bluuebunny/crossref_metadata_2025 huggingface dataset:
BISTABILITY AND LONG-TERM CURE IN A WITHIN-HOST MODEL OF HEPATITIS C
Authors: DEBROY SWATI , BOLKER BENJAMIN M. , MARTCHEVA MAIA
Published: December 2011

Treatment of hepatitis C virus (HCV) is lengthy, expensive and fraught with side-effects, succeeding in only 50% of treated patients. In clinical settings, short-term treatment response (so-called sustained virological response (SVR)) is used to predict prolonged viral suppression. Although ordinary differential equation (ODE) models for within-host HCV infection have illuminated the mechanisms underlying treatment with interferon (IFN) and ribavirin (RBV), they have difficulty producing SVR without the introduction of an external extinction threshold. Here we show that bistability in an existing ODE model of HCV, which occurs when infected hepatocytes proliferate sufficiently faster than uninfected hepatocytes, can produce SVR without an external extinction threshold under biologically relevant conditions. The model can produce all clinically observed patient profiles for realistic parameter values; it can also be used to estimate the efficacy and/or duration of treatment that will ensure permanent cure for a particular patient.
PREDICTING THE PROBABILITY OF PERSISTENCE OF HIV INFECTION WITH THE STANDARD MODEL
Authors: TUCKWELL HENRY C. , SHIPMAN PATRICK D.
Published: December 2011

It is not well understood why the transmission of HIV may have a small probability of occurrence despite frequent high risk exposures or ongoing contact between members of a discordant couple. We explore the possible contributions made by distributions of system parameters beginning with the standard three-component differential equation model for the growth of a HIV virion population in an infected host in the absence of drug therapy. The overall dynamical behavior of the model is determined by the set of values of six parameters, some of which describe host immune system properties and others which describe virus properties. There may be one or two critical points whose natures play a key role in determining the outcome of infection and in particular whether the HIV population will persist or become extinct. There are two cases which may arise. In the first case, there is only one critical point P1at biological values and this is an asymptotically stable node. The system ends up with zero virions and so the host becomes HIV-free. In the second case, there are two critical points P1and P2at biological values. Here P1is an unstable saddle point and P2is an asymptotically stable spiral point with a non-zero virion level. In this case the HIV population persists unless parameters change. We let the parameter values take random values from distributions based on empirical data, but suitably truncated, and determine the probabilities of occurrence of the various combinations of critical points. From these simulations the probability that an HIV infection will persist, across a population, is estimated. It is found that with conservatively estimated distributions of parameters, within the framework of the standard 3-component model, the chances that a within-host HIV population will become extinct is between 0.6% and 6.9%. With less conservative parameter estimates, the probability is estimated to be as high as 24%. The many complicating factors related to the transmission and possible spontaneous elimination of the virus and the need for experimental data to clarify whether transient infections may occur are discussed. More realistic yet complicated higher dimensional models are likely to yield smaller probabilities of extinction.
A MINIMAL MODEL FOR ECOEPIDEMICS WITH GROUP DEFENSE
Authors: VENTURINO EZIO
Published: December 2011

The new idea of group defense as recently introduced by the author in the context of two interacting populations is in this paper applied to communities subject also to a disease. The system is formulated with the bare minimum of interactions among all the populations involved in order to highlight the effects of the nonlinearity describing the defense mechanism. A key parameter identified in the purely demographic model, which completely describes its outcomes, is seen here to have an important role also, in that it is dropping below a threshold prevents the disease from invading the environment and causes the healthy prey and predators to coexist via persistent oscillations.
A CAPACITIVE MEMs VERILOGA-BASED SENSOR SYSTEM FOR BUILDING INTEGRITY MONITORING
Authors: SANTANA JUAN , VAN DEN HOVEN RICHARD
Published: December 2011

A capacitive MEMS Ultra-Low-Power readout for accelerometers and strain sensors using VerilogA models is presented. The VerilogA model of the accelerometers and strain sensors allows the simulation of a system in a half-bridge configuration. The gain of the system is controlled by integrating pulses from the excitation voltage which accurately controls the Signal-to-Noise ratio. A Figure-of-Merit of [Formula: see text] was achieved for a sensor range of ±2.0 g and ±20,000 με over a 100 Hz bandwidth. Residual motion artefacts are also canceled by the system.
SYNTHESIS OF UNIFORM LINEAR ANTENNA ARRAY USING GENETIC ALGORITHM WITH COST BASED ROULETTE TO MAXIMIZE SIDELOBE LEVEL REDUCTION
Authors: LASEETHA T. S. JEYALI , SUKANESH R.
Published: December 2011

This paper discusses the deployment of Genetic Algorithm optimization method for the synthesis of antenna array radiation pattern in adaptive beamforming. The synthesis problem discussed is to find the weights of the Uniform Linear Antenna array elements that are optimum to provide the radiation pattern with maximum reduction in the sidelobe level. This technique proved its effectiveness in improving the performance of the antenna array.
QVM
Authors: Arnold Matthew , Vechev Martin , Yahav Eran
Published: December 2011

Coping with software defects that occur in the post-deployment stage is a challenging problem: bugs may occur only when the system uses a specific configuration and only under certain usage scenarios. Nevertheless, halting production systems until the bug is tracked and fixed is often impossible. Thus, developers have to try to reproduce the bug in laboratory conditions. Often, the reproduction of the bug takes most of the debugging effort.

