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Objectives: We sought to characterize UK-wide balloon aortic valvuloplasty (BAV) experience in the TAVI era. Background: BAV for acquired calcific aortic stenosis is in a phase of renaissance, largely due to the development of transcatheter aortic valve implantation (TAVI). Methods: Data from 423 patients at 14 centers across the UK were analyzed. Results: Patients were aged 80.9 6 9.5 years; 52.5% were male. Mean logistic EuroScore was 27.3% 6 16.8%. Mean peak transaortic gradient fell from 62.0 6 26.3 to 28.3 6 16.2 mm Hg. Aortic valve area increased from 0.58 6 0.19 to 0.80 6 0.25 cm 2 echocardiographically. Procedural complication rate was 6.3%, comprising death (2.4%), blood transfusion � 2 U (1.2%), cardiac tamponade (1.0%), stroke (1.0%), vascular surgical repair (1.0%), coronary embolism (0.5%), and permanent pacemaker (0.2%). Mortality was 13.8% at 30 days and 36.3% at 12 months. Subsequently, 18.3% of patients underwent TAVI and 7.0% sAVR, with improved survival compared to those who had no further intervention (logrank < 0.0001). Multivariate Cox proportional hazard analysis demonstrated that survival was adversely effected by the presence of coronary artery disease (HR 1.53, 95%CI 1.08‐2.17, P 5 0.018), poor LV function (HR 1.54, 95%CI 1.09‐2.16, P 5 0.014), and either urgent (HR 1.70, 95%CI 1.18‐2.45; P 5 0.004) or emergent presentation (HR 3.72, 95%CI 2.27‐6.08; P < 0.0001). Conclusion: Balloon aortic valvuloplasty offers good immediate hemodynamic efficacy at an acceptable risk of major complications. Medium-term prognosis is poor in the absence of definitive therapy. V C 2013 Wiley Periodicals, Inc.

Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease (CHD), with most cases occurring in patients with congenital cardiac shunts. In patients with an uncorrected left-to-right shunt, increased pulmonary pressure leads to vascular remodelling and dysfunction, resulting in a progressive rise in pulmonary vascular resistance and increased pressures in the right heart. Eventually, reversal of the shunt may arise, with the development of Eisenmenger's syndrome, the most advanced form of PAH-CHD. The prevalence of PAH-CHD has fallen in developed countries over recent years and the number of patients surviving into adulthood has increased markedly. Today, the majority of PAH- CHD patients seen in clinical practice are adults, and many of these individuals have complex disease or received a late diagnosis of their defect. While there have been advances in the management and therapy in recent years, PAH-CHD is a heterogeneous condition and some subgroups, such as those with Down's syndrome, present particular challenges. This article gives an overview of the demographics, pathophysiology and treatment of PAH- CHD and focuses on individuals with Down's syndrome as an important and challenging patient group.

Background Patients requiring congenital and structural heart interventions often require large-sized sheath insertion into femoral veins and arteries. Clinical outcome data on the use of suture-mediated devices for femoral venous access site closure are limited. Objective To assess the efficacy and safety of the Perclose™ (Abbott Vascular Devices, CA) suture-mediated device using the preclosure technique, in achieving haemostasis at femoral venous access site following large sheath insertion (≥8 Fr). Design and Setting Two hundred and forty-three consecutive patients underwent 310 access site closures with the Perclose™ device using the preclosure technique. There were 151 (62%) women, mean age 43 (±16) years. 234/243 (96%) received heparin. Mean venous access site sheath diameter was 11.5 (±3) Fr. Results Immediate haemostasis (

We have used a telemedicine facility to conduct academic teaching/training sessions. The objective of this study was to examine the feasibility, advantages, and disadvantages of this method of e-learning sessions. The teaching/learning sessions were organized twice a week between the two teaching hospitals. The success of each academic session was analyzed in terms of satisfaction of the participating candidates, infrastructure difficulties (if any), and the overall outcome of the program. In total, 293 academic sessions were held from 2008 to 2010. Each session's presentation was 45 min long and was made using Microsoft(®) (Redmond, WA) PowerPoint. We have found that telemedicine proved to be effective in establishing communication not only between the patient and the physician, but also between the teacher and the student. Several candidates benefited from the application of this technology. Candidates expressed satisfaction and were content with the teaching methods adapted.

Background Anomalies of the origin and course of the circumflex artery are amongst the most common seen at coronary angiography. There is limited information regarding patient and procedural characteristics, technical feasibility and outcomes associated with percutaneous intervention (PCI) to these vessels. The aim of this study is to examine our experience with PCI to anomalous circumflex vessels and compare this to some aspects of percutaneous intervention on non-anomalous circumflex vessels. Methods Over a 41month period, 20 PCI procedures on anomalous circumflex vessels were identified and 1550 PCI procedures on non-anomalous circumflex arteries. Results In 9 anomalous cases, the circumflex arose from the left coronary cusp, in 7 cases from the right coronary cusp, and in the remaining 4 cases from the proximal right coronary artery. There were no differences in demographics or pattern or severity of coronary disease between the 2 groups. A higher proportion of patients with anomalous vessels presented acutely. Screening times were longer in the anomalous group. All 20 procedures were associated with immediate procedural success. There was one peri-procedural myocardial infarction unrelated to anomalous circumflex intervention. After a median follow-up period of 7.3months, the only major adverse cardiac event recorded in the anomalous group was an ischaemia-driven revascularisation to a non-target vessel branch. We describe techniques which can be used to improve support and facilitate successful PCI to anomalous circumflex vessels. Conclusion PCI to anomalous circumflex vessels may be technically challenging, but is feasible and carries favourable short and long-term clinical outcomes. Summary This single centre observational study demonstrates that percutaneous coronary intervention to anomalous circumflex coronary arteries although technically challenging can be performed with satisfactory procedural success rates and favourable short and longer-term clinical outcomes. It describes various techniques that can be employed to optimise successful intervention.

