Distinct retroelement classes define evolutionary breakpoints demarcating sites of evolutionary novelty

<p>Abstract</p> <p>Background</p> <p>Large-scale genome rearrangements brought about by chromosome breaks underlie numerous inherited diseases, initiate or promote many cancers and are also associated with karyotype diversification during species evolution. Recent research has shown that these breakpoints are nonrandomly distributed throughout the mammalian genome and many, termed "evolutionary breakpoints" (EB), are specific genomic locations that are "reused" during karyotypic evolution. When the phylogenetic trajectory of orthologous chromosome segments is considered, many of these EB are coincident with ancient centromere activity as well as new centromere formation. While EB have been characterized as repeat-rich regions, it has not been determined whether specific sequences have been retained during evolution that would indicate previous centromere activity or a propensity for new centromere formation. Likewise, the conservation of specific sequence motifs or classes at EBs among divergent mammalian taxa has not been determined.</p> <p>Results</p> <p>To define conserved sequence features of EBs associated with centromere evolution, we performed comparative sequence analysis of more than 4.8 Mb within the tammar wallaby, <it>Macropus eugenii</it>, derived from centromeric regions (CEN), euchromatic regions (EU), and an evolutionary breakpoint (EB) that has undergone convergent breakpoint reuse and past centromere activity in marsupials. We found a dramatic enrichment for long interspersed nucleotide elements (LINE1s) and endogenous retroviruses (ERVs) and a depletion of short interspersed nucleotide elements (SINEs) shared between CEN and EBs. We analyzed the orthologous human EB (14q32.33), known to be associated with translocations in many cancers including multiple myelomas and plasma cell leukemias, and found a conserved distribution of similar repetitive elements.</p> <p>Conclusion</p> <p>Our data indicate that EBs tracked within the class Mammalia harbor sequence features retained since the divergence of marsupials and eutherians that may have predisposed these genomic regions to large-scale chromosomal instability.</p

A Fortuitous Syncope. The pitfalls of Integrated Bipolar Defibrillator Leads

Myopotential oversensing in implantable defibrillators causing inhibition of pacing and inappropriate therapies is well described. Current literature is dominated by reports of diaphragmatic muscle as the source of such far-field oversensing. Those reporting pectoral muscle sources were invariably due to unipolar sensing circuits, incorrect DF-1 connections or inappropriate programming. We report an interesting case of pectoral muscle myopotential oversensing causing inhibition of bradycardia pacing leading to presyncope and syncope

Mind the gap: quantification of incomplete ablation patterns after pulmonary vein isolation using minimum path search

Pulmonary vein isolation (PVI) is a common procedure for the treatment of atrial fibrillation (AF). A successful isolation produces a continuous lesion (scar) completely encircling the veins that stops activation waves from propagating to the atrial body. Unfortunately, the encircling lesion is often incomplete, becoming a combination of scar and gaps of healthy tissue. These gaps are potential causes of AF recurrence, which requires a redo of the isolation procedure. Late-gadolinium enhanced cardiac magnetic resonance (LGE-CMR) is a non-invasive method that may also be used to detect gaps, but it is currently a time-consuming process, prone to high inter-observer variability. In this paper, we present a method to semi-automatically identify and quantify ablation gaps. Gap quantification is performed through minimum path search in a graph where every node is a scar patch and the edges are the geodesic distances between patches. We propose the Relative Gap Measure (RGM) to estimate the percentage of gap around a vein, which is defined as the ratio of the overall gap length and the total length of the path that encircles the vein. Additionally, an advanced version of the RGM has been developed to integrate gap quantification estimates from different scar segmentation techniques into a single figure-of-merit. Population-based statistical and regional analysis of gap distribution was performed using a standardised parcellation of the left atrium. We have evaluated our method on synthetic and clinical data from 50 AF patients who underwent PVI with radiofrequency ablation. The population-based analysis concluded that the left superior PV is more prone to lesion gaps while the left inferior PV tends to have less gaps (p<0.05 in both cases), in the processed data. This type of information can be very useful for the optimization and objective assessment of PVI interventions

Research Inefficiency in Degenerative Cervical Myelopathy: Findings of a Systematic Review on Research Activity Over the Past 20 Years.

