Redundant Loop Research Articles

Surgical management of cervical radiculopathy caused by redundant vertebral artery loop

In this article, the authors describe the case of a 27-year-old female presenting with a 2-year history of neck pain and radiculopathy attributable to compression of the right C-7 nerve root by tortuosity of the vertebral artery at the level of the C6-7 cervical foramina. An anterolateral approach to the transverse foramen was used to perform a vascular decompression to decompress the nerve root. The procedure was uneventful, and the patient woke up with almost all of her symptoms resolved. The authors also include a literature review of techniques performed in this setting, showing that multiple surgical approaches can be used and should be tailored to the patient symptoms and lesion characteristics.

Effect of positive feedback loops on the robustness of oscillations in the network of cyclin‐dependent kinases driving the mammalian cell cycle

The transitions between the G(1), S, G(2) and M phases of the mammalian cell cycle are driven by a network of cyclin-dependent kinases (Cdks), whose sequential activation is regulated by intertwined negative and positive feedback loops. We previously proposed a detailed computational model for the Cdk network, and showed that this network is capable of temporal self-organization in the form of sustained oscillations, which govern ordered progression through the successive phases of the cell cycle [Gérard and Goldbeter (2009) Proc Natl Acad Sci USA 106, 21643-21648]. We subsequently proposed a skeleton model for the cell cycle that retains the core regulatory mechanisms of the detailed model [Gérard and Goldbeter (2011) Interface Focus 1, 24-35]. Here we extend this skeleton model by incorporating Cdk regulation through phosphorylation/dephosphorylation and by including the positive feedback loops that underlie the dynamics of the G(1)/S and G(2)/M transitions via phosphatase Cdc25 and via phosphatase Cdc25 and kinase Wee1, respectively. We determine the effects of these positive feedback loops and ultrasensitivity in phosphorylation/dephosphorylation on the dynamics of the Cdk network. The multiplicity of positive feedback loops as well as the existence of ultrasensitivity promote the occurrence of bistability and increase the amplitude of the oscillations in the various cyclin/Cdk complexes. By resorting to stochastic simulations, we further show that the presence of multiple, redundant positive feedback loops in the G(2)/M transition of the cell cycle markedly enhances the robustness of the Cdk oscillations with respect to molecular noise.

Article Commentary: The Twisted Colon: A Review of Sigmoid Volvulus

Sigmoid volvulus (SV) is the third leading cause of colon obstruction in adults. In infants and children, it is exceedingly rare with only sporadic cases reported so far. SVs from secondary causes, with congenital megacolon being the most important, are nevertheless more common in young people. The etiology of this disorder is not completely understood. It is known to occur in the setting of redundant sigmoid loop, which rotates around its narrow and elongated mesentery. Although the latter occurs in the setting of constipation, a congenitally elongated colon, and other predisposing factors, there is no consensus on the precipitating factor leading to SV formation. The symptoms are suggestive of small bowel obstruction, but the presentations can be acute or indolent. Plain abdominal radiography is used to diagnose SV in most cases with computed tomography scan or magnetic resonance imaging as the confirmatory tests when necessary. After it has been untwisted, the definitive and standard therapy for SV is sigmoid resection and primary anastomosis. The nonresective alternatives have also been widely used with mixed success, but a large, randomized controlled trial is needed to compare their efficacy with resection and primary anastomosis. Laparoscopic surgery in SV management is unwarranted and costly. Complications of SV include hemorrhagic infarction, perforation, septic shock, and death. The mortality data from SV vary, but the latest literature cites an overall range of 14 to 45 per cent.

Percutaneous Insertion of Peritoneal Ports

To describe a technique for image-guided percutaneous insertion of peritoneal ports in patients without ascites who have undergone surgical debulking for stage III ovarian cancer. Between 2006 and 2010, 29 intraperitoneal ports were placed percutaneously in 29 patients who presented after debulking surgery for stage III ovarian cancer. Ultrasound and fluoroscopy guidance were used to assist in the port placement. We demonstrated a technical success rate of 100% in 29 patients. The ports remained in place for an average of 186 days; and during that time, only 2 complications (6.9%) arose. One patient presented with kinking and looping of the catheter/port reservoir connection, and the redundant loop was removed. The other patient presented with a suspected wound infection over the port pocket, and the port was removed. Placement of percutaneous intraperitoneal ports is feasible with an acceptably low complication rate of 6.9% in patients without abdominal ascites.