In this paper we suggest an approach to address this problem by using a specialized runtime environment called
Quality Virtual Machine
(QVM). QVM efficiently detects defects by continuously monitoring the execution of the application in a production setting. QVM enables the efficient checking of violations of user-specified correctness properties, that is, typestate safety properties, Java assertions, and heap properties pertaining to ownership. QVM is markedly different from existing techniques for continuous monitoring by using a novel overhead manager which enforces a user-specified overhead budget for quality checks. Existing tools for error detection in the field usually disrupt the operation of the deployed system. QVM, on the other hand, provides a balanced trade-off between the cost of the monitoring process and the maintenance of sufficient accuracy for detecting defects. Specifically, the overhead cost of using QVM instead of a standard JVM, is low enough to be acceptable in production environments.

We implemented QVM on top of IBM’s J9 Java Virtual Machine and used it to detect and fix various errors in real-world applications.
How Well Do Search Engines Support Code Retrieval on the Web?
Authors: Sim Susan Elliott , Umarji Medha , Ratanotayanon Sukanya , Lopes Cristina V.
Published: December 2011

Software developers search the Web for various kinds of source code for diverse reasons. In a previous study, we found that searches varied along two dimensions: the size of the search target (e.g., block, subsystem, or system) and the motivation for the search (e.g., reference example or as-is reuse). Would each of these kinds of searches require different search technologies? To answer this question, we conducted an experiment with 36 participants to evaluate three diverse approaches (general purpose information retrieval, source code search, and component reuse), as represented by five Web sites (Google, Koders, Krugle, Google Code Search, and SourceForge). The independent variables were search engine, size of search target, and motivation for search. The dependent variable was the participants judgement of the relevance of the first ten hits. We found that it was easier to find reference examples than components for as-is reuse and that participants obtained the best results using a general-purpose information retrieval site. However, we also found an interaction effect: code-specific search engines worked better in searches for subsystems, but Google worked better on searches for blocks. These results can be used to guide the creation of new tools for retrieving source code from the Web.
Evolving 3D objects with a generative encoding inspired by developmental biology
Authors: Clune Jeff , Lipson Hod
Published: December 2011

This paper introduces an algorithm for evolving 3D objects with a generative encoding that abstracts how biological morphologies are produced. Evolving interesting 3D objects is useful in many disciplines, including artistic design (e.g. sculpture), engineering (e.g. robotics, architecture, or product design), and biology (e.g. for investigating morphological evolution). A critical element in evolving 3D objects is the representation, which strongly influences the types of objects produced. In 2007 a representation was introduced called Compositional Pattern Producing Networks (CPPN), which abstracts how natural phenotypes are generated. To date, however, the ability of CPPNs to create 3D objects has barely been explored. Here we present a new way to create 3D objects with CPPNs. Experiments with both interactive and target-based evolution demonstrate that CPPNs show potential in generating interesting, complex, 3D objects. We further show that changing the information provided to CPPNs and the functions allowed in their genomes biases the types of objects produced. Finally, we validate that the objects transfer well from simulation to the real-world by printing them with a 3D printer. Overall, this paper shows that evolving objects with encodings based on concepts from biological development can be a powerful way to evolve complex, interesting objects, which should be of use in fields as diverse as art, engineering, and biology.
Robust Design Optimization of an Aerospace Vehicle Prolusion System
Authors: Raza Muhammad Aamir , Liang Wang
Published: December 2011

This paper proposes a robust design optimization methodology under design uncertainties of an aerospace vehicle propulsion system. The approach consists of 3D geometric design coupled with complex internal ballistics, hybrid optimization, worst‐case deviation, and efficient statistical approach. The uncertainties are propagated through worst‐case deviation using first‐order orthogonal design matrices. The robustness assessment is measured using the framework of mean‐variance and percentile difference approach. A parametric sensitivity analysis is carried out to analyze the effects of design variables variation on performance parameters. A hybrid simulated annealing and pattern search approach is used as an optimizer. The results show the objective function of optimizing the mean performance and minimizing the variation of performance parameters in terms of thrust ratio and total impulse could be achieved while adhering to the system constraints.
Global Properties of Virus Dynamics Models with Multitarget Cells and Discrete‐Time Delays
Authors: Elaiw A. M. , Alghamdi M. A.
Published: December 2011

We propose a class of virus dynamics models with multitarget cells and multiple
intracellular delays and study their global properties. The first model is a 5‐dimensional system of nonlinear delay differential equations (DDEs) that describes the interaction of the virus with two classes of target cells. The second model is a (2n + 1)‐dimensional system of nonlinear DDEs that describes the dynamics of the virus, n classes of uninfected target cells, and n classes of infected target cells. The third model generalizes the second one by assuming that the incidence rate of infection is given by saturation functional response. Two types of discrete time delays are incorporated into these models to describe (i) the latent period between the time the target cell is contacted by the virus particle and the time the virus enters the cell, (ii) the latent period between the time the virus has penetrated into a cell and the time of the emission of infectious (mature) virus particles. Lyapunov functionals are constructed to establish the global asymptotic stability of the uninfected and infected steady states of these models. We have proven that if the basic reproduction number R0 is less than unity, then the uninfected steady state is globally asymptotically stable, and if R0 > 1 (or if the infected steady state exists), then the infected steady state is globally asymptotically stable.
Epiphyseal Fracture of the Coracoid Process Occurring at the Conjoined Tendon Origin
Authors: Nakama Kenjiro , Gotoh Masafumi , Mitsui Yasuhiro , Okawa Takahiro , Higuchi Fujio , Nagata Kensei
Published: December 2011

