Decision-making in aortic root surgery in Marfan syndrome: bleeding, thromboembolism and risk of reintervention after valve-sparing or mechanical aortic root replacement†

OBJECTIVES Valve-sparing root replacement (VSRR) is thought to reduce the rate of thromboembolic and bleeding events compared with aortic root replacement using a mechanical aortic root replacement (MRR) with a composite graft by avoiding oral anticoagulation. But as VSRR carries a certain risk for subsequent reinterventions, decision-making in the individual patient can be challenging. METHODS Of 100 Marfan syndrome (MFS) patients who underwent 169 aortic surgeries and were followed at our institution since 1995, 59 consecutive patients without a history of dissection or prior aortic surgery underwent elective VSRR or MRR and were retrospectively analysed. RESULTS VSRR was performed in 29 (David n = 24, Yacoub n = 5) and MRR in 30 patients. The mean age was 33 ± 15 years. The mean follow-up after VSRR was 6.5 ± 4 years (180 patient-years) compared with 8.8 ± 9 years (274 patient-years) after MRR. Reoperation rates after root remodelling (Yacoub) were significantly higher than after the reimplantation (David) procedure (60 vs 4.2%, P = 0.01). The need for reinterventions after the reimplantation procedure (0.8% per patient-year) was not significantly higher than after MRR (P = 0.44) but follow-up after VSRR was significantly shorter (P = 0.03). There was neither significant morbidity nor mortality associated with root reoperations. There were no neurological events after VSRR compared with four stroke/intracranial bleeding events in the MRR group (log-rank, P = 0.11), translating into an event rate of 1.46% per patient-year following MRR. CONCLUSION The calculated annual failure rate after VSRR using the reimplantation technique was lower than the annual risk for thromboembolic or bleeding events. Since the perioperative risk of reinterventions following VSRR is low, patients might benefit from VSRR even if redo surgery may become necessary during follow-u

The Internet information infrastructure: Terrorist tool or architecture for information defense?

The Internet is a culmination of information age technologies and an agent of change. As with any infrastructure, dependency upon the so-called global information infrastructure creates vulnerabilities. Moreover, unlike physical infrastructures, the Internet is a multi-use technology. While information technologies, such as the Internet, can be utilized as a tool of terror, these same technologies can facilitate the implementation of solutions to mitigate the threat. In this vein, this paper analyzes the multifaceted nature of the Internet information infrastructure and argues that policymakers should concentrate on the solutions it provides rather than the vulnerabilities it creates. Minimizing risks and realizing possibilities in the information age will require institutional activities that translate, exploit and convert information technologies into positive solutions. What follows is a discussion of the Internet information infrastructure as it relates to increasing vulnerabilities and positive potential. The following four applications of the Internet will be addressed: as the infrastructure for information competence; as a terrorist tool; as the terrorist`s target; and as an architecture for rapid response

Outcome of aortic surgery in patients with Loeys-Dietz syndrome primarily treated as having Marfan syndrome†

OBJECTIVES Loeys-Dietz syndrome (LDS) is characterized by acute aortic dissection (AAD) at aortic diameters below thresholds for intervention in patients with Marfan syndrome (MFS). The aim was to evaluate the outcome of LDS patients primarily treated as having MFS. METHODS We analysed 68 consecutive patients who underwent surgery between 1995 and 2007 under the assumption of having MFS before retrospectively being screened for LDS when genetic testing became available. These patients were followed up until 2013, and underwent a total of 115 aortic surgeries. RESULTS Genetic testing was performed in 76% of the patients. Sixty per cent of these patients were positive for FBN1 mutations associated with MFS, 20% had no FBN1 mutation and 17% harboured TGFBR1/2 mutations associated with LDS. Mean follow-up was 12.7 ± 7 years. All-cause 30-day, 6-month and 1-year mortality rates were 2.9, 4.4 and 7.3%, respectively. Interestingly, initial presentation with AAD did not differ between LDS and MFS (33 vs 37%, P = 0.48) nor did long-term mortality compared with MFS patients (11 vs 16%, P = 1.0) or within MFS subgroups (FBN1 positive 13%, P = 1.0; FBN1 negative 10%, P = 1.0; not tested 25%, P = 0.62). There was no difference in the need for secondary total arch replacement between LDS and MFS patients (11 vs 14%, P = 1.0), nor within MFS subgroups (FBN1 positive 16%, P = 1.0; FBN1 negative 10%, P = 1.0; not tested 13%, P = 1.0). Total aortic replacement became necessary in 22% of LDS compared with 12% of MFS patients (P = 0.6) and did not differ significantly between MFS subgroups. CONCLUSIONS Although early surgical intervention in LDS is warranted to avoid AAD, the current data suggest that once the diseased segment is repaired, there seems to be no additional burden in terms of mortality or reoperation rate compared with that in MFS patients, with or without confirmed FBN1 mutatio