Construction and completion of flux balance models from pathway databases

Motivation: Flux balance analysis (FBA) is a well-known technique for genome-scale modeling of metabolic flux. Typically, an FBA formulation requires the accurate specification of four sets: biochemical reactions, biomass metabolites, nutrients and secreted metabolites. The development of FBA models can be time consuming and tedious because of the difficulty in assembling completely accurate descriptions of these sets, and in identifying errors in the composition of these sets. For example, the presence of a single non-producible metabolite in the biomass will make the entire model infeasible. Other difficulties in FBA modeling are that model distributions, and predicted fluxes, can be cryptic and difficult to understand.Results: We present a multiple gap-filling method to accelerate the development of FBA models using a new tool, called MetaFlux, based on mixed integer linear programming (MILP). The method suggests corrections to the sets of reactions, biomass metabolites, nutrients and secretions. The method generates FBA models directly from Pathway/Genome Databases. Thus, FBA models developed in this framework are easily queried and visualized using the Pathway Tools software. Predicted fluxes are more easily comprehended by visualizing them on diagrams of individual metabolic pathways or of metabolic maps. MetaFlux can also remove redundant high-flux loops, solve FBA models once they are generated and model the effects of gene knockouts. MetaFlux has been validated through construction of FBA models for Escherichia coli and Homo sapiens.Availability: Pathway Tools with MetaFlux is freely available to academic users, and for a fee to commercial users. Download from: biocyc.org/download.shtml.Contact: mario.latendresse@sri.comSupplementary information: Supplementary data are available at Bioinformatics online.

Iliac Artery Occlusion With “Oxbow Lake” Formation Following Stent Deployment in a Tortuous External Iliac Artery During EVAR

In this case report, we describe a complication that we term the "oxbow lake" deformity. This phenomenon occurs when a tortuous elongated external iliac artery segment is artificially straightened by an iliac stent resulting in kinking and compression of a redundant loop with lumen compromise. We describe the anatomy, corrective treatment, and outcome. This occurrence is potentially foreseeable with tortuous vascular anatomy and recognition can allow appropriate management planning avoiding complications for the patient.

Semialgebraic Regularization of Kinematic Loop Constraints in Multibody System Models

Redundant constraints in multibody system (MBS) models, reflected by a singular constraint Jacobian, impair the efficient dynamics simulation. In particular, kinematic loop constraints are often found to be permanently redundant. This problem is commonly attacked numerically by decomposing the constraint Jacobian either at every simulation time step or beforehand in an admissible assembly (assuming that the redundancy is permanent). This paper presents a method for the elimination of permanently redundant loop closure constraints, which, instead of numerically decomposing the constraints, relies on the geometric characterization of kinematic loops comprising lower kinematic pairs. In particular, the invariant vector space of velocities of a kinematic loop is taken into account, which can be determined as the sum of Lie (screw) algebras of two subchains of a kinematic loop. The actual reduction is achieved by restricting the constraints to this space. The presented method does not interfere with the actual generation of constraints but can be considered as a preprocessing step of MBS models. It is numerically robust and only uses a geometrically exact model. The method is able to completely eliminate redundant loop constraints for “nonparadoxical” single-loop mechanisms and applies conservatively to multiloop MBS. The presented method only requires information (vectors, matrices) that is readily available in any MBS simulation package. The only numerical operations involved are cross products and a singular value decomposition of a low dimensional matrix.

An Uncommon Ventricular Tachycardia due to Inactive PPM Lead

Our patient had recurrent syncope due to ventricular tachycardia (VT) after one year of VVI Pacemaker implantation. He had pacemaker pocket infection for which new pacemaker was implanted on opposite side but old lead was not explanted completely. Flouroscopy showed redundant loop of old lead in right ventricular inflow which was snared out subsequently. He never had syncope or VT after that.