SETTING Postgraduate (PG) residency programme of a tertiary care teaching hospital in southern India. OBJECTIVE To estimate the incidence of tuberculosis (TB) among PG residents, determine the frequency of exposure to infectious TB patients and assess whether particular specialties were associated with higher risk of exposure and incident TB. DESIGN We assembled an open cohort of PG residents who were on the academic rolls for more than 3 months at any time between December 2011 and January 2013. We collected data both retrospectively and prospectively using two surveys-an entry survey at study initiation or entry into the cohort, and an exit survey at residency completion or study closure. RESULTS Among 398 PG residents enrolled in the study, we identified five cases of incident TB during a cumulative follow-up period of 10 962 person-months. The incidence rate was 547 per 100 000 person-years, which was 3.1 times the incidence in the general population. Nearly two thirds (n = 257, 65%) of the residents were exposed to at least one infectious patient. Across the three specialty-based risk strata, there was an ordered increase in the median number of exposures (P < 0.001) and evaluation for presumptive TB (P = 0.024), as well as a trend towards higher incident TB. CONCLUSION TB incidence is significantly higher among PG residents than in the general population.

Functionalization of nanoparticles with cationic moieties, such as polyethyleneimine (PEI), enhances binding to the cell membrane; however, it also disrupts the integrity of the cell's plasma and vesicular membranes, leading to cell death. Primary fibroblasts were found to display high surface affinity for cationic iron oxide nanoparticles and greater sensitivity than their immortalized counterparts. Treatment of cells with cationic nanoparticles in the presence of incremental increases in serum led to a corresponding linear decrease in cell death. The surface potential of the nanoparticles also decreased linearly as serum increased and this was strongly and inversely correlated with cell death. While low doses of nanoparticles were rendered non-toxic in 25% serum, large doses overcame the toxic threshold. Serum did not reduce nanoparticle association with primary fibroblasts, indicating that the decrease in nanoparticle cytotoxicity was based on serum masking of the PEI surface, rather than decreased exposure. Primary endothelial cells were likewise more sensitive to the cytotoxic effects of cationic nanoparticles than their immortalized counterparts, and this held true for cellular responses to cationic microparticles despite the much lower toxicity of microparticles compared to nanoparticles.

The architecture of the mammalian brain has been characterized through decades of innovation in the field of network neuroscience. However, the assembly of the brain from progenitor cells is an immensely complex process, and a quantitative understanding of how neural progenitor cells (NPCs) form neural networks has proven elusive. Here, we introduce a method that integrates graph-theory with long-term imaging of differentiating human NPCs to characterize the evolution of spatial and functional network features in NPCs during the formation of neural networks in vitro. We find that the rise and fall in spatial network efficiency is a characteristic feature of the transition from immature NPC networks to mature neural networks. Furthermore, networks at intermediate stages of differentiation that display high spatial network efficiency also show high levels of network-wide spontaneous electrical activity. These results support the view that network-wide signaling in immature progenitor cells gives way to a hierarchical form of communication in mature neural networks. We also leverage graph theory to study the spatial features of individual cell types in developing cultures, uncovering spatial features of polarized neuroepithelium. Finally, we employ our method to uncover aberrant network features in a neurodevelopmental disorder using induced pluripotent stem cell (iPSC) models. The “Living Neural Networks” method bridges the gap between developmental neurobiology and network neuroscience, and offers insight into the relationship between developing and mature neural networks.

Myotonic dystrophy type 1(DM1) is the prototype for diseases caused by RNA toxicity. RNAs from the mutant allele contain an expanded (CUG)n tract within the 3' untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. The toxic RNAs affect the function of RNA binding proteins leading to sequestration of muscleblind-like (MBNL) proteins and increased levels of CELF1 (CUGBP, Elav-like family member 1). The mechanism for increased CELF1 is not very clear. One favored proposition is hyper-phosphorylation of CELF1 by Protein Kinase C alpha (PKCα) leading to increased CELF1 stability. However, most of the evidence supporting a role for PKC-α relies on pharmacological inhibition of PKC. To further investigate the role of PKCs in the pathogenesis of RNA toxicity, we generated transgenic mice with RNA toxicity that lacked both the PKCα and PKCβ isoforms. We find that these mice show similar disease progression as mice wildtype for the PKC isoforms. Additionally, the expression of CELF1 is also not affected by deficiency of PKCα and PKCβ in these RNA toxicity mice. These data suggest that disease phenotypes of these RNA toxicity mice are independent of PKCα and PKCβ.