STUDY DESIGN: Scoping review. OBJECTIVE: To describe activity, themes and trends in degenerative cervical myelopathy (DCM) research over the past 20 years with a view to considering DCM research inefficiency. METHODS: A systematic review of MEDLINE and Embase for "Cervical" AND "Myelopathy" was conducted following PRISMA guidelines. Full-text papers in English, exclusively studying DCM, published between January 1, 1995 and December 31, 2015 were considered eligible. Country of origin, number of papers published, number of patients studied, research theme, and year of publication were assessed. Comparison was made between developed and developing countries. RESULTS: A total of 1485 papers and 4 117 051 patients were included. Japan published more papers (450) than any other country while the United States studied the greatest number of patients (3 674 737). Over 99.4% of papers and 78.6% of patients were from developed countries. The number of papers (r = 0.96, P < .001) and patients (r = 0.83 P < .001) studied each year increased significantly overall and for both developed (r = 0.93, P < .001; r = 0.81, P < .001) and developing countries (r = 0.90, P < .001; r = 0.87, P < .001). Surgery was the most prevalent theme (58.3% papers; 55.7% patients) for developed and developing countries. Research from developing countries showed greater thematic variability. CONCLUSIONS: DCM research activity is increasing internationally, with surgery remaining the focus. Research output has predominantly been from developed countries; however, the rate of growth for developed and developing countries is comparable

Comparative results of transluminal extraction coronary atherectomy in saphenous vein graft lesions with and without thrombus

AbstractObjectives. The purpose of this retrospective study was to compare the results of transluminal extraction coronary atherectomy in saphenous vein graft lesions with and without angiographic thrombus.Background. Percutaneous interventions in lesions with thrombus are associated with reduced procedural success and increased risk of complications. Use of the transluminal extraction catheter, which cuts and aspirates atheroma and thrombus, has been advocated as a potential revascularization strategy for lesions with thrombus.Methods. Baseline patient characteristics, lesion morphology, immediate angiographic results, in-hospital complications and follow-up were prospectively entered into an interventional cardiology data base. The results of transluminal extraction coronary atherectomy in saphenous vein bypass grafts with angiographic thrombus were compared with results in similar grafts without angiographic thrombus.Results. Transluminal extraction coronary atherectomy was performed in 175 patients with 183 vein graft lesions, including 59 lesions (32%) with thrombus (Group 1) and 124 (68%) without thrombus (Group 2). Compared with lesions in Group 2, lesions in Group 1 were associated with a higher incidence of baseline total occlusion, diffuse disease and abnormal Thrombolysis in Myocardial Infarction (TIMI) grade flow (p < 0.05); more severe diameter stenosis at baseline, after atherectomy and after final angiography (p < 0.05); a lower rate of clinical success (69% vs, 88%, p < 0.01); and more angiographic and clinical complications, including no reflow (p < 0.05), vascular repair (p < 0.05) and Q wave myocardial infarction (p = 0.09).Conclusions. In transluminal extraction coronary atherectomy of saphenous vein bypass grafts, the presence of thrombus is associated with more baseline lesion complexity, reduced clinical success and increased risk of no reflow, Q wave myocardial infarction and vascular repair

A Demonstration of using Partnerships and Private Lands Conservation to Evaluate Livestock Grazing as a Management Tool for Greater Sage Grouse in Central Montana

Partnerships across agencies and land ownerships established to maintain wildlife-compatible “working landscapes” are critical for conserving and managing wildlife in the West.  Preliminary results from the first three years of a 10-yr study in central Montana demonstrate this management approach.  We are evaluating prescribed grazing systems implemented by NRCS’s Sage Grouse Initiative (SGI) that are designed to improve hiding cover and food availability for Greater sage grouse (Centrocercus urophasianus) during critical life stages via voluntary, incentive-based modifications of livestock grazing management.  Extensive vegetation sampling across 8 SGI-enrolled ranches and 20 non-enrolled ranches in 2013 revealed significant increases in residual grass height, live grass height, and herbaceous vegetation cover on SGI-enrolled lands. In 2011-2013, we monitored adult female sage-grouse and chicks with radiotelemetry to measure vital rates and habitat use. Annual hen survival ranged from 57-74 percent, nest success ranged from 12-61 percent, and chick survival ranged from 9-23 percent.  Using an information theoretic approach in program MARK, the top-ranked nest success model showed that grass height was positively correlated with nest success.   During late nesting to early brood rearing periods of 2012 and 2013 we used pitfall traps to collected ground-dwelling arthropods from cattle grazed and rest-rotation phase pastures enrolled in the SGI program. Collected arthropods were identified and appropriate specimens were classified as sage grouse chick food items. During both years of study, food item catches were greatest (P &lt; 0.03) in rested versus grazed pastures indicating that strategic pasture rest may increase the availability of sage grouse chick food resources