Is it Time to Retire the A.V. Hill Model?

Recent publications by Emeritus Professor Roy Shephard propose that a "small group of investigators who have argued repeatedly (over the past 13 years) for a 'Central Governor'," should now either "Put up or shut up." Failing this, their 'hypothesis' should be 'consigned to the bottom draw for future reference'; but Professor Shephard's arguments are contradictory. Thus, in different sections of his article, Professor Shephard explains: why there is no need for a brain to regulate exercise performance; why there is no proof that the brain regulates exercise performance; and why the brain's proven role in the regulation of exercise performance is already so well established that additional comment and research is unnecessary. Hence, "The higher centres of an endurance athlete … call forth an initial effort … at a level where a minimal accumulation of lactate in the peripheral muscles is sensed." Furthermore, "a variety of standard texts have illustrated the many mutually redundant feedback loops (to the nervous system) that limit exercise." Yet, the figure from Professor Shephard's 1982 textbook does not contain any links between the nervous system, "many mutually redundant feedback loops" and skeletal muscle. This disproves his contradictory claims that although there is neither any need for, nor any proof of, any role of the brain in the regulation of exercise performance, the physiological mechanisms for this (non-existent) control were already well established in 1982. In contrast, the Central Governor Model (CGM) developed by our "small group … in a single laboratory" after 1998, provides a simple and unique explanation of how 'redundant feedback loops' can assist in the regulation of exercise behaviour. In this rebuttal to his article, I identify (i) the numerous contradictions included in Professor Shephard's argument; (ii) the real meaning of the facts that he presents; (iii) the importance of the evidence that he ignores; and (iv) the different philosophies of how science should be conducted according to either the Kuhnian or the Popperian philosophies of scientific discovery. My conclusion is that the dominance of an authoritarian Kuhnian philosophy, which refuses to admit genuine error or "the need to alter one's course of belief or action," explains why there is little appetite in the exercise sciences for the acceptance of genuinely novel ideas such as the CGM. Furthermore, to advance the case for the CGM, I now include evidence from more than 30 studies, which, in my opinion, can only be interpreted according to a model of exercise regulation where the CNS, acting in an anticipatory manner, regulates the exercise behaviour by altering skeletal muscle recruitment, specifically to ensure that homeostasis is maintained during exercise. Since few, if any, of those studies can be explained by the 'brainless' A.V. Hill Cardiovascular Model on which Professor Shephard bases his arguments, I argue that it is now the appropriate time to retire that model. Perhaps this will bring to an end the charade that holds either (i) that the brain plays no part in the regulation of exercise performance; or, conversely, (ii) that the role of the brain is already so well defined that further research by other scientists is unnecessary. However, this cannot occur in a discipline that is dominated by an authoritarian Kuhnian philosophy.

Chronic Vaccination with a Therapeutic EGF-Based Cancer Vaccine: A Review of Patients Receiving Long Lasting Treatment

Therapeutic vaccines continue to be one of the most active fields in cancer research. However, despite clear evidence of antitumor effect in laboratory animals, and despite the ability of current vaccine candidates to elicit tumor specific antibodies and T-cells in humans, objective responses in the clinical trials are rare. The role of therapeutic vaccines in advanced cancer patients, if any, would be to decrease the rate of disease progression and to increase survival and quality of life. Due to the redundant regulatory loops contracting the immune response to antigens that cannot be eliminated, such a role would require chronic vaccination, which is at first sight at odds with the classic experience of vaccinology. During the last decade our team has been developing a therapeutic vaccine for advanced lung cancer, which consists in human recombinant Epidermal Growth Factor (EGF) chemically conjugated to a carrier protein from Neisseria meningitides. Several clinical trials have been carried out, showing increase in anti-EGF antibody titters, decrease in plasma EGF concentration and survival advantage in vaccinated patients. In the present paper we review data from 58 patients who were vaccinated monthly for more than one or two years. Long term vaccination was feasible and safe, and there was no evidence of cumulative toxicity. Patients kept high anti-EGF antibody titters during all the time of vaccination, without evidence of immune response exhaustion. Continued vaccination increased the probability to get a high antibody response, which has been previously shown to be, in turn, associated with a better survival. Observations done in this series of patients suggest that long term therapeutic vaccination is a feasible strategy, worth to be further explored in the aim of transforming advanced cancer into a chronic disease.