This study sought to evaluate the outcomes of the early experience of transcatheter mitral valve replacement (TMVR) with balloon-expandable valves in patients with severe mitral annular calcification (MAC) and reports the first large series from a multicenter global registry.The risk of surgical mitral valve replacement in patients with severe MAC is high. There are isolated reports of successful TMVR with balloon-expandable valves in this patient population.We performed a multicenter retrospective review of clinical outcomes of patients with severe MAC undergoing TMVR.From September 2012 to July of 2015, 64 patients in 32 centers underwent TMVR with compassionate use of balloon-expandable valves. Mean age was 73 ± 13 years, 66% were female, and mean Society of Thoracic Surgeons score was 14.4 ± 9.5%. The mean mitral gradient was 11.45 ± 4.4 mm Hg and the mean mitral area was 1.18 ± 0.5 cm(2). SAPIEN valves (Edwards Lifesciences, Irvine, California) were used in 7.8%, SAPIEN XT in 59.4%, SAPIEN 3 in 28.1%, and Inovare (Braile Biomedica, Brazil) in 4.7%. Access was transatrial in 15.6%, transapical in 43.8%, and transseptal in 40.6%. Technical success according to Mitral Valve Academic Research Consortium criteria was achieved in 46 (72%) patients, primarily limited by the need for a second valve in 11 (17.2%). Six (9.3%) had left ventricular tract obstruction with hemodynamic compromise. Mean mitral gradient post-procedure was 4 ± 2.2 mm Hg, paravalvular regurgitation was mild or absent in all. Thirty-day all-cause mortality was 29.7% (cardiovascular = 12.5% and noncardiac = 17.2%); 84% of the survivors with follow-up data available were in New York Heart Association functional class I or II at 30 days (n = 25).TMVR with balloon-expandable valves in patients with severe MAC is feasible but may be associated with significant adverse events. This strategy might be an alternative for selected high-risk patients with limited treatment options.

The cellular proteolytic machinery orchestrates protein turnover and regulates several key biological processes. This study addresses the roles of Lon, a major ATP-dependent protease, in modulating the responses of Escherichia coli strain MG1655 to low and high amounts of sodium salicyclate (NaSal), a widely used clinically relevant analgesic. NaSal affects several bacterial responses, including growth and resistance to multiple antibiotics. The loss of lon reduces growth in response to high, but not low, amounts of NaSal. From amongst a panel of Lon substrates, MarA was identified to be the downstream target of Lon. Thus, stabilization of MarA in the absence of lon lowers growth of the strain in the presence of higher amounts of NaSal. The steady-state transcript levels of marA and its target genes, acrA, acrB and tolC, are higher in the Δlon strain compared with the WT strain. Consequently, the resistance to antibiotics, e.g. tetracycline and nalidixic acid, is enhanced in Δlon in a marA-dependent manner. Furthermore, the target genes of MarA, i.e. acrB and tolC, are responsible for NaSal-mediated antibiotic resistance. Studies using atomic force microscopy demonstrated that ciprofloxacin led to greater cell filamentation, which is lower in the Δlon strain due to higher levels of MarA. Overall, this study delineates the roles of Lon protease, its substrate MarA and downstream targets of MarA, e.g. acrB and tolC, during NaSal-mediated growth reduction and antibiotic resistance. The implications of these observations in the adaptation of E. coli under different environmental conditions are discussed.

The most common reason for reintervention after a Björk modification of the Fontan procedure, in which the right ventricle (RV) is incorporated into the pulmonary circulation by connecting the right atrial (RA) appendage to the RV directly or with an extra-anatomic graft, is obstruction or regurgitation of the RA-RV connection. Transcatheter implantation of a valved stent is an appealing option for the treatment of RA-RV conduit dysfunction in these patients. In the present study, we assessed early and intermediate results after transcatheter valve implantation within an obstructed or regurgitant RA-RV modified Fontan pathway.Through a retrospective multicenter registry, we collected data from 16 patients with a modified Fontan circulation who were treated with percutaneous Melody or Sapien valve implantation for dysfunction of an extra-anatomic RA-RV conduit or valve.All patients had successful and uncomplicated implantation of a Melody (n = 15) or Sapien 3 (n = 1) valve with hemodynamic and, in most cases, clinical improvement. During a median follow-up of 3.3 years, 3 patients died of cardiovascular causes unrelated to the procedure or the valve, and no major valve dysfunction was observed.Percutaneous transcatheter valve deployment to treat a dysfunctional RA-RV connection after a Björk modification of the Fontan procedure is a viable alternative to surgery, with low procedural risk, and appears to offer good early and intermediate results.© 2016 Wiley Periodicals, Inc.

Background: Patients with pulmonary arterial\ud hypertension (PAH) are managed according to\ud evidence-based treatment guidelines.\ud Methods and results: In this single-centre\ud retrospective analysis, we examined outcomes of\ud patients with PAH caused by congenital heart disease\ud (PAH-CHD) with respect to exercise capacity and\ud survival of adults treated with either bosentan or\ud sildenafil monotherapy or bosentan-sildenafil dual\ud therapy between January 2007 and January 2014. Of\ud the 82 patients analysed, 29 had Down syndrome; 54\ud (65.8%) received bosentan monotherapy, 16 (19.5%)\ud sildenafil monotherapy and 12 (14.6%) dual therapy.\ud Mean treatment duration was 2.5 years for all patients\ud and 4.1 years for 38 patients treated for ≥2 years.\ud Pooled patient and treatment data showed initial\ud improvement followed by stabilisation in mean 6 min\ud walk distance (6MWD). For Down and non-Down\ud patients, mean 6MWD increased and then stabilised on\ud bosentan monotherapy. Mean 6MWD of patients on\ud dual therapy at the time of analysis was 246.3 m\ud before PAH-specific therapy initiation, 211.9 m\ud immediately prior to addition of a second therapy and\ud 214.4 m at last visit while on dual therapy. 1, 2 and 3-\ud year survival rates for all patients from time of\ud treatment initiation were 96%, 87% and 80%,\ud respectively.\ud Conclusions: For the majority of patients,\ud monotherapy with a PAH-specific medication provided\ud improved and sustained exercise benefits. For the small\ud percentage of patients who required it, add-on therapy\ud appeared to prevent further deterioration in exercise\ud capacity but did not improve 6MWD.