Fracture of the coracoid process is uncommon, and most previous studies have reported this fracture occurring in association with direct trauma to the shoulder or transmission of force from the upper arm or elbow (Ada and Miller 1991, Benton and Nelson 1971, Eyres et al. 1995). We present a case in which epiphyseal fracture occurred at the origin of the conjoined tendon following excessive muscle contraction. We believe this represents the first description of such a method of injury.
Millimeterwave Spectral Studies of Propynal (HCCCHO) Produced by DC Glow Discharge and Ab Initio DFT Calculation
Authors: Jaman A. I. , Bhattacharya Rangana , Mandal Debasish , Das Abhijit K.
Published: December 2011

The ground-state (v=0) millimeterwave rotational spectrum of propynal (HCCCHO) produced by a DC glow discharge through a low-pressure (~10–20 mTorr) flow of propargyl alcohol (HCCCH2OH) vapor has been observed in the frequency region: 36.0–94.0 GHz. Measured rotational transition frequencies along with the previously reported microwave and millimeterwave transitions were fitted to a standard asymmetric-top Hamiltonian to determine an improved set of rotational and centrifugal distortion constant. Detailed DFT calculations were also carried out with various functional and basis sets to evaluate the spectroscopic constants, dipole moment, and various structural parameters of propynal and compared with the corresponding experimental values.
Mechanisms of Oxidation‐Reduction Reactions Can Be Predicted by the Magnetic Isotope Effect
Authors: Epov Vladimir N.
Published: December 2011

Magnetic isotope effect can cause mass‐independent isotope fractionation, which can be used to predict the mechanisms of chemical reactions. In this critical paper, the isotope fractionation caused by magnetic isotope effect is used to understand detailed mechanisms of oxidation‐reduction reactions for some previously published experimental data. Due to the rule that reactions are allowed for certain electron spin state, and forbidden for others, magnetic isotopes show chemical anomalies during these reactions due to the hyperfine interaction of the nuclear spin with the electron spin. It is demonstrated that compound or complex in paramagnetic (triplet) state accepts electrons during the reactions of electron transfer. Also, ligand field strength is responsible for the magnitude and the sign of the mass‐independent fractionation. From another side, magnetic isotope effect can be used to predict the ligand strength. According to the proposed mechanism, the following parameters are important for the sign and magnitude of mass‐independent isotope fractionation caused by magnetic isotope effect (due to predominant either singlet‐triplet or triplet‐singlet evolution): (i) the arrangement of the ligands around the metal ion; (ii) the nature (strength) of the ligands surrounding the metal ion; (iii) presence/absence of light. The suggested approach is applied to understand Hg reduction by dissolved organic carbon or by Sn(II).
A Rare Cause of Cyanosis: Hepatopulmonary Syndrome Caused by Congenital Extrahepatic Portosystemic Shunt
Authors: Ding Xue-Yan , Chen Feng , Zhao Xian-Xian , Wu Hong , Chen Shao-Ping , Qin Yong-Wen
Published: December 2011

A 19-year-old male patient presented cyanosis and dyspnoea because of the presence of multiple pulmonary arteriovenous fistulas resulting in oxygen desaturation. The CTA revealed that intestinal and splenic venous blood bypasses the liver and drains into the inferior vena cava. This is the first reported case of hepatopulmonary syndrome caused by congenital extrahepatic portosystemic shunt in which intestinal and splenic venous blood bypasses the liver and drains into the inferior vena cava.
Solving Advection Equations by Applying the Crank‐Nicolson Scheme Combined with the Richardson Extrapolation
Authors: Zlatev Zahari , Dimov Ivan , Faragó István , Georgiev Krassimir , Havasi Ágnes , Ostromsky Tzvetan
Published: December 2011

Advection equations appear often in large‐scale mathematical models arising in many fields of science and engineering. The Crank‐Nicolson scheme can successfully be used in the numerical treatment of such equations. The accuracy of the numerical solution can sometimes be increased substantially by applying the Richardson Extrapolation. Two theorems related to the accuracy of the calculations will be formulated and proved in this paper. The usefulness of the combination consisting of the Crank‐Nicolson scheme and the Richardson Extrapolation will be illustrated by numerical examples.
Stroke Rehabilitation in Frail Elderly with the Robotic Training Device ACRE: A Randomized Controlled Trial and Cost-Effectiveness Study
Authors: Schoone M. , Dusseldorp E. , van den Akker-van Marle M. E. , Doornebosch A. J. , Bal R. , Meems A. , Oderwald M. P. , van Balen R.
Published: December 2011

