysm neck diameter (0.048), and shorter ICA bifurcation to aneurysm distance (p = 0.005) were the most strongly associated with aneurysm rupture after adjusting for all other clinical and morphological variables. Multivariate subgroup analysis for patients with visualized PCoA demonstrated that larger neck diameter (p = 0.018) and shorter ICA bifurcation to aneurysm distance (p = 0.011) were significantly associated with rupture. Intracerebral hemorrhage was associated with smaller volume, larger maximum height, and smaller aneurysm angle, in addition to lateral projection, male sex, and lack of hypertension. We found that shorter ICA bifurcation to aneurysm distance is significantly associated with PCoA aneurysm rupture. This is a new physically intuitive parameter that can be measured easily and therefore be readily applied in clinical practice to aid in the evaluation of patients with PCoA aneurysms
Crystallization and X-ray Structure Determination of Cytochrome c_2 from Rhodobacter sphaeroides in Three Crystal Forms
Cytochrome c_2 serves as the secondary electron donor that reduces the photo-oxidized bacteriochlorophyll dimer in photosynthetic bacteria. Cytochrome c_2 from Rhodobacter sphaeroides has been crystallized in three different forms. At high ionic strength, crystals of a hexagonal space group (P6_122) were obtained, while at low ionic strength, triclinic (P1) and tetragonal (P4_12_12) crystals were formed. The three-dimensional structures of the cytochrome in all three crystal forms have been determined by X-ray diffraction at resolutions of 2.20 Ã… (hexagonal), 1.95 Ã…, (triclinic) and 1.53 Ã… (tetragonal). The most significant difference observed was the binding of an imidazole molecule to the iron atom of the heme group in the hexagonal structure. This binding displaces the sulfur atom of Met 100, which forms the axial ligand in the triclinic and tetragonal structures
Report of the Advisory Committee in Seismology
The Advisory Committee in Seismology has pleasure in reporting the
continued progress of its study of California earth movements during
the year 1924-1925 without essential change of plan. A considerable
amount of geologic work in the study of fault zones has been done during
the year in the Mojave Desert and in Death Valley, the system of
primary triangulation for the detection and measurement of horizontal
displacements has progressed rapidly and effectively, and the development
of suitable instruments for determining the two horizontal components
of local earth movements has progressed to completion. Ground
for a new laboratory has been purchased by the California Institute of
Technology and the construction of the central station laboratory building
upon it has been begun. The laboratory is expected to be occupied
by Mr. H. O. Wood, Research Associate in Seismology, and his associates,
about January 1, 1926. It is hoped that additional stations will also
be occupied before the close of the present calendar year (1925), and
that actual work in what has been happily termed the seismologic triangulation
of California will be successfully inaugurated
Endovascular thrombectomy in patients with large core ischemic stroke: a cost-effectiveness analysis from the SELECT study
Background It is unknown whether endovascular thrombectomy (EVT) is cost effective in large ischemic core infarcts.