© 2016, BMJ Publishing Group. All rights reserved. Background: The presence of mitral valve prolapse (MVP) in congenital heart disease (CHD) patients is not well described. Tetralogy of Fallot (TOF) is the most common cyanotic CHD associated with overall good long-term survival after palliation. Since MVP is more often identified in adults and TOF patients are now surviving longer, we thus sought to perform this cohort study with a case-control design to (1) determine the prevalence of MVP and systolic displacement of mitral leaflets (SDML) in adult TOF patients, and (2) describe their clinical and imaging characteristics. Methods: Retrospective interrogation of our echocardiography database identified 328 consecutive TOF patients ≥18 years from 1 January 2000 to 31 December 2014. All images were reviewed to identify patients with concomitant MVP (prolapse >2 mm beyond the long-axis annular plane) or SDML (

We use the Fourier transform based Warren–Averbach (WA) analysis to separate the contributions of X-ray diffraction (XRD) profile broadening due to crystallite size and microstrain for magnetic iron oxide nanoparticles. The profile shape of the column length distribution, obtained from WA analysis, is used to analyze the shape of the magnetic iron oxide nanoparticles. From the column length distribution, the crystallite size and its distribution are estimated for these nanoparticles which are compared with size distribution obtained from dynamic light scattering measurements. The crystallite size and size distribution of crystallites obtained from WA analysis are explained based on the experimental parameters employed in preparation of these magnetic iron oxide nanoparticles. The variation of volume weighted diameter ( D v , from WA analysis) with saturation magnetization ( M s ) fits well to a core shell model wherein it is known that M s = M bulk (1−6 g / D v ) with M bulk as bulk magnetization of iron oxide and g as magnetic shell disorder thickness.

A domain decomposed Monte Carlo communication kernel is used to carry out performance tests to establish the feasibility of using Monte Carlo techniques for practical Light Water Reactor (LWR) core analyses. The results of the prototype code are interpreted in the context of simplified performance models which elucidate key scaling regimes of the parallel algorithm.

The modeling of nuclear reactors involves the solution of a multiphysics problem with various time and length scales. Mathematically, this requires solving a system of coupled, nonlinear, stiff, Partial Differential Equations (PDEs). This paper deals with the verification aspects associated with a multiphysics code, i.e., the substantiation that the mathematical description of the multiphysics equations are solved correctly (in time and space). Multiphysics applications have the added complexity that the solution field participates in various physics components, potentially yielding spatial and/or temporal coupling errors. We present a multiphysics framework that tightly couples the various physical models using the Jacobian-free Newton-Krylov technique (JFNK) and show that high-order convergence can be achieved in both space and time. Code verification results are provided.

Staufen1 interacts with mRNAs with expanded CUG repeats and promotes their nuclear export and translation, while also promoting alternative splicing of other mRNAs., In myotonic dystrophy type 1 (DM1), dystrophia myotonica protein kinase messenger ribonucleic acids (RNAs; mRNAs) with expanded CUG repeats (CUGexp) aggregate in the nucleus and become toxic to cells by sequestering and/or misregulating RNA-binding proteins, resulting in aberrant alternative splicing. In this paper, we find that the RNA-binding protein Staufen1 is markedly and specifically increased in skeletal muscle from DM1 mouse models and patients. We show that Staufen1 interacts with mutant CUGexp mRNAs and promotes their nuclear export and translation. This effect is critically dependent on the third double-stranded RNA–binding domain of Staufen1 and shuttling of Staufen1 into the nucleus via its nuclear localization signal. Moreover, we uncover a new role of Staufen1 in splicing regulation. Overexpression of Staufen1 rescues alternative splicing of two key pre-mRNAs known to be aberrantly spliced in DM1, suggesting its increased expression represents an adaptive response to the pathology. Altogether, our results unravel a novel function for Staufen1 in splicing regulation and indicate that it may positively modulate the complex DM1 phenotype, thereby revealing its potential as a therapeutic target.

This report describes to employ SHARP to perform a first-of-a-kind analysis of the core radial expansion phenomenon in an SFR. This effort required significant advances in the framework Multi-Physics Demonstration Problem with the SHARP Reactor Simulation Toolkit used to drive the coupled simulations, manipulate the mesh in response to the deformation of the geometry, and generate the necessary modified mesh files. Furthermore, the model geometry is fairly complex, and consistent mesh generation for the three physics modules required significant effort. Fully-integrated simulations of a 7-assembly mini-core test problem have been performed, and the results are presented here. Physics models of a full-core model of the Advanced Burner Test Reactor have also been developed for each of the three physics modules. Standalone results of each of the three physics modules for the ABTR are presented here, which provides a demonstration of the feasibility of the fully-integrated simulation.