The ACRE (ACtive REhabilitation) robotic device is developed to enhance therapeutic treatment of upper limbs after stroke. The aim of this study is to assess effects and costs of ACRE training for frail elderly patients and to establish if ACRE can be a valuable addition to standard therapy in nursing home rehabilitation. The study was designed as randomized controlled trial, one group receiving therapy as usual and the other receiving additional ACRE training. Changes in motor abilities, stroke impact, quality of life and emotional well-being were assessed. In total, 24 patients were included. In this small number no significant effects of the ACRE training were found. A large number of 136 patients were excluded. Main reasons for exclusion were lack of physiological or cognitive abilities. Further improvement of the ACRE can best be focused on making the system suitable for self-training and development of training software for activities of daily living.
Treatment of Acute Pelvic Inflammatory Disease
Authors: Sweet Richard L.
Published: December 2011

Pelvic inflammatory disease (PID), one of the most common infections in nonpregnant women of reproductive age, remains an important public health problem. It is associated with major long-term sequelae, including tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. In addition, treatment of acute PID and its complications incurs substantial health care costs. Prevention of these long-term sequelae is dependent upon development of treatment strategies based on knowledge of the microbiologic etiology of acute PID. It is well accepted that acute PID is a polymicrobic infection. The sexually transmitted organisms,Neisseria gonorrhoeaeandChlamydia trachomatis, are present in many cases, and microorganisms comprising the endogenous vaginal and cervical flora are frequently associated with PID. This includes anaerobic and facultative bacteria, similar to those associated with bacterial vaginosis. Genital tract mycoplasmas, most importantlyMycoplasma genitalium, have recently also been implicated as a cause of acute PID. As a consequence, treatment regimens for acute PID should provide broad spectrum coverage that is effective against these microorganisms.
Pathological Findings and Distribution of Pandemic Influenza A (H1N1) 2009 Virus in Lungs from Naturally Infected Fattening Pigs in Norway
Authors: Valheim Mette , Gamlem Hans , Gjerset Britt , Germundsson Anna , Lium Bjørn
Published: December 2011

The Norwegian pig population was considered free from influenza A virus infections until the first case of porcine pandemic influenza A (H1N1) 2009 virus infection in October 2009. Human to pig transmission of virus was suspected. Unusual lung lesions were observed in fattening pigs, with red, lobular, multifocal to coalescing consolidation, most frequently in the cranial, middle, and accessory lobes. The main histopathological findings were epithelial degeneration and necrosis, lymphocyte infiltration in the epithelial lining and lamina propria of small bronchi and bronchioles, and peribronchial and peribronchiolar lymphocyte infiltrations. Infection with pandemic influenza A (H1N1) 2009 virus was confirmed by real-time RT-PCR and immunohistochemical detection of influenza A virus nucleoprotein in the lesions. This investigation shows that natural infection with the pandemic influenza A (H1N1) 2009 virus induces lung lesions similar to lesions described in experimental studies and natural infections with other swine-adapted subtypes of influenza A viruses.
Vortex Streets on a Sphere
Authors: Alobaidi Ghada , Mallier Roland
Published: December 2011

We consider flows on a spherical surface and use a transformation to transport some well‐known periodic two‐dimensional vortex streets to that spherical surface to arrive at some new expressions for vortex streets on a sphere.
Asymptotic Analysis of Transverse Magnetic Multiple Scattering by the Diffraction Grating of Penetrable Cylinders at Oblique Incidence
Authors: Kavaklıoğlu Ömer , Lang Roger Henry
Published: December 2011

We have presented a derivation of the asymptotic equations for transverse magnetic multiple scattering coefficients of an infinite grating of penetrable circular cylinders for obliquely incident plane electromagnetic waves. We have first deducted an “Ansatz” delineating the asymptotic behavior of the transverse magnetic multiple scattering coefficients associated with the most generalized condition of oblique incidence (Kavaklıoğlu, 2000) by exploiting Schlömilch series corresponding to the special circumstance that the grating spacing is much smaller than the wavelength of the incident electromagnetic radiation. The validity of the asymptotic equations for the aforementioned scattering coefficients has been verified by collating them with the Twersky′s asymptotic equations at normal incidence. Besides, we have deduced the consequences that the asymptotic forms of the equations at oblique incidence acquired in this paper reduce to Twersky′s asymptotic forms at normal incidence by expanding the generalized scattering coefficients at oblique incidence into an asymptotic series as a function of the ratio of the cylinder radius to the grating spacing.
Pulmonary Effects of Neonatal Hydrocortisone Treatment in Ventilator-Dependent Preterm Infants
Authors: de Jong Sandra E. A. , Groenendaal Floris , van Bel Frank , Rademaker Karin J.
Published: December 2011

Background/Objective. Hydrocortisone, administered to ventilated preterm neonates to facilitate extubation, has no adverse long-term effects, but short-term pulmonary effects have not been described previously. In the present study, we analyzed effects of hydrocortisone on ventilator settings and FiO2in ventilator-dependent preterm infants.Patients and Methods. Fifty-five preterm children were included in this retrospective cohort study. Hydrocortisone was administered at a postnatal age of > 7 days to treat chronic lung disease (CLD). Ventilator settings before and after hydrocortisone administration were recorded as well as FiO2at 36 weeks' gestational age. Presence of cerebral palsy was assessed at a mean corrected age of 24.1 months.Results. Hydrocortisone administered at a median postnatal age of 14 days significantly reduced FiO2from a median of 0.39 to 0.30, mean airway pressure (MAP) from a median of 10.0 cm H2O to 7.6 cm H2O, and PaCO2from a median of 53.5 mmHg to 47 mmHg. Extubation was achieved in all patients. CLD at 36 weeks was present in 11 of the 52 patients (21.1%). None developed cerebral palsy.Conclusions. Hydrocortisone was effective in reducing the FiO2, MAP, and PaCO2and facilitated extubation. Hydrocortisone was not associated with cerebral palsy.
Self-Reconfigurable Modular Robots Adaptively Transforming a Mechanical Structure: Algorithm for Adaptive Transformation to Load Condition
Authors: Suzuki Yosuke , Inou Norio , Kimura Hitoshi , Koseki Michihiko
Published: December 2011