Should aortic arch replacement be performed during initial surgery for aortic root aneurysm in patients with Marfan syndrome?†

OBJECTIVES The aim of this study was to investigate whether total arch replacement (TAR) during initial surgery for root aneurysm should be routinely performed in patients with Marfan syndrome (MFS). METHODS Retrospective analysis of 94 consecutive MFS patients fulfilling Ghent criteria who underwent 148 aortic surgeries and were followed at this institution during the past 16 years. RESULTS The mean follow-up interval was 8.8 ± 7 years. Initial presentation was acute aortic dissection (AAD) in 35% of patients (76% Type A and 24% Type B) and aneurismal disease in 65%. TAR was performed in 8% of patients during initial surgery for AAD (otherwise a hemi-arch replacement was performed) and 1.6% in elective root repair. Secondary TAR had to be performed in only 3% of patients without, but in 33% following AAD (33% Type A and 33% Type B; P = 0.0001). Thirty-day, 6-month, 1-year and overall mortalities were 3.2, 5.3, 6.4 and 11.7%, respectively. Operative and 30-day mortalities in secondary aortic arch replacement were zero. Secondary TAR after AAD did not increase the need for the replacement of the entire thoracoabdominal aorta during follow-up compared with patients without secondary TAR (37 vs 40%, P = 1.0). CONCLUSIONS MFS patients undergoing elective root repair have small risk of reinterventions on the aortic arch, and primary prophylactic replacement does not seem to be justified. In patients with AAD, the need for reinterventions is precipitated by the dissection itself and not by limiting the procedure to the hemi-arch replacement in the emergency setting. Limiting surgery to the aortic root, ascending aorta and proximal aortic arch is associated with low mortality in MFS patients presenting with AA

Single Low-Dose Targeted Bevacizumab Infusion in Adult Patients with Steroid-Refractory Radiation Necrosis of the Brain: A Phase II Open-Label Prospective Clinical Trial

OBJECTIVE There is an unmet need for safe and rapidly effective therapies for refractory brain radiation necrosis (RN). The aim of this prospective single-arm phase II trial was to evaluate the safety and efficacy of a single low-dose targeted bevacizumab infusion after blood-brain barrier disruption (BBBD) in adult patients with steroid-refractory brain RN. METHODS Ten adults with steroid-refractory, imaging-confirmed brain RN were enrolled between November 2016 and January 2018 and followed for 12 months after treatment. Bevacizumab 2.5 mg/kg was administered as a one-time targeted intra-arterial infusion immediately after BBBD. Primary outcomes included safety and \u3e 25% decrease in lesion volume. Images were analyzed by a board-certified neuroradiologist blinded to pretrial diagnosis and treatment status. Secondary outcomes included changes in headache, steroid use, and functional status and absence of neurocognitive sequelae. Comparisons were analyzed using the Fisher exact test, Mann-Whitney U-test, linear mixed models, Wilcoxon signed-rank test, and repeated-measures 1-way ANOVA. RESULTS Ten adults (mean ± SD [range] age 35 ± 15 [22-62] years) participated in this study. No patients died or exhibited serious adverse effects of systemic bevacizumab. At 3 months, 80% (95% CI 44%-98%) and 90% (95% CI 56%-100%) of patients demonstrated \u3e 25% decrease in RN and vasogenic edema volume, respectively. At 12 months, RN volume decreased by 74% (median [range] 76% [53%-96%], p = 0.012), edema volume decreased by 50% (median [range] 70% [-11% to 83%], p = 0.086), and headache decreased by 84% (median [range] 92% [58%-100%], p = 0.022) among the 8 patients without RN recurrence. Only 1 (10%) patient was steroid dependent at the end of the trial. Scores on 12 of 16 (75%) neurocognitive indices increased, thereby supporting a pattern of cerebral white matter recovery. Two (20%) patients exhibited RN recurrence that required further treatment at 10 and 11 months, respectively, after bevacizumab infusion. CONCLUSIONS For the first time, to the authors\u27 knowledge, the authors demonstrated that a single low-dose targeted bevacizumab infusion resulted in durable clinical and imaging improvements in 80% of patients at 12 months after treatment without adverse events attributed to bevacizumab alone. These findings highlight that targeted bevacizumab may be an efficient one-time treatment for adults with brain RN. Further confirmation with a randomized controlled trial is needed to compare the intra-arterial approach with the conventional multicycle intravenous regimen