Shattered rim cracking, propagation of a subsurface crack parallel to the tread surface, is one of the dominant railroad wheel failure types observed in North America. This crack initiation and propagation life depends on several factors, such as wheel rim thickness, wheel load, residual stresses in the rim, and the size and location of material defects in the rim. This article investigates the effect of the above-mentioned parameters on shattered rim cracking, using finite element analysis and fracture mechanics. This cracking is modelled using a three-dimensional, multiresolution, elastic–plastic finite element model of a railroad wheel. Material defects are modelled as mathematically sharp cracks. Rolling contact loading is simulated by applying the wheel load on the tread surface over a Hertzian contact area. The equivalent stress intensity factor ranges at the subsurface crack tips are estimated using uni-modal stress intensity factors obtained from the finite element analysis and a mixed-mode crack growth model. The residual stress and wheel wear effects are also included in modelling shattered rim cracking. The analysis results show that the sensitive depth below the tread surface for shattered rim cracking ranges from 19.05 to 22.23 mm, which is in good agreement with field observations. The relationship of the equivalent stress intensity factor (Δ K eq) at the crack tip to the load magnitude is observed to be approximately linear. The analysis results show that the equivalent stress intensity factor (Δ K eq) at the crack tip depends significantly on the residual stress state in the wheel. Consideration of as-manufactured residual stresses decreases the Δ K eq at the crack tip by about 40 per cent compared to that of no residual stress state, whereas consideration of service-induced residual stresses increases the Δ K eq at the crack tip by about 50 per cent compared to that of as-manufactured residual stress state. In summary, the methodology developed in this article can help to predict whether a shattered rim crack will propagate for a given set of parameters, such as load magnitude, rim thickness, crack size, crack location, and residual stress state.

Myotonic dystrophy (DM1), the most common adult muscular dystrophy, is a multisystem, autosomal dominant genetic disorder caused by an expanded CTG repeat that leads to nuclear retention of a mutant RNA and subsequent RNA toxicity. Significant insights into the molecular mechanisms of RNA toxicity have led to the previously unforeseen possibility that treating DM1 is a viable prospect. In this review, we briefly present the clinical picture in DM1, and describe how the research in understanding the pathogenesis of RNA toxicity in DM1 has led to targeted approaches to therapeutic development at various steps in the pathogenesis of the disease. We discuss the promise and current limitations of each with an emphasis on RNA-based therapeutics and small molecules. We conclude with a discussion of the unmet need for clinical tools and outcome measures that are essential prerequisites to proceed in evaluating these potential therapies in clinical trials.

A new approach based on nonlinear ultrasonic (NLU) technique is presented for nondestructive evaluation of yield strength and tensile strength of cold worked AISI type 304 stainless steel (SS). In this approach, the ultrasonic harmonics generated in cold worked stainless steel, as a result of interaction of ultrasonic wave with dislocations and substructural changes, are measured precisely and the nonlinear ultrasonic parameter, β is determined. A quadratic relationship, with a correlation coefficient better than 0.99, is found between the yield strength and the β parameter as well as between the tensile strength and β parameter of the cold worked specimens. The observed behavior is explained based on microscopy, variations in martensite volume fraction and dislocation density determined from X-ray diffraction profile analysis. The proposed approach can be effectively used for nondestructively ensuring the uniformity of tensile properties of steel components on shop-floor during various stages of manufacturing and also as feedback module in intelligent processing of materials concept.

The pressure wire has emerged as a useful tool to assess the clinical severity of moderate coronary artery lesions. We report a novel use of the pressure wire in adult patients with complex congenital cardiac disease in whom it was used in assessing pressures beyond the stenosis in the distal pulmonary artery, aorto-pulmonary collaterals, and across prosthetic tricuspid valves, where conventional catheters were unable to reach. We used this in three of our patients for assessment of pulmonary artery pressures and in two patients for assessment of pressures across a prosthetic St Jude® valve. Out of the three patients referred for assessment, only two had significantly raised distal pulmonary pressures enabling them to receive appropriate therapy. Out of the two patients with a prosthetic tricuspid valve, only one required surgery based on this assessment. We describe a novel use of the pressure wire in the functional assessment of adults with congenital cardiac disease in whom conventional catheter techniques may not be able to provide adequate data. It can be a guide to provide appropriate therapy and avoid unnecessary interventions in this patient group.

The Q-values and half-lives of several heavy α decaying systems are calculated using the relativistic mean field (RMF) theory-based microscopic α-daughter nucleus potential. A unified procedure is adopted, using analytic S-matrix method and treating α-decay as the decay of the resonance state of the α-daughter nucleus system. The resonance parameters are obtained from the pole positions of the S-matrix in the complex k-plane and using these Q-values and half widths are evaluated. The calculation reproduces the experimental results well. We find that the present unified approach gives a good description of the data and compare well with those obtained by empirical formulae.

Nonlinear ultrasonic (NLU) technique is used for characterization of microstructures in M250 grade maraging steel subjected to solution annealing at 1093 K for 1 h followed by ageing at 755 K for various ageing durations in the range from 0.25 to 100 h. Using pulse inversion technique, feeble second harmonic is extracted to determine nonlinear ultrasonic parameter, β, and the relative β parameter (RBP) which is the ratio of β parameter of the precipitation hardened specimen to that of the solution annealed specimen. Normalized mean square strain, volume fraction of reverted austenite and hardness have been measured and transmission electron microscopy (TEM) has been carried out to understand the microstructural changes that occur during ageing and to study the correlation between these measured parameters. Hardness and normalized mean square strain are found to increase during initial stages of ageing due to precipitation of intermetallics and decrease at longer durations due to formation of reverted austenite and coarsening of precipitates. This study establishes that NLU technique can be used for non-destructive characterization of ageing behaviour of M250 grade maraging steel.