Different effects of redundant feedback loops on a bistable switch

Bistable switches have important roles in cellular decision-making processes. Bistability can be the consequence of positive or double-negative feedback loops. Although necessary, such feedback is not sufficient for bistability, which also requires nonlinearity. Nonlinearity can be provided by synergy of multiple feedback loops or by an ultrasensitive response within a single feedback loop. However, these two possibilities are not mutually exclusive; a combination of them is also possible. Here we analyze a biochemical regulatory network that controls a crucial cell cycle transition in all eukaryotic cells and contains multiple redundant feedback loops and nonlinearity. We show in this realistic biological example that two redundant feedback loops have different effects on the position of one of the saddle-node bifurcations of the system, which determines where the system switches. This illustrates that even though the roles of positive and double-negative feedbacks have been regarded as equivalent, the difference in their architectures can lead to differences in their effects on the system. We speculate that this conclusion could be general for other bistable systems with redundant feedback loops.

Morphological Progression of Myelin Abnormalities in IgM-Monoclonal Gammopathy of Undetermined Significance Anti-Myelin-Associated Glycoprotein Neuropathy

To characterize the morphological progression of neuropathy associated with immunoglobulin M-monoclonal gammopathy of undetermined significance with anti-myelin-associated glycoprotein antibody, we assessed histopathologic features of sural nerve specimens from 15 patients, emphasizing widely spaced myelin (WSM), demyelination, and tomaculous changes. The frequency of WSM correlated with that of demyelination and tomaculous appearance in teased-fiber preparations. In longitudinal sections at nodes of Ranvier and paranodal regions, the spaces between terminal myelin loops, particularly those adjacent to the node of Ranvier, were widened, indicating an early change before demyelination, and there was concomitant swelling of terminal myelin loops. Some conspicuously swollen terminal myelin loops were detached from the paranodal axolemma, thereby widening the nodes of Ranvier. Tomacula coexisted frequently with redundant myelin loops and WSM, particularly in the outermost layer of myelin sheaths, suggesting that loosening of the outer layers contributes to their formation. By immunofluorescence microscopy, immunoglobulin M and myelin-associated glycoprotein were colocalized in paranodal regions and Schmidt-Lanterman incisures. Confocal analysis revealed colocalization of immunoglobulin M and complement product C3d corresponding to the area of WSM. Thus, morphological changes in terminal myelin loops, formation of WSM at paranodes, and subsequent dissociation from paranodal axolemma (which may be associated with activation of the complement pathway) likely contribute to demyelination in this condition. Loosening of compact myelin seems to contribute to tomacula formation.

An Innovative Matrix-Based Approach for Designing Product Variety

New product development (NPD) and innovation are key factors that affect a company’s long-term survival and growth. The design process is an important stage in new product development (NPD). Based on graph theory and the weighting concept , this paper presents a Quantified Design Structure Matrix (QDSM) which is a systematic planning method of optimizing design priorities and product architecture for managing product variety from an informational structure perspective. Focusing on product variety and the design process in concurrent engineering (CE), the planning model is divided into two phases: global planning and local planning. The proposed method helps designers optimize the design planning and plan better design strategies for product variety. A case study is used to illustrate this method. The results verify that designers may concurrently create variant design solutions in a product family that can meet different market needs without extra effort being spent on redundant design loops.

