Open and endovascular repair of the nontraumatic isolated aortic arch aneurysm

ObjectiveRepair of isolated aortic arch aneurysms (nontraumatic) by either open (OAR) or endovascular (TEVAR) methods is associated with need for hypothermic circulatory arrest, complex debranching procedures, or use of marginal proximal landing zones. This study evaluates outcomes for treatment of this cohort.MethodsOf 2153 patients undergoing arch repair (1993-2013), 137 (mean age, 60 years) were treated with isolated arch resection for nontraumatic aneurysms. Treatment was by open (n = 93), hybrid (n = 11), or TEVAR (n = 33) methods, with the last two approaches reserved for poor OAR candidates. Treatment was predominantly for saccular (n = 53) or fusiform (n = 30) aneurysms or dissection (n = 15). Rupture was present in 15%. Prior aortic repair was performed in the ascending (n = 30), arch (n = 40), descending (n = 24), or abdominal (n = 9) aorta. Propensity score adjustment was performed for multivariable analysis to account for baseline differences in patient groups as well as treatment selection bias.ResultsEarly mortality was seen in nine patients (7%). Morbidity included stroke (n = 9), paraplegia (n = 1), and need for dialysis (n = 5) or tracheostomy (n = 10). A composite outcome of death and stroke was independently predicted by advancing age (P = .055) and performance of a hybrid procedure (P = .012). The 15-year survival was 59%, with late mortality predicted by increasing age, presence of peripheral vascular disease, and perioperative stroke (all P < .05). The 10-year freedom from aortic rupture or reintervention was 75% and was higher after OAR (2-year OAR, 94% vs TEVAR or hybrid, 78%; P = .018). After propensity-adjusted Cox regression analysis, both prior abdominal aortic aneurysmectomy (P = .017) and an endovascular or hybrid procedure (P = .001) independently predicted late aortic rupture or need for reintervention.ConclusionsIsolated arch repair remains a high-risk procedure occurring frequently in the reoperative setting. Despite being performed in a higher risk group, endovascular strategies yielded similar outcomes but with an increased risk for aorta-related complications. These data support ongoing efforts to develop branched endografts specifically tailored for arch disease to potentially reduce morbidity related to currently available approaches

Influence of Mn dopants on InAs/GaAs quantum dot electronic states

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98664/1/ApplPhysLett_98_141907.pd

Gadolinium-enhanced magnetic resonance angiography of abdominal aortic aneurysms

AbstractPurpose: The objective of this study was to assess the usefulness of gadolinum-enhanced magnetic resonance angiography (MRA) for defining anatomic features relevant to performing aortic surgery for aneurysmal disease.Methods: Anatomic data defined by MRA, including abdominal aortic aneurysm (AAA) size and character, as well as the status of the celiac, mesenteric, renal, and iliac arteries, were correlated with angiography, ultrasonography, computed tomography, or operative data in 43 patients. Five MRA sequences were obtained in an hour-long examination optimized for aortoiliac, splanchnic, and renal artery imaging at 1.5 T in a body coil. Four of the sequences were performed during or after infusion of gadolinium to improve image quality.Results: MRA correctly defined the maximum aneurysm diameter, as well as its proximal and distal extent in all patients. MRA detected 33 of 35 significant stenoses among 153 splanchnic, renal, or iliac branches examined (sensitivity = 94% and specificity = 98%). MRA did not resolve the degree of aortic branch stenotic disease sufficiently to precisely grade its severity. MRA did not reliably define the status of the inferior mesenteric artery, lumbar arteries or internal iliac arteries. One ruptured AAA and one inflammatory AAA were correctly diagnosed by MRA. No patient had a contrast reaction or contrast-induced renal toxicity related to administration of gadolinium.Conclusion: Gadolinium-enhanced MRA of AAA provides appropriate, essential anatomic information for aortic reconstructive surgery in a 1-hour examination devoid of contrast-related renal toxicity or catheterization-related complications attending conventional arteriography. (J VASC SURG 1995;21:656-69.