OBJECTIVES: To assess procedural and clinical outcomes in adults with severe aortic stenosis (AS) undergoing percutaneous aortic balloon valvuloplasty (PABV), who are considered unsuitable on initial assessment for surgical aortic valve replacement or transcatheter aortic valve implantation (TAVI). BACKGROUND: Surgical valve replacement provides better outcomes than conservative treatment for patients with severe symptomatic AS; however, patients with multiple comorbidities or hemodynamic instability carry a high operative risk. While TAVI offers an alternative to surgery, not all patients are suitable. This study looks at medium-term outcomes in a series of high-risk patients undergoing PABV. METHODS: Pre- and postprocedure aortic valve gradients were measured by catheterization and echocardiography. Patients were assessed for symptomatic benefit and clinical outcomes. RESULTS: Over 4 years, 42 patients underwent PABV. Mean clinical follow-up was 8 +/- 5.8 months and survival was 63%. Mean echocardiographic aortic valve gradient fell from 84.6 +/- 27 mmHg to 51.3 +/- 16 mmHg (p < 0.05). In 29% (12/42) patients, PABV was performed as a bridge to definitive AVR. Four had surgical AVR and six had TAVI. Two had successful noncardiac surgery. Four patients died in the periprocedural period and all were in cardiogenic shock. Patients were in New York Heart Association (NYHA) class IV decreased from 60% to 5% postprocedure (p < 0.05). CONCLUSION: PABV is useful as a palliation or bridge to definitive therapy for treatment of patients with severe AS unsuitable for surgery. It is associated with good medium-term cardiac outcomes and enables some patients to receive definitive therapy.

Ebstein anomaly is a congenital malformation of the tricuspid valve (TV) with right ventricular(RV) myopathy. There is wide range of presentation from patients who are asymptomatic to various degree of RV failure. We present a 32 year old male who presents with palpitations and shortness of breath

Cobalt ferrite nanoparticles of different sizes are prepared by varying the concentration of Co2+ metal ions using precipitation approach. The average crystallite size, coercivity (HC), and saturation magnetization (MS) increases from 11 to 16 nm, 0.12 to 0.8 kOe, and 28 to 52 emu/g, respectively, as Co2+ ion concentration is reduced from 0.4 to 0.025 M. High resolution transmission electron microscopy and X-ray diffraction analysis confirms that CoFe2O4 nanoparticles are crystalline in nature with cubic structure. Raman spectroscopic investigation shows traces of paramagnetic ferrihydrite in samples prepared with Co2+ ion concentration greater than 0.1 M. These experimental results suggest that metal ion concentration plays an important role in the size, magnetic property and purity of precipitated cobalt ferrite nanoparticles. The variation in the average crystalline size with Co2+ ion concentration is in good agreement with the nucleation theory. Our approach is useful in tuning the size and magnetic p...

In analogy with the definition of resonant or quasi-bound states used in three-dimensional quantal scattering, we define the quasi-bound states that occur in one-dimensional transmission generated by twin symmetric potential barriers and evaluate their energies and widths using two typical examples: (i) twin rectangular barrier and (ii) twin Gaussian-type barrier. The energies at which reflectionless transmission occurs correspond to these states and the widths of the transmission peaks are also the same as those of quasi-bound states. We compare the behaviour of the magnitude of wave functions of quasi-bound states with those for bound states and with the above-barrier state wave function. We deduce a Breit-Wigner-type resonance formula which neatly describes the variation of transmission coefficient as a function of energy at below-barrier energies. Similar formula with additional empirical term explains approximately the peaks of transmission coefficients at above-barrier energies as well. Further, we study the variation of tunnelling time as a function of energy and compare the same with transmission, reflection time and Breit-Wigner delay time around a quasi-bound state energy. We also find that tunnelling time is of the same order of magnitude as lifetime of the quasi-bound state, but somewhat larger.

Assessment of fatigue damage during the service life of any component is important to ensure its continued integrity and predict the remnant life of the component. This is important to reduce the overall life cycle cost of the components. A component undergoing fluctuating stresses experiences fatigue damage and this is one of the major causes of failure of engineering components. Accumulation of fatigue damage takes place in undercarriages of aircrafts due to fluctuating stresses experienced after each landing. The accumulated fatigue damage has been assessed by carrying out residual stress measurements at stress critical regions of the undercarriages using X-ray diffraction technique. In the undercarriages, high compressive residual stresses are introduced as part of fabrication process, to enhance the fatigue resistance. These compressive residual stresses get redistributed due to the localized plastic deformation and become tensile with the increase in number of landings. The life of the undercarriages is extended by employing a rejuvenation treatment to overcome the surface tensile residual stresses, by first removing the material from stress critical regions, followed by shot peening treatment which introduces surface compressive stresses, thus enabling continued use of the undercarriages. The additional thickness provided at the design stage enables removal of fatigue damaged surface layers without affecting the overall structural integrity. The residual stress redistribution in stress critical regions of the struts of the undercarriages was measured and found to match qualitatively well with the values predicted from FEM based simulations.

Three-dimensional finite element (FE) modeling of remote field eddy current (RFEC) technique has been performed to detect localized defects in ferromagnetic steam generator tubes. The excitation frequency, intercoil spacing, and the design of localized receiver coil have been optimized using this model. Amplitude and phase of RFEC signals of radial and axial receiver coils have been predicted for a through hole and two flat bottom holes (FBH). The detection sensitivity of the receiver coils has been compared, and the model has been validated for a few cases.

Conventional coupling paradigms currently used to couple different physics components in reactor analysis problems can be inconsistent in their treatment of the nonlinear terms due to the operator-split (OS) strategies employed. This leads to the usage of small time steps to maintain accuracy requirements, thereby increasing the overall computational time. This paper proposes some remedies to OS techniques that can restore consistency in the coupling of the nonlinear terms and explores high-order mono-block nonlinearly consistent techniques with time step control. The performance of the methods was studied for several transient scenarios using a 0D point-kinetics/thermal-hydraulics lumped model and a 1D neutronics/heat conduction/enthalpy balance model. The results prove that consistent approximations can be made to enhance the overall accuracy in conventional codes with simple nonintrusive techniques. Additionally, an analysis of a mono-block coupling strategy (without having recourse to an OS strategy) is carried out to assess automated time stepping control using higher order Implicit Runge–Kutta (IRK) schemes. The conclusions from these results indicate that nonlinearly consistent adaptive time stepping methods can provide better accuracy and reliability in the solution fields than constant time stepping methods, even for transients with rapid and discontinuous variations.

In myotonic dystrophy type I (DM1), nuclear retention of mutant DMPK transcripts compromises muscle cell differentiation. Although several reports have identified molecular defects in myogenesis, it remains still unclear how exactly the retention of the mutant transcripts induces this defect. We have recently created a novel cellular model in which the mutant DMPK 3' UTR transcripts were released to the cytoplasm of myoblasts by using the WPRE genetic element. As a result, muscle cell differentiation was repaired. In this paper, this cellular model was further exploited to investigate the effect of the levels and location of the mutant transcripts on muscle differentiation. Results show that the levels of these transcripts were proportional to the inhibition of both the initial fusion of myoblasts and the maturity of myotubes. Moreover, the cytoplasmic export of the mutant RNAs to the cytoplasm caused less inhibition only in the initial fusion of myoblasts.

Determination of lattice misfit and microstructural parameters of the coherent precipitates in Ni based alloy Inconel-625 is a challenging problem as the diffraction peaks of the precipitate and the matrix are completely overlapping. X-ray Diffraction Line Profile Analysis (XRDLPA) has been used to characterize the bulk samples of Inconel 625 at different heat-treated conditions to determine the lattice parameters of the parent phase and also the coherent precipitates by the separation of the overlapping peaks. The lattice misfits of the coherent precipitates with the matrix and their microstructural parameters like size and strain have also been determined.

X-ray diffraction (XRD) studies were carried out to characterize aging behavior of M250 grade maraging steel samples subjected to isothermal aging at 755 K for varying durations of 0.25, 1, 3, 10, 40, 70, and 100 hours. Earlier studies had shown typical features of precipitation hardening, wherein the hardness increased to a peak value due to precipitation of intermetallics and decreased upon further aging (overaging) due to reversion of martensite to austenite. Intermetallic precipitates, while coherent, are expected to increase the microstrain in the matrix. Hence, an attempt has been made in the present study to understand the microstructural changes in these samples using XRD line profile analysis. The anisotropic broadening with diffraction angle observed in the simple Williamson-Hall (WH) plot has been addressed using the modified WH (mWH) approach, which takes into account the contrast caused by dislocations on line profiles, leading to new scaling factors in the WH plot. The normalized mean square strain and crystallite size estimated from mWH have been used to infer early precipitation and to characterize aging behavior. The normalized mean square strain has been used to determine the Avrami exponent in the Johnson-Mehl-Avrami (JMA) equation, which deals with the kinetics of precipitation. The Avrami exponent thus determined has matched well with values found by other methods, as reported in literature.

A comparative study of the S-matrix and the WKB methods for the calculation of the half widths of alpha decay of super heavy elements is presented. The extent of the reliability of the WKB methods is demonstrated through simple illustrative examples. Detailed calculations have been carried out using the microscopic alpha-daughter potentials generated in the framework of the double-folding model using densities obtained in the relativistic mean field theories. We consider alpha-nucleus systems appearing in the decay chains of super heavy parent elements having A = 277, Z = 112 and A = 269, Z = 110. For negative and small positive log τ1/2 values the results from both methods are similar even though the S-matrix results should be considered to be more accurate. However, when log τ1/2 values are large and positive, the width associated with such state is infinitesimally small and hence calculation of such width by the S-matrix pole search method becomes a numerically difficult problem. We find that overall, the WKB method is reliable for the calculation of half lives of alpha decay from heavy nuclei.

Myotonic muscular dystrophy (DM1) is the most common inherited neuromuscular disorder in adults and is considered the first example of a disease caused by RNA toxicity. Using a reversible transgenic mouse model of RNA toxicity in DM1, we provide evidence that DM1 is associated with induced NKX2-5 expression. Transgene expression resulted in cardiac conduction defects, increased expression of the cardiac-specific transcription factor NKX2-5 and profound disturbances in connexin 40 and connexin 43. Notably, overexpression of the DMPK 3' UTR mRNA in mouse skeletal muscle also induced transcriptional activation of Nkx2-5 and its targets. In human muscles, these changes were specific to DM1 and were not present in other muscular dystrophies. The effects on NKX2-5 and its downstream targets were reversed by silencing toxic RNA expression. Furthermore, using Nkx2-5+/- mice, we show that NKX2-5 is the first genetic modifier of DM1-associated RNA toxicity in the heart.