Surface flattening of the human left atrium and proof-of-concept clinical applications

Surface flattening in medical imaging has seen widespread use in neurology and more recently in cardiology to describe the left ventricle using the bull's-eye plot. The method is particularly useful to standardize the display of functional information derived from medical imaging and catheter-based measurements. We hypothesized that a similar approach could be possible for the more complex shape of the left atrium (LA) and that the surface flattening could be useful for the management of patients with atrial fibrillation (AF). We implemented an existing surface mesh parameterization approach to flatten and unfold 3D LA models. Mapping errors going from 2D to 3D and the inverse were investigated both qualitatively and quantitatively using synthetic data of regular shapes and computer tomography scans of an anthropomorphic phantom. Testing of the approach was carried out using data from 14 patients undergoing ablation treatment for AF. 3D LA meshes were obtained from magnetic resonance imaging and electroanatomical mapping systems. These were unfolded using the developed approach and used to demonstrate proof-of-concept applications, such as the display of scar information, electrical information and catheter position. The work carried out shows that the unfolding of complex cardiac structures, such as the LA, is feasible and has several potential clinical uses for the management of patients with AF.</p

The cellular and synaptic architecture of the mechanosensory dorsal horn

The deep dorsal horn is a poorly characterized spinal cord region implicated in processing low-threshold mechanoreceptor (LTMR) information. We report an array of mouse genetic tools for defining neuronal components and functions of the dorsal horn LTMR-recipient zone (LTMR-RZ), a role for LTMR-RZ processing in tactile perception, and the basic logic of LTMR-RZ organization. We found an unexpectedly high degree of neuronal diversity in the LTMR-RZ: seven excitatory and four inhibitory subtypes of interneurons exhibiting unique morphological, physiological, and synaptic properties. Remarkably, LTMRs form synapses on between four and 11 LTMR-RZ interneuron subtypes, while each LTMR-RZ interneuron subtype samples inputs from at least one to three LTMR classes, as well as spinal cord interneurons and corticospinal neurons. Thus, the LTMR-RZ is a somatosensory processing region endowed with a neuronal complexity that rivals the retina and functions to pattern the activity of ascending touch pathways that underlie tactile perception

Novel system for real-time integration of 3-D echocardiography and fluoroscopy for image-guided cardiac interventions: Preclinical validation and clinical feasibility evaluation

© 2015 IEEE. Real-time imaging is required to guide minimally invasive catheter-based cardiac interventions. While transesophageal echocardiography allows for high-quality visualization of cardiac anatomy, X-ray fluoroscopy provides excellent visualization of devices. We have developed a novel image fusion system that allows real-time integration of 3-D echocardiography and the X-ray fluoroscopy. The system was validated in the following two stages: 1) preclinical to determine function and validate accuracy; and 2) in the clinical setting to assess clinical workflow feasibility and determine overall system accuracy. In the preclinical phase, the system was assessed using both phantom and porcine experimental studies. Median 2-D projection errors of 4.5 and 3.3 mm were found for the phantom and porcine studies, respectively. The clinical phase focused on extending the use of the system to interventions in patients undergoing either atrial fibrillation catheter ablation (CA) or transcatheter aortic valve implantation (TAVI). Eleven patients were studied with nine in the CA group and two in the TAVI group. Successful real-time view synchronization was achieved in all cases with a calculated median distance error of 2.2 mm in the CA group and 3.4 mm in the TAVI group. A standard clinical workflow was established using the image fusion system. These pilot data confirm the technical feasibility of accurate real-time echo-fluoroscopic image overlay in clinical practice, which may be a useful adjunct for real-time guidance during interventional cardiac procedures