Successful Angioplasty of a Superficial Femoral Artery StenosisCaused by a Suture-Mediated Closure Device

We report the successful angioplasty of an acutearterial narrowing after suture-mediated closure (SMC) of a femoralarterial puncture. A 75-year-old woman underwent a cerebral arteriogramvia a right common femoral artery puncture. The arteriotomy site wasclosed with a SMC device. Four days after placement the patientcomplained of pain in her right calf after walking. An arteriogram 7days after SMC showed a severe focal stenosis at the origin of thesuperficial femoral artery involving the presumed puncture site. Thelesion was successfully treated with balloon angioplasty. The patientat 6 months was asymptomatic.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41325/1/270_2003_Article_2649.pd

Controlling the Outcome of the Toll-Like Receptor Signaling Pathways

The Toll-Like Receptors (TLRs) are proteins involved in the immune system that increase cytokine levels when triggered. While cytokines coordinate the response to infection, they appear to be detrimental to the host when reaching too high levels. Several studies have shown that the deletion of specific TLRs was beneficial for the host, as cytokine levels were decreased consequently. It is not clear, however, how targeting other components of the TLR pathways can improve the responses to infections. We applied the concept of Minimal Cut Sets (MCS) to the ihsTLR v1.0 model of the TLR pathways to determine sets of reactions whose knockouts disrupt these pathways. We decomposed the TLR network into 34 modules and determined signatures for each MCS, i.e. the list of targeted modules. We uncovered 2,669 MCS organized in 68 signatures. Very few MCS targeted directly the TLRs, indicating that they may not be efficient targets for controlling these pathways. We mapped the species of the TLR network to genes in human and mouse, and determined more than 10,000 Essential Gene Sets (EGS). Each EGS provides genes whose deletion suppresses the network's outputs

Automatic Design of Synthetic Gene Circuits through Mixed Integer Non-linear Programming

Automatic design of synthetic gene circuits poses a significant challenge to synthetic biology, primarily due to the complexity of biological systems, and the lack of rigorous optimization methods that can cope with the combinatorial explosion as the number of biological parts increases. Current optimization methods for synthetic gene design rely on heuristic algorithms that are usually not deterministic, deliver sub-optimal solutions, and provide no guaranties on convergence or error bounds. Here, we introduce an optimization framework for the problem of part selection in synthetic gene circuits that is based on mixed integer non-linear programming (MINLP), which is a deterministic method that finds the globally optimal solution and guarantees convergence in finite time. Given a synthetic gene circuit, a library of characterized parts, and user-defined constraints, our method can find the optimal selection of parts that satisfy the constraints and best approximates the objective function given by the user. We evaluated the proposed method in the design of three synthetic circuits (a toggle switch, a transcriptional cascade, and a band detector), with both experimentally constructed and synthetic promoter libraries. Scalability and robustness analysis shows that the proposed framework scales well with the library size and the solution space. The work described here is a step towards a unifying, realistic framework for the automated design of biological circuits

Optimization in computational systems biology

Optimization aims to make a system or design as effective or functional as possible. Mathematical optimization methods are widely used in engineering, economics and science. This commentary is focused on applications of mathematical optimization in computational systems biology. Examples are given where optimization methods are used for topics ranging from model building and optimal experimental design to metabolic engineering and synthetic biology. Finally, several perspectives for future research are outlined

The Anti-Proliferative Effects of the CHFR Depend on the Forkhead Associated Domain, but not E3 Ligase Activity Mediated by Ring Finger Domain

The CHFR protein comprises fork head associated- (FHA) and RING-finger (RF) domain and is frequently downregulated in human colon and gastric cancers up to 50%. The loss of CHFR mRNA expression is a consequence of promoter methylation, suggesting a tumor suppressor role for this gene in gastrointestinal carcinogenesis. In terms of the biological functions of CHFR, it has been shown to activate cell cycle checkpoint when cells are treated with microtubule depolymerizing agents. Furthermore, CHFR was reported to have E3 ligase activity and promote ubiquitination and degradation of oncogenic proteins such as Aurora A and polo-like kinase 1. However, molecular pathways involved in the tumor suppressive function of CHFR are not yet clear since the two established roles of this protein are likely to inhibit cell growth. In this study, we have identified that the FHA domain of CHFR protein is critical for growth suppressive properties, whereas the RF and cysteine rich domains (Cys) are not required for this function. In contrast, the RF and Cys domains are essential for E3 ligase activity of CHFR. By the use of a cell cycle checkpoint assay, we also confirmed that the FHA domain of CHFR plays an important role in initiating a cell cycle arrest at G2/M, indicating a functional link exists between the anti-proliferative effects and checkpoint function of this tumor suppressor protein via this domain. Collectively, our data show that the checkpoint function of the FHA domain of CHFR is a core component of anti-proliferative properties against the gastrointestinal carcinogenesis