CIRSE Vascular Closure Device Registry

The conclusion of this registry of closure devices with an anchor and a plug is that the use of this device in interventional radiology procedures is safe, with a low incidence of serious access site complications. There seems to be no difference in complications between antegrade and retrograde access and other parameters

Mechanisms of Thermal Adaptation Revealed From the Genomes of the Antarctic Archaea Methanogenium frigidum and Methanococcoides burtonii

We generated draft genome sequences for two cold-adapted Archaea, Methanogenium frigidum and Methanococcoides burtonii, to identify genotypic characteristics that distinguish them from Archaea with a higher optimal growth temperature (OGT). Comparative genomics revealed trends in amino acid and tRNA composition, and structural features of proteins. Proteins from the cold-adapted Archaea are characterized by a higher content of noncharged polar amino acids, particularly Gin and Thr and a lower content of hydrophobic amino acids, particularly Leu. Sequence data from nine methanogen genomes (OGT 15degrees-98degreesC) were used to generate IIII modeled protein structures. Analysis of the models from the cold-adapted Archaea showed a strong tendency in the solvent-accessible area for more Gin, Thr, and hydrophobic residues and fewer charged residues. A cold shock domain (CSD) protein (CspA homolog) was identified in M. frigidum, two hypothetical proteins with CSD-folds in M. burtonii, and a unique winged helix DNA-binding domain protein in M. burtonii. This suggests that these types of nucleic acid binding proteins have a critical role in cold-adapted Archaea. Structural analysis of tRNA sequences from the Archaea indicated that GC content is the major factor influencing tRNA stability in hyperthermophiles, but not in the psychrophiles, mesophiles or moderate thermophiles. Below an OGT of 60degreesC, the GC content in tRNA was largely unchanged, indicating that any requirement for flexibility of tRNA in psychrophiles is mediated by other means. This is the first time that comparisons have been performed with genome data from Archaea spanning the growth temperature extremes. from psychrophiles to hyperthermophile

Summary for policymakers

The Working Group III contribution to the IPCC Fifth Assessment Report (WGIII AR5) provides a comprehensive assessment of all relevant options for mitigating climate change through limiting or preventing greenhouse gas emissions, as well as activities that remove them from the atmosphere. It draws on scientific literature accepted for publication prior to 4 October 2013. The WGIII Summary for Policymakers was approved at the Twelfth Session of Working Group III, held in Berlin, Germany, from 7 to 11 April, 2014. During the session, the IPCC plenary also accepted the underlying scientific and technical assessment, which stands at 2000 pages, including more than 700 pages of references

Technical summary

The Working Group III (WGIII) contribution to the IPCC's Fifth Assessment Report (AR5) assesses literature on the scientific, technological, environmental, economic and social aspects of mitigation of climate change. It builds upon the WGIII contribution to the IPCC's Fourth Assessment Report (AR4), the Special Report on Renewable Energy Sources and Climate Change Mitigation (SRREN) and previous reports and incorporates subsequent new findings and research. Throughout, the focus is on the implications of its findings for policy, without being prescriptive about the particular policies that governments and other important participants in the policy process should adopt. In light of the IPCC's mandate, authors in WGIII were guided by several principles when assembling this assessment: (1) to be explicit about mitigation options, (2) to be explicit about their costs and about their risks and opportunities vis-a-vis other development priorities, (3) and to be explicit about the underlying criteria, concepts, and methods for evaluating alternative policies. This summary offers the main findings of the report

Cerebellar Nuclear Neurons Use Time and Rate Coding to Transmit Purkinje Neuron Pauses

Copyright: © 2015 Sudhakar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedNeurons of the cerebellar nuclei convey the final output of the cerebellum to their targets in various parts of the brain. Within the cerebellum their direct upstream connections originate from inhibitory Purkinje neurons. Purkinje neurons have a complex firing pattern of regular spikes interrupted by intermittent pauses of variable length. How can the cerebellar nucleus process this complex input pattern? In this modeling study, we investigate different forms of Purkinje neuron simple spike pause synchrony and its influence on candidate coding strategies in the cerebellar nuclei. That is, we investigate how different alignments of synchronous pauses in synthetic Purkinje neuron spike trains affect either time-locking or rate-changes in the downstream nuclei. We find that Purkinje neuron synchrony is mainly represented by changes in the firing rate of cerebellar nuclei neurons. Pause beginning synchronization produced a unique effect on nuclei neuron firing, while the effect of pause ending and pause overlapping synchronization could not be distinguished from each other. Pause beginning synchronization produced better time-locking of nuclear neurons for short length pauses. We also characterize the effect of pause length and spike jitter on the nuclear neuron firing. Additionally, we find that the rate of rebound responses in nuclear neurons after a synchronous pause is controlled by the firing rate of Purkinje neurons preceding it.Peer reviewedFinal Published versio