Self-reconfigurable modular robots are composed of modules which are able to autonomously change the way they are connected. An appropriate control algorithm enables the modular robots to change their shape in order to adapt to their immediate environment. In this paper, we propose an algorithm for adaptive transformation to load condition of the modular robots. The algorithm is based on a simple idea that modules have tendency to gather around stress-concentrated parts and reinforce the parts. As a result of the self-reconfiguration rule, the modular robots form an appropriate structure to stand for the load condition. Applying the algorithm to our modular robot named “CHOBIE II,” we show by computer simulation that the modules are able to construct a cantilever structure with avoiding overstressed states.
Novel Insights into the Role of Caveolin-2 in Cell- and Tissue-Specific Signaling and Function
Authors: Sowa Grzegorz
Published: December 2011

Caveolin-2 is one of the major protein components of cholesterol- and glycosphingolipid-rich flask-shaped invaginations of plasma membrane caveolae. A new body of evidence suggests that caveolin-2 plays an important, and often more direct, role than caveolin-1 in regulating signaling and function in a cell- and tissue type-specific manner. The purpose of this paper is to primarily focus on discussing how these recent discoveries may help better understand the specific contribution of caveolin-2 to lipid raft- and caveolae-regulated cell/tissue-specific signaling and functions.
Cochlear Implantation after Bacterial Meningitis in Infants Younger Than 9 Months
Authors: Roukema B. Y. , Van Loon M. C. , Smits C. , Smit C. F. , Goverts S. T. , Merkus P. , Hensen E. F.
Published: December 2011

Objective. To describe the audiological, anesthesiological, and surgical key points of cochlear implantation after bacterial meningitis in very young infants.Material and Methods. Between 2005 and 2010, 4 patients received 7 cochlear implants before the age of 9 months (range 4–8 months) because of profound hearing loss after pneumococcal meningitis.Results. Full electrode insertions were achieved in all operated ears. The audiological and linguistic outcome varied considerably, with categories of auditory performance (CAP) scores between 3 and 6, and speech intelligibility rating (SIR) scores between 0 and 5. The audiological, anesthesiological, and surgical issues that apply in this patient group are discussed.Conclusion. Cochlear implantation in very young postmeningitic infants is challenging due to their young age, sequelae of meningitis, and the risk of cochlear obliteration. A swift diagnostic workup is essential, specific audiological, anesthesiological, and surgical considerations apply, and the outcome is variable even in successful implantations.
Inadvertent Percutaneous Endoscopic Gastrostomy Tube Placement through the Transverse Colon to the Stomach Causing Intractable Diarrhea: A Case Report
Authors: Burke David T. , Geller Andrew I. , Carayannopoulos Alexios G. , Goldstein Richard
Published: December 2011

Background. Among patients with chronic disease, percutaneous endoscopic gastrostomy (PEG) tubes are a common mechanism to deliver enteral feedings to patients unable to feed by mouth. While several cases in the literature describe difficulties with and complications of the initial placement of the PEG, few studies have documented the effects of a delayed diagnosis of a misplaced tube.Methods. This case study reviews the hospitalization of an 82 year old male with an inadvertent placement of a PEG tube through the transverse colon. Photos of the placement in the stomach as well as those of the follow up colonoscopy, and a recording of the episodes of diarrhea during the hospitalization were made.Results. The records of this patient reveal complaints of gastrointestinal distress and diarrhea immediately after placement of the tube. Placement in the stomach was verified by endoscopy, with discovery of the tube only after a follow up colonoscopy. The tube remained in place after this discovery, and was removed weeks after the diarrhea was unsuccessfully treated with antibiotics. After tube removal, the patient recovered well and was sent home.
Unusual Presentation of Phacolytic Glaucoma: Simulating Microbial Keratitis
Authors: Sahu Srikant Kumar , Keswarwani Siddharth , Mittal Ruchi
Published: December 2011

The differential diagnoses for phacolytic glaucoma are acute angle closure glaucoma, open angle glaucoma with uveitis, neovascular glaucoma, and glaucoma secondary to trauma. We report an unusual case where the dislocated cataractous lens firmly adherent to the corneal endothelium evoked a cellular reaction similar to phacolytic glaucoma but clinically appeared like a deep corneal abscess. The 73-year-old lady presented with severe photophobia, pain, and redness in the left eye for two months despite being on antibiotics and antifungals. Anterior chamber wash revealed a cataractous lens buried within the infiltrate, which was removed and sent for histopathological examination. Postoperatively she was treated with topical ofloxacin, homatropine, dorzolamide, timolol, and tapering dose of steroids. Histological confirmation of inflammation, histiocytic response, and giant cells around the lens material confirmed the ongoing phacolytic process. Photophobia, pain, and redness subsided following removal of the lens and surrounding cellular reaction. At her last visit, four months after surgery, she was comfortable.
Interstitial Lung Disease in Rheumatoid Arthritis in the Era of Biologics
Authors: Picchianti Diamanti A. , Germano V. , Bizzi E. , Laganà B. , Migliore A.
Published: December 2011