Foot pad skin biopsy in mouse models of hereditary neuropathy

Numerous transgenic and knockout mouse models of human hereditary neuropathies have become available over the past decade. We describe a simple, reproducible, and safe biopsy of mouse skin for histopathological evaluation of the peripheral nervous system (PNS) in models of hereditary neuropathies. We compared the diagnostic outcome between sciatic nerve and dermal nerves found in skin biopsy (SB) from the hind foot. A total of five animal models of different Charcot-Marie-Tooth neuropathies, and one model of congenital muscular dystrophy associated neuropathy were examined. In wild type mice, dermal nerve fibers were readily identified by immunohistochemistry, light, and electron microscopy and they appeared similar to myelinated fibers in sciatic nerve. In mutant mice, SB manifested myelin abnormalities similar to those observed in sciatic nerves, including hypomyelination, onion bulbs, myelin outfolding, redundant loops, and tomacula. In many strains, however, SB showed additional abnormalities—fiber loss, dense neurofilament packing with lower phosphorylation status, and axonal degeneration—undetected in sciatic nerve, possibly because SB samples distal nerves. SB, a reliable technique to investigate peripheral neuropathies in human beings, is also useful to investigate animal models of hereditary neuropathies. Our data indicate that SB may reveal distal axonal pathology in mouse models and permits sequential follow-up of the neuropathy in an individual mouse, thereby reducing the number of mice necessary to document pathology of the PNS. © 2010 Wiley-Liss, Inc.

Approach for tunneling the lead in deep brain stimulation

The implantation of a deep brain stimulator (DBS) is often a staged procedure that involves stereotactic placement of the neurostimulator electrode, followed by connection of the electrode to a pulse generator during a separate operation. The authors describe a practical technique for the retrograde tunneling of the stimulator lead during the initial electrode implantation procedure. After DBS electrode placement and securing of the lead, the lead is covered with a protective cap and boot, which are then folded back to tunnel a redundant loop of the lead in a retrograde fashion into a subgaleal pocket. This technique facilitates connection of the lead to the pulse generator connecting wire at the subsequent operation and may reduce lead damage.

Low-Power Soft Error Hardened Latch

This paper presents a low-power soft error-hardened latch suitable for reliable circuit operation. The proposed circuit uses redundant feedback loop to protect latch against soft error on the internal nodes, and transmission gate and Schmitt-trigger circuit to filter out transient resulting from particle hit on combinational logic. The proposed circuit has low power consumption with negative setup time and low timing overhead. The HSPICE post-layout simulation in 90nm CMOS technology reveals that circuit is able to recover from almost any single particle strike on internal nodes and tolerates input SETs up to 130ps of duration.

Remyelination in experimentally demyelinated connexin 32 KnockOut mice

The aim of this study was to evaluate the role of connexin 32 (Cx 32) during remyelination of the peripheral nervous system, through a local injection of either 0,1% ethidium bromide solution or saline in the sciatic nerve of Cx 32 knockout mice. Euthanasia was performed ranging from 1, 2, 3, 7, 15, 21 to 30 days after injection. Histochemical, immunohistochemical, immunofluorescence and transmission electron microscopical techniques were used to analyze the development of the lesions. Within the sciatic nerves, Schwann cells initially showed signs of intoxication and rejected their sheaths; after seven days, some thin newly formed myelin sheaths with uneven compactness and redundant loops (tomacula) were conspicuous. We concluded that the regeneration of lost myelin sheaths within the PNS followed the pattern already reported for this model in other laboratory species. Therefore, these results suggest that absence of Cx 32 did not interfere with the normal pattern of remyelination in this model in young mice.

A structural matrix-based modelling for designing product variety

The design process is an important stage in new product development. An information model is a useful tool for analysing and improving a complex design process and product architecture because it allows the designer to visualise information flow. Based on graph theory and the weighting concept, this paper presents a quantified design structure matrix, which is a systematic planning method of optimising design priorities and product architecture for managing product variety from an informational structure perspective. Focusing on product variety and the design process in concurrent engineering, the planning model is divided into two phases: global planning and local planning. The proposed method helps designers optimise design planning and plan better design strategies for product variety. It can be applied in developing future generations of a product based on an existing product. A case study is used to illustrate this method. The results verify that designers can concurrently create variant design solutions in a product family that can meet different market needs without extra effort being spent on redundant design loops.