To investigate the effect of endovascular stenting of aortic coarctation on biventricular function in adults during intermediate-term follow-up.21 patients (age 34 (10) years) were studied prospectively before and 14 (2) months after coarctation stenting from year 2002 to 2005. Biventricular function and blood pressure measurements were made. The post-stenting results were compared with pre-stenting values (group 1), with 22 age- and sex-matched post-surgical repair patients (group 2) and 30 normal controls (group 3).The peak systolic gradient across the coarctation site fell (55 (15) mm Hg to 18 (8) mm Hg, p0.001). Systolic, mean blood pressure and left ventricular (LV) mass dropped after stenting (p0.05 for all). LV long-axis function improved at intermediate-term follow-up (tissue Doppler imaging lateral and septal systolic and diastolic velocities and E/Em ratios: LSm, 6.5 (1.4) cm/s to 7.9 (1.7) cm/s; SSm, 5.8 (1.2) cm/s to 7.3 (1.6) cm/s; LEm, 8.1 (1.3) to 9.4 (2.3) cm/s; SEm, 6.7 (1.5) cm/s to 7.8 (1.9) cm/s; LE/Em, 11.2 (2.7) to 9.8 (2.8); SE/Em, 14.8 (5.3) to 11.8 (3.9); p0.05 for all). No significant difference in LV ejection fraction, conventional LV diastolic measurements (E, A, E/A ratio, IVRT and DT) was found after stenting. No significant deterioration of right ventricular function was seen in stented patients. Both post-stenting and post-surgical repair patients had poorer LV long-axis function than controls (p0.01 for all).Endovascular stenting of aortic coarctation resulted in medium-term LV mass regression and long-axis function improvement that may provide insight into long-term outcome of the stented patients. The results support aortic stenting in patients with anatomically suitable defects, given the additional benefit of avoiding cardiopulmonary bypass. The clinical significance of subclinical myocardial dysfunction in patients with stented or repaired coarctation warrants further studies.

In February 1944, when the whole world was consumed by the ravages of a World War, an important paper appeared in the rather obscure Journal of Experimental Medicine, entitled “Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Deoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III”. The principal author of the paper was a short, soft-spoken physician of Canadian origin, Oswald Theodore Avery. The carefully reasoned paper of Avery and his colleagues at the Rockefeller Institute in New York, Colin MacLeod and Maclyn McCarty, was the culmination of meticulous work carried out for over a decade, following the startling results on pneumococcal transformation reported by the British physician Frederick Griffith in 1928. Though the paper was initially met with scepticism from the scientific community, it went on to pave the way for ushering in the new field of molecular genetics. It was also the inspiration for a young American graduate student by the name of James Watson, to team up with the British biophysicist Francis Crick, to solve the structure of DNA. This article attempts to highlight the triumphs and disappointments in the pursuit of the identification of the “transforming principle”.

Nanoparticles synthesized using co-precipitation technique from iron salt solutions at different pH and temperatures are found to consist of magnetite, magnetite-goethite mixtures and goethite particles depending on process conditions. The synthesized particles are characterized using X-ray diffraction (XRD) technique and their magnetic properties are evaluated using a vibrating sample magnetometer (VSM). As properties of these nanoparticles are essentially dependent on various phases present, a detailed phase analysis and quantification of the magnetite phase in magnetite-goethite mixed system has been carried out using XRD technique. For quantification, a calibration graph has been made using samples of magnetite and goethite mixed in different weight percentages. Using this calibration graph, magnetite weight percentages have been estimated in mixed particles produced by co-precipitation from iron salt solutions at various pH values. A good correlation between saturation magnetization values and magnetite weight percentage has been observed in these mixed particles. When the synthesized particles are pure magnetite, the saturation magnetization value is found to depend on the diameter of the particles, estimated using XRD and VSM data.

The prospect of graft loss is a problem faced by all transplant recipients, and retransplantation is often an option when loss occurs. To assess current trends in retransplantation, we analyzed data for retransplant candidates and recipients over the last 10 years, as well as current outcomes. During 2005, retransplant candidates represented 13.5%, 7.9%, 4.1% and 5.5% of all newly registered kidney, liver, heart and lung candidates, respectively. At the end of 2005, candidates for retransplantation accounted for 15.3% of kidney transplant candidates, and lower proportions of liver (5.1%), heart (5.3%) and lung (3.3%) candidates. Retransplants represented 12.4% of kidney, 9.0% of liver, 4.7% of heart and 5.3% of lung transplants performed in 2005. The absolute number of retransplants has grown most notably in kidney transplantation, increasing 40% over the last 10 years; the relative growth of retransplantation was most marked in heart and lung transplantation, increasing 66% and 217%, respectively. The growth of liver retransplantation was only 11%. Unadjusted graft survival remains significantly lower after retransplantation in the most recent cohorts analyzed. Even with careful case mix adjustments, the risk of graft failure following retransplantation is significantly higher than that observed for primary transplants.

We report the effect of initial pH and temperature of iron salt solutions on formation of magnetite (Fe3O4) nanoparticles during co-precipitation. We synthesized nanoparticles by keeping the initial pH at 0.7, 1.5, 3.0, 4.7, 5.7, 6.7 for two different temperatures of 30 and 60 ◦ C. When the initial pH (prior to alkali addition) of the salt solution was below 5, the nanoparticles formed were 100% spinel iron oxide. Average size of the magnetite particles increases with initial pH until ferrihydrite is formed at a pH of 3 and the size remains the same till 4.7 pH. The percentage of goethite formed along with non-stoichiometric magnetite was 35 and 78%, respectively, when the initial pH of the solution was 5.7 and 6.7. As the reaction temperature was increased to 60 ◦ C, maintaining a pH of 6.7, the amount of goethite increased from 78 to 100%. These results show that the initial pH and temperature of the ferrous and ferric salt solution before initiation of the precipitation reaction are critical parameters controlling the composition and size of nanoparticles formed. We characterize the samples using X-ray diffraction, transmission electron microscopy and vibrating sample magnetometer. The results of the present work provide the right conditions to synthesis pure magnetite nanoparticles, without goethite impurities, through co-precipitation technique for ferrofluid applications. © 2007 Elsevier B.V. All rights reserved.