Interstitial lung disease (ILD) represents a severe manifestation in connective tissue diseases (CTD), with an overall incidence of 15%, and it is still a challenge for clinicians evaluation and management. ILD is the most common manifestation of lung involvement in Rheumatoid Arthritis (RA), observed in up to 80% of biopsies, 50% of chest Computed Tomography (CT) and only 5% of chest radiographs. Histopatological patterns of ILD in RA may present with different patterns, such as: usual interstitial pneumonia, non specific interstitial pneumonia, desquamative interstitial pneumonia, organizing pneumonia, and eosinophilic infiltration. The incidence of ILD in RA patients is not only related to the disease itself, many drugs may be in fact associated with the development of pulmonary damage. Some reports suggest a causative role for TNFαinhibitors in RA-ILD development/worsening, anyway, no definitive statement can be drawn thus data are incomplete and affected by several variables. A tight control (pulmonary function tests and/or HRCT) is mandatory in patients with preexisting ILD, but it should be also performed in those presenting risk factors for ILD and mild respiratory symptoms. Biologic therapy should be interrupted, and, after excluding triggering infections, corticosteroids should be administered.
Retinal Vascular Tortuosity in a Patient with Weill-Marchesani Syndrome
Authors: Gallagher Kevin , Salam Tahrina , Sin Barron , Gupta Sandy , Zambarakji Hadi
Published: December 2011

Weill-Marchesani syndrome (WMS) is a rare connective tissue disorder with characteristic phenotypic skeletal and ocular manifestations. A 28-year-old myopic female presented with an 8-month history of bilateral blurred vision. On examination, she was noted to be of short stature with brachydactyly. On ocular examination, she was found to be spherophakic with bilateral inferiorly subluxated lenses. Serum and urine homocysteine were normal and a syphilis screen was negative. A diagnosis of Weill-Marchesani syndrome was made. Fundoscopy revealed bilateral tortuous retinal vessels. We report the first illustrated case of retinal vascular tortuosity as an ocular manifestation of Weill-Marchesani syndrome.
A Probability Collectives Approach with a Feasibility‐Based Rule for Constrained Optimization
Authors: Kulkarni Anand J. , Tai K.
Published: December 2011

This paper demonstrates an attempt to incorporate a simple and generic constraint handling technique to the Probability Collectives (PC) approach for solving constrained optimization problems. The approach of PC optimizes any complex system by decomposing it into smaller subsystems and further treats them in a distributed and decentralized way. These subsystems can be viewed as a Multi‐Agent System with rational and self‐interested agents optimizing their local goals. However, as there is no inherent constraint handling capability in the PC approach, a real challenge is to take into account constraints and at the same time make the agents work collectively avoiding the tragedy of commons to optimize the global/system objective. At the core of the PC optimization methodology are the concepts of Deterministic Annealing in Statistical Physics, Game Theory and Nash Equilibrium. Moreover, a rule‐based procedure is incorporated to handle solutions based on the number of constraints violated and drive the convergence towards feasibility. Two specially developed cases of the Circle Packing Problem with known solutions are solved and the true optimum results are obtained at reasonable computational costs. The proposed algorithm is shown to be sufficiently robust, and strengths and weaknesses of the methodology are also discussed.
Scanning Reduction Strategy in MEG/EEG Beamformer Source Imaging
Authors: Hong Jun Hee , Jun Sung Chan
Published: December 2011

MEG/EEG beamformer source imaging is a promising approach which can easily address spatiotemporal multi‐dipole problems without a priori information on the number of sources and is robust to noise. Despite such promise, beamformer generally has weakness which is degrading localization performance for correlated sources and is requiring of dense scanning for covering all possible interesting (entire) source areas. Wide source space scanning yields all interesting area images, and it results in lengthy computation time. Therefore, an efficient source space scanning strategy would be beneficial in achieving accelerated beamformer source imaging. We propose a new strategy in computing beamformer to reduce scanning points and still maintain effective accuracy (good spatial resolution). This new strategy uses the distribution of correlation values between measurements and lead‐field vectors. Scanning source points are chosen yielding higher RMS correlations than the predetermined correlation thresholds. We discuss how correlation thresholds depend on SNR and verify the feasibility and efficacy of our proposed strategy to improve the beamformer through numerical and empirical experiments. Our proposed strategy could in time accelerate the conventional beamformer up to over 40% without sacrificing spatial accuracy.
Th17 Response and Inflammatory Autoimmune Diseases
Authors: Waite Janelle C. , Skokos Dimitris
Published: December 2011