Methods In the prospective, multicenter, cohort study of imaging selection study (SELECT), large core was defined as computed tomography (CT) ASPECTS(CTP) ischemic core volume (rCBF Results From 361 patients enrolled in SELECT, 105 had large core on CT or CTP (EVT 62, MM 43). 19 (31%) EVT vs 6 (14%) MM patients achieved modified Rankin Scale (mRS) score 0–2 (OR 3.27, 95% CI 1.11 to 9.62, P=0.03) with a shift towards better mRS (cOR 2.12, 95% CI 1.05 to 4.31, P=0.04). Over the projected lifetime of patients presenting with large core, EVT led to incremental costs of 24 665 per QALY. EVT has a higher NMB compared with MM at lower (EVT -76 740) and upper (EVT 57 134) WTP thresholds. PSA confirmed the results and CEAC showed 77% and 92% acceptability of EVT at the WTP of 100 000, respectively. EVT was associated with an increment of 37 901, 22 501 and a gain of 1.62, 2.36 and 2.21 QALYs, respectively. Conclusions In a non-randomized prospective cohort study, EVT resulted in better outcomes in large core patients with higher QALYs, NMB and high cost-effectiveness acceptability rates at current WTP thresholds. Randomized trials are needed to confirm these results. Clinical trial registration NCT0244658
The Relationship Between HR Practices and Firm Performance: Examining Causal Order
Significant research attention has been devoted to examining the relationship between HR practices and firm performance, and the research support has assumed HR as the causal variable. Using data from 45 business units (with 62 data points), this study examines how measures of HR practices correlate with past, concurrent, and future operational performance measures. The results indicate that correlations with performance measures at all three times are both high and invariant, and that controlling for past or concurrent performance virtually eliminates the correlation of HR with future performance. Implications are discussed
Book reviews
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45936/1/357_2005_Article_BF01896816.pd
Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence
Vigorous proliferative CD4+ T cell responses are the hallmark of spontaneous clearance of acute hepatitis C virus (HCV) infection, whereas comparable responses are absent in chronically evolving infection. Here, we comprehensively characterized the breadth, specificity, and quality of the HCV-specific CD4+ T cell response in 31 patients with acute HCV infection and varying clinical outcomes. We analyzed in vitro T cell expansion in the presence of interleukin-2, and ex vivo staining with HCV peptide-loaded MHC class II tetramers. Surprisingly, broadly directed HCV-specific CD4+ T cell responses were universally detectable at early stages of infection, regardless of the clinical outcome. However, persistent viremia was associated with early proliferative defects of the HCV-specific CD4+ T cells, followed by rapid deletion of the HCV-specific response. Only early initiation of antiviral therapy was able to preserve CD4+ T cell responses in acute, chronically evolving infection. Our results challenge the paradigm that HCV persistence is the result of a failure to prime HCV-specific CD4+ T cells. Instead, broadly directed HCV-specific CD4+ T cell responses are usually generated, but rapid exhaustion and deletion of these cells occurs in the majority of patients. The data further suggest a short window of opportunity to prevent the loss of CD4+ T cell responses through antiviral therapy
The Chernobyl childhood leukemia study: background & lessons learned
Many challenges emerged during completion of a study to examine radiation dose and acute leukemia among children in areas of the former Soviet Union. In an era of globalization, our experiences might benefit others involved in multinational investigations
Somatic Variants in SVIL in Cerebral Aneurysms
Publisher Copyright: © American Academy of Neurology.Background and ObjectivesWhile somatic mutations have been well-studied in cancer, their roles in other complex traits are much less understood. Our goal is to identify somatic variants that may contribute to the formation of saccular cerebral aneurysms.MethodsWe performed whole-exome sequencing on aneurysm tissues and paired peripheral blood. RNA sequencing and the CRISPR/Cas9 system were then used to perform functional validation of our results.ResultsSomatic variants involved in supervillin (SVIL) or its regulation were found in 17% of aneurysm tissues. In the presence of a mutation in the SVIL gene, the expression level of SVIL was downregulated in the aneurysm tissue compared with normal control vessels. Downstream signaling pathways that were induced by knockdown of SVIL via the CRISPR/Cas9 system in vascular smooth muscle cells (vSMCs) were determined by evaluating changes in gene expression and protein kinase phosphorylation. We found that SVIL regulated the phenotypic modulation of vSMCs to the synthetic phenotype via Krüppel-like factor 4 and platelet-derived growth factor and affected cell migration of vSMCs via the RhoA/ROCK pathway.DiscussionWe propose that somatic variants form a novel mechanism for the development of cerebral aneurysms. Specifically, somatic variants in SVIL result in the phenotypic modulation of vSMCs, which increases the susceptibility to aneurysm formation. This finding suggests a new avenue for the therapeutic intervention and prevention of cerebral aneurysms.Peer reviewe
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