Current state of double balloon endoscopy: The latest approach to small intestinal diseases

Recent developments of capsule endoscopy and double balloon endoscopy (DBE) have made endoscopic examination of the entire small bowel practical, and changed the diagnostic algorithm for small bowel diseases. Double balloon endoscopy uses two balloons, one attached to the tip of the endoscope and another at the distal end of an overtube. By using these balloons to grip the intestinal wall, the endoscope can be inserted further without forming redundant loops of intestine. Total inspection by DBE is usually achieved by combination of sequential oral and anal intubations; success rates are reported to be 40-80%. Indications for DBE include scrutiny for obscure gastrointestinal bleeding, small bowel tumor, small bowel stricture and following up evaluation of previously diagnosed small bowel diseases. Because DBE has an accessory channel and good maneuverability in the distal small intestine, it enables endoscopic treatment, including hemostasis, balloon dilation, polypectomy, mucosal resection, retrieval of foreign bodies and endoscopic retrograde cholangiopancreatography (in the case of post-operative anastomoses). Double balloon endoscopy is also useful for cases of difficult colonoscopy, providing success rates of total colonoscopy between 88-100%. Although it has been a few years since its development, the usefulness of DBE is now well recognized. This challenging procedure has become popular rapidly and is currently used in many countries.

Diagnostic Yield and Therapeutic Impact of Single Balloon Enteroscopy; A Series of 60 Patients with Suspected Small Bowel Disease

Introduction: Non surgical management of small intestinal diseases is difficult due to lack of proper instruments to access the long redundant bowel loops. Single balloon enteroscopy (SBE) is novel method of push and pull enteroscopy which allows deep intubation of intestine. Aim: Single-center prospective study conducted from February 2007 to October 2007, to evaluate the clinical utility of the prototype SBE system. Methods: Subjects with suspected small bowel disease who required deep enteroscopy were enrolled. The Olympus XSIF-Q260Y enteroscope [200 cm length,9.2 mm outer diameter (OD), and 2.8 mm working channel] was coupled with a 132 cm long,13.2 mm OD single use silicon overtube, which has a balloon at the distal end. Balloon is operated with Olympus balloon control unit (MAJ 1440). The tip of the enteroscope has a broad bending capability due to its extreme flexibility allowing anchorage to the small bowel thus facilitating deep intubation. Depth of insertion was determined by carefully recording length of the scope inserted during each pull and push maneuver. Fluoroscopy was utilized intermittently. Enteroscopy was done under monitored anesthesia care (Midazolam, Propofol). All patients underwent antegrade enteroscopic examination, 10 underwent both antegrade and retrograde procedures, with tattooing during the initial procedure to confirm a total small-bowel examination. Results: A total of 60 subjects (36M /24F, mean age 39.83 ± 14.66 Years) were studied. Indications for SBE included obscure GI bleeding(18),chronic abdominal pain with abnormal imaging studies like Barium series, CTscan etc (21), malabsorption Syndrome (11), Polyposis syndromes (9) and Foreign body (1). Mean procedure time was 63 ± 18 min. The mean depth of insertion was 260 ± 60 cms beyond ligament of Treitz. Pan-enteroscopy was possible in 5 out of 10 cases. Enteroscopic findings were arteriovenous malformations [AVMs] (7), ulcers (15), polyps (6), diffuse enteritis (2), mass lesion (3) and effacement of jejunal folds (3). Histological diagnosis included adenocarcinoma (3), Crohn's disease (4), Tuberculosis (2), Strongyloidosis (2), Giardiasis (1), Amyloidosis (1), Celiac Sprue (4), Tropical sprue(1), Hamartomatous polyps (4) and non specific ulcers(9). Diagnostic yield in cases of obscure G I bleed, chronic abdominal pain and malabsorption syndrome were 77%, 61% and 63% respectively. Therapeutic interventions included Argon plasma coagulation of bleeding ulcers and AVMs (12), Polypectomy (3) and foreign body removal (1). No complications were encountered. Conclusion-The Olympus single balloon enteroscope was well-tolerated and led to a high diagnostic and therapeutic yield in cases of small bowel disorders.