The proinflammatory activity of T helper 17 (Th17) cells can be beneficial to the host during infection. However, uncontrolled or inappropriate Th17 activation has been linked to several autoimmune and autoinflammatory pathologies. Indeed, preclinical and clinical data show that Th17 cells are associated with several autoimmune diseases such as arthritis, multiple sclerosis, psoriasis, and lupus. Furthermore, targeting the interleukin-17 (IL-17) pathway has attenuated disease severity in preclinical models of autoimmune diseases. Interestingly, a recent report brings to light a potential role for Th17 cells in the autoinflammatory disorder adult-onset Still's disease (AOSD). Whether Th17 cells are the cause or are directly involved in AOSD remains to be shown. In this paper, we discuss the biology of Th17 cells, their role in autoimmune disease development, and in AOSD in particular, as well as the growing interest of the pharmaceutical industry in their use as therapeutic targets.
Regulation of Monocarboxylate Transporter MCT1 Expression by p53 Mediates Inward and Outward Lactate Fluxes in Tumors
Authors: Boidot Romain , Végran Frédérique , Meulle Aline , Le Breton Aude , Dessy Chantal , Sonveaux Pierre , Lizard-Nacol Sarab , Feron Olivier
Published: December 2011

The monocarboxylate transporter (MCT) family member MCT1 can transport lactate into and out of tumor cells. Whereas most oxidative cancer cells import lactate through MCT1 to fuel mitochondrial respiration, the role of MCT1 in glycolysis-derived lactate efflux remains less clear. In this study, we identified a direct link between p53 function and MCT1 expression. Under hypoxic conditions, p53 loss promoted MCT1 expression and lactate export produced by elevated glycolytic flux, both in vitro and in vivo. p53 interacted directly with the MCT1 gene promoter and altered MCT1 mRNA stabilization. In hypoxic p53−/− tumor cells, NF-κB further supported expression of MCT1 to elevate its levels. Following glucose deprivation, upregulated MCT1 in p53−/− cells promoted lactate import and favored cell proliferation by fuelling mitochondrial respiration. We also found that MCT1 expression was increased in human breast tumors harboring p53 mutations and coincident features of hypoxia, with higher MCT1 levels associated with poorer clinical outcomes. Together, our findings identify MCT1 as a target for p53 repression and they suggest that MCT1 elevation in p53-deficient tumors allows them to adapt to metabolic needs by facilitating lactate export or import depending on the glucose availability. Cancer Res; 72(4); 939–48. ©2011 AACR.
Short-Term Outcomes of Laparoscopic Intersphincteric Resection for Lower Rectal Cancer and Comparison with Open Approach
Authors: Yamamoto Seiichiro , Fujita Shin , Akasu Takayuki , Inada Ryo , Takawa Masashi , Moriya Yoshihiro
Published: December 2011

Background/Aims: To evaluate the short-term surgical outcomes of laparoscopic intersphincteric resection (ISR) for lower rectal cancer, and to compare them with a case-control series of open ISR. Methods: Between July 2002 and March 2011, 29 patients with lower rectal cancer underwent laparoscopic ISR, and 22 of 29 patients who underwent laparoscopic ISR were compared with the control open ISR group of patients matched for age, gender, operative procedure and pathological stage. Results: There was no perioperative mortality, 8 complications occurred in 7 patients, and the morbidity rate was 24.1% (7/29). Leakage occurred in 1 patient (3.4%) in the laparoscopic ISR group. Regarding the matched case-control study, the operative time was significantly longer (p = 0.0007), but blood loss was significantly lower (p = 0.0003) in the laparoscopic ISR group. The median postoperative hospital stay was 8 days in the laparoscopic ISR group, which was significantly shorter than in the open ISR group (14 days). Postoperative complication rates were similar. In the laparoscopic ISR group, the levels of C-reactive protein on postoperative days 1–3 were significantly lower than in the open ISR group. Conclusions: Laparoscopic ISR for lower rectal cancer provides benefits in the early postoperative period without increasing morbidity or mortality.
Estimation and Visualization of Identity-by-Descent within Pedigrees Simplifies Interpretation of Complex Trait Analysis
Authors: Marchani Elizabeth E. , Wijsman Ellen M.
Published: December 2011

Linkage analysis identifies markers that appear to be co-inherited with a trait within pedigrees. The inheritance of a chromosomal segment may be probabilistically reconstructed, with missing data complicating inference. Inheritance patterns are further obscured in the analysis of complex traits, where variants in one or more genes may contribute to phenotypic variation within a pedigree. In this case, determining which relatives share a trait variant is not simple. We describe how to represent these patterns of inheritance for marker loci. We summarize how to sample patterns of inheritance consistent with genotypic and pedigree data using gl_auto, available in MORGAN v3.0. We describe identification of classes of equivalent inheritance patterns with the program IBDgraph. We finally provide an example of how these programs may be used to simplify interpretation of linkage analysis of complex traits in general pedigrees. We borrow information across loci in a parametric linkage analysis of a large pedigree. We explore the contribution of each equivalence class to a linkage signal, illustrate estimated patterns of identity-by-descent sharing, and identify a haplotype tagging the chromosomal segment driving the linkage signal. Haplotype carriers are more likely to share the linked trait variant, and can be prioritized for subsequent DNA sequencing.
Linkage Analysis in the Next-Generation Sequencing Era
Authors: Bailey-Wilson Joan E. , Wilson Alexander F.
Published: December 2011

Linkage analysis was developed to detect excess co-segregation of the putative alleles underlying a phenotype with the alleles at a marker locus in family data. Many different variations of this analysis and corresponding study design have been developed to detect this co-segregation. Linkage studies have been shown to have high power to detect loci that have alleles (or variants) with a large effect size, i.e. alleles that make large contributions to the risk of a disease or to the variation of a quantitative trait. However, alleles with a large effect size tend to be rare in the population. In contrast, association studies are designed to have high power to detect common alleles which tend to have a small effect size for most diseases or traits. Although genome-wide association studies have been successful in detecting many new loci with common alleles of small effect for many complex traits, these common variants often do not explain a large proportion of disease risk or variation of the trait. In the past, linkage studies were successful in detecting regions of the genome that were likely to harbor rare variants with large effect for many simple Mendelian diseases and for many complex traits. However, identifying the actual sequence variant(s) responsible for these linkage signals was challenging because of difficulties in sequencing the large regions implicated by each linkage peak. Current ‘next-generation’ DNA sequencing techniques have made it economically feasible to sequence all exons or the whole genomes of a reasonably large number of individuals. Studies have shown that rare variants are quite common in the general population, and it is now possible to combine these new DNA sequencing methods with linkage studies to identify rare causal variants with a large effect size. A brief review of linkage methods is presented here with examples of their relevance and usefulness for the interpretation of whole-exome and whole-genome sequence data.
The Sockeye Salmon Neo-Y Chromosome Is a Fusion between Linkage Groups Orthologous to the Coho Y Chromosome and the Long Arm of Rainbow Trout Chromosome 2
Authors: Faber-Hammond J. , Phillips R.B. , Park L.K.
Published: December 2011

Unlike other Pacific salmon, sockeye salmon (Oncorhynchus nerka) have an X1X2Y sex chromosome system, with females having a diploid chromosome number of 2n = 58 and males 2n = 57 in all populations examined. To determine the origin of the sockeye Y chromosome, we mapped microsatellite loci from the rainbow trout (O. mykiss; OMY) genetic map, including those found on the Y chromosomes of related species, in kokanee (i.e. non-anadromous sockeye) crosses. Results showed that 3 microsatellite loci from the long arm of rainbow trout chromosome 8 (OMY8q), linked to SEX (the sex-determining locus) in coho salmon (O. kisutch), are also closely linked to SEX in the kokanee crosses. We also found that 3 microsatellite loci from OMY2q are linked to those markers from OMY8q and SEX in kokanee, with both linkage groups fused to form the neo-Y. These results were confirmed by physical mapping of BAC clones containing microsatellite loci from OMY8q and OMY2q to kokanee chromosomes using fluorescence in situ hybridization. The fusion of OMY2q to the ancestral Y may have resolved sexual conflict and, in turn, may have played a large role in the divergence of sockeye from a shared ancestor with coho.
Loss-of-Function CNKSR2 Mutation Is a Likely Cause of Non-Syndromic X-Linked Intellectual Disability
Authors: Houge G. , Rasmussen I.H. , Hovland R.
Published: December 2011

In a non-dysmorphic 5-year-old boy with developmental delay, well-controlled epilepsy, and microcephaly, a 234-kb deletion of Xp22.12 was detected by copy number analysis. The maternally inherited deletion removed the initial 15 of the 21 exons of the connector enhancer of KSR-2 gene called CNKSR2 or CNK2. Our finding suggests that loss of CNKSR2 is a novel cause of non-syndromic X-linked mental retardation, an assumption supported by high gene expression in the brain, localization to the post-synaptic density, and a role in RAS/MAPK-dependent signal transduction.
Most Important Papers in ST-Elevation Myocardial Infarction
Authors:   The Editors
Published: December 2011

The following are highlights from the series,
Circulation: Cardiovascular Interventions
Topic Review. This series summarizes the most important manuscripts, as selected by the editors, that have published in the
Circulation
portfolio. The studies included in this article represent the most noteworthy research in the area of ST-elevation myocardial infarction. (
Circ Cardiovasc Interv.
2011;4:e55–e66.)
Impact of Blood Pressure and Blood Pressure Change During Middle Age on the Remaining Lifetime Risk for Cardiovascular Disease
Authors: Allen Norrina , Berry Jarett D. , Ning Hongyan , Van Horn Linda , Dyer Alan , Lloyd-Jones Donald M.
Published: December 2011

Background—

Prior estimates of lifetime risk (LTR) for cardiovascular disease (CVD) examined the impact of blood pressure (BP) at the index age and did not account for changes in BP over time. We examined how changes in BP during middle age affect LTR for CVD, coronary heart disease, and stroke.

Methods and Results—

Data from 7 diverse US cohort studies were pooled. Remaining LTRs for CVD, coronary heart disease, and stroke were estimated for white and black men and women with death free of CVD as a competing event. LTRs for CVD by BP strata and by changes in BP over an average of 14 years were estimated. Starting at 55 years of age, we followed up 61 585 men and women for 700 000 person-years. LTR for CVD was 52.5% (95% confidence interval, 51.3–53.7) for men and 39.9% (95% confidence interval, 38.7–41.0) for women. LTR for CVD was higher for blacks and increased with increasing BP at index age. Individuals who maintained or decreased their BP to normal levels had the lowest remaining LTR for CVD, 22% to 41%, compared with individuals who had or developed hypertension by 55 years of age, 42% to 69%, suggesting a dose-response effect for the length of time at high BP levels.

Conclusions—

Individuals who experience increases or decreases in BP in middle age have associated higher and lower remaining LTR for CVD. Prevention efforts should continue to emphasize the importance of lowering BP and avoiding or delaying the incidence of hypertension to reduce the LTR for CVD.