High-resolution 3D X-ray imaging of intracranial nitinol stents

Introduction To assess an optimized 3D imaging protocol for intracranial nitinol stents in 3D C-arm flat detector imaging. For this purpose, an image quality simulation and an in vitro study was carried out. Methods Nitinol stents of various brands were placed inside an anthropomorphic head phantom, using iodine contrast. Experiments with objects were preceded by image quality and dose simulations. We varied X-ray imaging parameters in a commercially interventional X-ray system to set 3D image quality in the contrast–noise–sharpness space. Beam quality was varied to evaluate contrast of the stents while keeping absorbed dose below recommended values. Two detector formats were used, paired with an appropriate pixel size and X-ray focus size. Zoomed reconstructions were carried out and snapshot images acquired. High contrast spatial resolution was assessed with a CT phantom. Results We found an optimal protocol for imaging intracranial nitinol stents. Contrast resolution was optimized for nickel–titanium-containing stents. A high spatial resolution larger than 2.1 lp/mm allows struts to be visualized. We obtained images of stents of various brands and a representative set of images is shown. Independent of the make, struts can be imaged with virtually continuous strokes. Measured absorbed doses are shown to be lower than 50 mGy Computed Tomography Dose Index (CTDI). Conclusion By balancing the modulation transfer of the imaging components and tuning the high-contrast imaging capabilities, we have shown that thin nitinol stent wires can be reconstructed with high contrast-to-noise ratio and good detail, while keeping radiation doses within recommended values. Experimental results compare well with imaging simulations

The unexplained success of stentplasty vasospasm treatment

Background Cerebral vasospasm (CVS) following subarachnoid hemorrhage occurs in up to 70% of patients. Recently, stents have been used to successfully treat CVS. This implies that the force required to expand spastic vessels and resolve vasospasm is lower than previously thought. Objective We develop a mechanistic model of the spastic arterial wall to provide insight into CVS and predict the forces required to treat it. Material and Methods The arterial wall is modelled as a cylindrical membrane using a constrained mixture theory that accounts for the mechanical roles of elastin, collagen and vascular smooth muscle cells (VSMC). We model the pressure diameter curve prior to CVS and predict how it changes following CVS. We propose a stretch-based damage criterion for VSMC and evaluate if several commercially available stents are able to resolve vasospasm. Results The model predicts that dilatation of VSMCs beyond a threshold of mechanical failure is sufficient to resolve CVS without damage to the underlying extracellular matrix. Consistent with recent clinical observations, our model predicts that existing stents have the potential to provide sufficient outward force to successfully treat CVS and that success will be dependent on an appropriate match between stent and vessel. Conclusion Mathematical models of CVS can provide insights into biological mechanisms and explore treatment approaches. Improved understanding of the underlying mechanistic processes governing CVS and its mechanical treatment may assist in the development of dedicated stents

Direct targets of the transcription factors ABA-Insensitive(ABI)4 and ABI5 reveal synergistic action by ABI4 and several bZIP ABA response factors

The plant hormone abscisic acid (ABA) is a key regulator of seed development. In addition to promoting seed maturation, ABA inhibits seed germination and seedling growth. Many components involved in ABA response have been identified, including the transcription factors ABA insensitive (ABI)4 and ABI5. The genes encoding these factors are expressed predominantly in developing and mature seeds, and are positive regulators of ABA mediated inhibition of seed germination and growth. The direct effects of ABI4 and ABI5 in ABA response remain largely undefined. To address this question, plants over-expressing ABI4 or ABI5 were used to allow identification of direct transcriptional targets. Ectopically expressed ABI4 and ABI5 conferred ABA-dependent induction of slightly over 100 genes in 11 day old plants. In addition to effector genes involved in seed maturation and reserve storage, several signaling proteins and transcription factors were identified as targets of ABI4 and/or ABI5. Although only 12% of the ABA- and ABI-dependent transcriptional targets were induced by both ABI factors in 11 day old plants, 40% of those normally expressed in seeds had reduced transcript levels in both abi4 and abi5 mutants. Surprisingly, many of the ABI4 transcriptional targets do not contain the previously characterized ABI4 binding motifs, the CE1 or S box, in their promoters, but some of these interact with ABI4 in electrophoretic mobility shift assays, suggesting that sequence recognition by ABI4 may be more flexible than known canonical sequences. Yeast one-hybrid assays demonstrated synergistic action of ABI4 with ABI5 or related bZIP factors in regulating these promoters, and mutant analyses showed that ABI4 and these bZIPs share some functions in plants

Joint registry approach for identification of outlier prostheses

Background and purposeJoint Replacement Registries play a significant role in monitoring arthroplasty outcomes by publishing data on survivorship of individual prostheses or combinations of prostheses. The difference in outcomes can be device- or non-device-related, and these factors can be analyzed separately. Although registry data indicate that most prostheses have similar outcomes, some have a higher than anticipated rate of revision when compared to all other prostheses in their class. This report outlines how the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) has developed a method to report prostheses with a higher than expected rate of revision. These are referred to as "outlier" prostheses.Material and methodsSince 2004, the AOANJRR has developed a standardized process for identifying outliers. This is based on a 3-stage process consisting of an automated algorithm, an extensive analysis of individual prostheses or combinations by registry staff, and finally a meeting involving a panel from the Australian Orthopaedic Association Arthroplasty Society. Outlier prostheses are listed in the Annual Report as (1) identified but no longer used in Australia, (2) those that have been re-identified and that are still used, and (3) those that are being identified for the first time.Results78 prostheses or prosthesis combinations have been identified as being outliers using this approach (AOANJRR 2011 Annual Report). In addition, 5 conventional hip prostheses were initially identified, but after further analysis no longer met the defined criteria. 1 resurfacing hip prosthesis was initially identified, subsequently removed from the list, and then re-identified the following year when further data were available. All unicompartmental and primary total knee prostheses identified as having a higher than expected rate of revision have continued to be re-identified.InterpretationIt is important that registries use a transparent and accountable process to identify an outlier prosthesis. This paper describes the development, implementation, assessment, and impact of the approach used by the Australian Registry.Richard N de Steiger, Lisa N Miller, David C Davidson, Philip Ryan and Stephen E Grave

Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (OR=1.11, P=5.7×10−15), which persisted after excluding loci implicated in previous studies (OR=1.07, P=1.7 ×10−6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 ×10−11) and neurobehavioral phenotypes in mouse (OR = 1.18, P= 7.3 ×10−5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by non-allelic homologous recombination

No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe