Can smartphone wireless ECGs be used to accurately assess ECG intervals in pediatrics? A comparison of mobile health monitoring to standard 12-lead ECG

BACKGROUND:Arrhythmias in children are often paroxysmal, complicating the ability to capture the abnormal rhythm on routine ECG during an outpatient visit. The Alivecor Kardia Mobile (KM) device is a wireless mobile health (mHealth) device that generates a single lead ECG tracing with a FDA-approved algorithm for detection of atrial fibrillation in adults. OBJECTIVE:The goal of this study is to assess the accuracy of interval measurements on KM tracings by directly comparing to standard 12-lead ECGs in pediatric patients. METHODS:This single center, prospective study enrolled pediatric outpatients, age 20ms with 4/9 (44%) having a conduction disorder and 2/9 (22%) having marked sinus arrhythmia. Bland-Altman method of agreement demonstrated strong agreement for QRSd and QTc. The AF algorithm reported 4/30 (13%) false positive "possible AF" diagnoses (rhythm over-read on KM demonstrated n = 3 marked sinus arrhythmia, n = 1 sinus rhythm with aberrated PACs) resulting in a specificity of 87%. CONCLUSION:The Alivecor Kardia device produces accurate single lead ECG tracings in both healthy children and children with cardiac disease or rhythm abnormalities across the pediatric spectrum. This mHealth application provides an accurate, non-invasive, real-time approach for ambulatory ECG monitoring in children and adolescents

Force‐sensing catheters during pediatric radiofrequency ablation: The FEDERATION Study

Background Based on data from studies of atrial fibrillation ablations, optimal parameters for the TactiCath (TC; St. Jude Medical, Inc) force‐sensing ablation catheter are a contact force of 20 g and a force‐time integral of 400 g·s for the creation of transmural lesions. We aimed to evaluate TC in pediatric and congenital heart disease patients undergoing ablation. Methods and Results Comprehensive chart and case reviews were performed from June 2015 to March 2016. Of the 102 patients undergoing electrophysiology study plus ablation, 58 (57%) underwent ablation initially with a force‐sensing catheter. Patients had an average age of 14 (2.4–23) years and weight of 58 (18–195) kg with 15 patients having abnormal cardiac anatomy. Electrophysiology diagnoses for the + TC group included 30 accessory pathway–mediated tachycardia, 24 atrioventricular nodal reentrant tachycardia, and 7 other. Baseline generator settings included a power of 20 W, temperature of 40°, and 6 cc/min flow during lesion creation with 11 patients (19%) having alterations to parameters. Seventeen patients (30%) converted to an alternate ablation source. A total of 516 lesions were performed using the TC with a median contact force of 6 g, force‐time integral of 149 g·s, and lesion size index of 3.3. Median‐term follow‐up demonstrated 5 (10%) recurrences with no acute or median‐term complications. Conclusions TactiCath can be effectively employed in the treatment of pediatric patients with congenital heart disease with lower forces than previously described in the atrial fibrillation literature. Patients with atrioventricular nodal reentrant tachycardia or atrioventricular reciprocating tachycardia may not require transmural lesions and the TC may provide surrogate markers for success during slow pathway ablation. </jats:sec

Tissue-specific Splice Variants of HARE/Stabilin-2 are Expressed in Bone Marrow, Lymph Node, and Spleen

The hyaluronan receptor for endocytosis (HARE), or Stabilin-2, is the mammalian endocytic clearance receptor for HA, heparin, advanced glycation end-products, acetylated and oxidized low-density lipoproteins and collagen N-terminal propeptides. This large 2551 amino acid receptor is encoded by a gene that covers over 180 kbp on human chromosome 12 and is predicted to be composed of 69 exons. Due to the expression profile of this gene and the number of exons it contains, we hypothesized that splice variants of stab2 are encoded in these tissues. In addition, a correlation between alternative splice variants and cancer progression has been shown in other HA receptors such as RHAMM and CD42. In this study, two methods were utilized in identifying and/or isolating the HARE splice variants. The first method used primer sets to amplify the 190-HARE encoding region that could contain splice junctions; therefore, they could be removed from the gel, purified, and sequenced. Five splice variants were detected in that manner. In the second approach, the entire open reading frame of HARE was amplified. This allowed four splice variants with extensive exon splicing to be isolated. After the splice variants were sequenced, three were cloned into a mammalian expression vector. Next, stable cell lines expressing the variants were created in order to determine stable protein expression. In this study, the splice variants were found to be tissue specific in most cases. This means that tissue specific regulatory splicing mechanisms may lead to differences in functionality between the splice variants

3′-Processing and strand transfer catalysed by retroviral integrase in crystallo

Retroviral integrase (IN) is responsible for two consecutive reactions, which lead to insertion of a viral DNA copy into a host cell chromosome. Initially, the enzyme removes di- or trinucleotides from viral DNA ends to expose 3′-hydroxyls attached to the invariant CA dinucleotides (3′-processing reaction). Second, it inserts the processed 3′-viral DNA ends into host chromosomal DNA (strand transfer). Herein, we report a crystal structure of prototype foamy virus IN bound to viral DNA prior to 3′-processing. Furthermore, taking advantage of its dependence on divalent metal ion cofactors, we were able to freeze trap the viral enzyme in its ground states containing all the components necessary for 3′-processing or strand transfer. Our results shed light on the mechanics of retroviral DNA integration and explain why HIV IN strand transfer inhibitors are ineffective against the 3′-processing step of integration. The ground state structures moreover highlight a striking substrate mimicry utilized by the inhibitors in their binding to the IN active site and suggest ways to improve upon this clinically relevant class of small molecules

Percutaneous pulmonary valve implantation alters electrophysiologic substrate

BACKGROUND: Percutaneous pulmonary valve implantation (PPVI) is first‐line therapy for some congenital heart disease patients with right ventricular outflow tract dysfunction. The hemodynamics improvements after PPVI are well documented, but little is known about its effects on the electrophysiologic substrate. The objective of this study is to assess the short‐ and medium‐term electrophysiologic substrate changes and elucidate postprocedure arrhythmias. METHODS AND RESULTS: A retrospective chart review of patients undergoing PPVI from May 2010 to April 2015 was performed. A total of 106 patients underwent PPVI; most commonly these patients had tetralogy of Fallot (n=59, 55%) and pulmonary insufficiency (n=60, 57%). The median follow‐up time was 28 months (7‐63 months). Pre‐PPVI, 25 patients (24%) had documented arrhythmias: nonsustained ventricular tachycardia (NSVT) (n=9, 8%), frequent premature ventricular contractions (PVCs) (n=6, 6%), and atrial fibrillation/flutter (AF/AFL) (n=10, 9%). Post‐PPVI, arrhythmias resolved in 4 patients who had NSVT (44%) and 5 patients who had PVCs (83%). New arrhythmias were seen in 16 patients (15%): 7 NSVT, 8 PVCs, and 1 AF/AFL. There was resolution at medium‐term follow‐up in 6 (86%) patients with new‐onset NSVT and 7 (88%) patients with new‐onset PVCs. There was no difference in QRS duration pre‐PPVI, post‐PPVI, and at medium‐term follow‐up (P=0.6). The median corrected QT lengthened immediately post‐PPVI but shortened significantly at midterm follow‐up (P<0.01). CONCLUSIONS: PPVI reduced the prevalence of NSVT. The majority of postimplant arrhythmias resolve by 6 months of follow‐up

Analysis of the Copenhagen Accord pledges and its global climatic impacts‚ a snapshot of dissonant ambitions

This analysis of the Copenhagen Accord evaluates emission reduction pledges by individual countries against the Accord's climate-related objectives. Probabilistic estimates of the climatic consequences for a set of resulting multi-gas scenarios over the 21st century are calculated with a reduced complexity climate model, yielding global temperature increase and atmospheric CO2 and CO2-equivalent concentrations. Provisions for banked surplus emission allowances and credits from land use, land-use change and forestry are assessed and are shown to have the potential to lead to significant deterioration of the ambition levels implied by the pledges in 2020. This analysis demonstrates that the Copenhagen Accord and the pledges made under it represent a set of dissonant ambitions. The ambition level of the current pledges for 2020 and the lack of commonly agreed goals for 2050 place in peril the Accord's own ambition: to limit global warming to below 2 °C, and even more so for 1.5 °C, which is referenced in the Accord in association with potentially strengthening the long-term temperature goal in 2015. Due to the limited level of ambition by 2020, the ability to limit emissions afterwards to pathways consistent with either the 2 or 1.5 °C goal is likely to become less feasibl

Frontostriatal Maturation Predicts Cognitive Control Failure to Appetitive Cues in Adolescents

Adolescent risk-taking is a public health issue that increases the odds of poor lifetime outcomes. One factor thought to influence adolescents' propensity for risk-taking is an enhanced sensitivity to appetitive cues, relative to an immature capacity to exert sufficient cognitive control. We tested this hypothesis by characterizing interactions among ventral striatal, dorsal striatal, and prefrontal cortical regions with varying appetitive load using fMRI scanning. Child, teen, and adult participants performed a go/no-go task with appetitive (happy faces) and neutral cues (calm faces). Impulse control to neutral cues showed linear improvement with age, whereas teens showed a nonlinear reduction in impulse control to appetitive cues. This performance decrement in teens was paralleled by enhanced activity in the ventral striatum. Prefrontal cortical recruitment correlated with overall accuracy and showed a linear response with age for no-go versus go trials. Connectivity analyses identified a ventral frontostriatal circuit including the inferior frontal gyrus and dorsal striatum during no-go versus go trials. Examining recruitment developmentally showed that teens had greater between-subject ventral-dorsal striatal coactivation relative to children and adults for happy no-go versus go trials. These findings implicate exaggerated ventral striatal representation of appetitive cues in adolescents relative to an intermediary cognitive control response. Connectivity and coactivity data suggest these systems communicate at the level of the dorsal striatum differentially across development. Biased responding in this system is one possible mechanism underlying heightened risk-taking during adolescence

A corepressor participates in LexA-independent regulation of error-prone polymerases in Acinetobacter

The DNA damage response of the multidrug-resistant pathogen Acinetobacter baumannii, which induces mutagenic UmuD′2C error-prone polymerases, differs from that of many bacteria. Acinetobacter species lack a LexA repressor, but induce gene transcription after DNA damage. One regulator, UmuDAb, binds to and represses the promoters of the multiple A. baumannii ATCC 17978 umuDC alleles and the divergently transcribed umuDAb and ddrR genes. ddrR is unique to the genus Acinetobacter and of unknown function. 5\u27 RACE (rapid amplification of cDNA ends) PCR mapping of the umuDAb and ddrR transcriptional start sites revealed that their −35 promoter elements overlapped the UmuDAb binding site, suggesting that UmuDAb simultaneously repressed expression of both genes by blocking polymerase access. This coordinated control of ddrR and umuDAb suggested that ddrR might also regulate DNA damage-inducible gene transcription. RNA-sequencing experiments in 17 978 ddrR− cells showed that ddrR regulated approximately 25 % (n=39) of the mitomycin C-induced regulon, with umuDAb coregulating 17 of these ddrR-regulated genes. Eight genes (the umuDC polymerases, umuDAb and ddrR) were de-repressed in the absence of DNA damage, and nine genes were uninduced in the presence of DNA damage, in both ddrR and umuDAb mutant strains. These data suggest ddrR has multiple roles, both as a co-repressor and as a positive regulator of DNA damage-inducible gene transcription. Additionally, 57 genes were induced by mitomycin C in the ddrR mutant but not in wild-type cells. This regulon contained multiple genes for DNA replication, recombination and repair, transcriptional regulators, RND efflux, and transport. This study uncovered another regulator of the atypical DNA damage response of this genus, to help describe how this pathogen acquires drug resistance through its expression of the error-prone polymerases under DdrR and UmuDAb control

Computing Garsia Entropy for Bernoulli Convolutions with Algebraic Parameters

We introduce a parameter space containing all algebraic integers $\beta\in(1,2]$ that are not Pisot or Salem numbers, and a sequence of increasing piecewise continuous function on this parameter space which gives a lower bound for the Garsia entropy of the Bernoulli convolution $\nu_{\beta}$. This allows us to show that $\mathrm{dim}_\mathrm{H} (\nu_{\beta})=1$ for all $\beta$ with representations in certain open regions of the parameter space.Comment: 21 pages, 2 figures, 5 table

Analysis of milling of dry compacted ribbons by distinct element method

Fine cohesive powders are often dry granulated to improve their flowability. Roller compaction is commonly used to produce dense ribbons which are then milled. The material properties of the powder and the conditions in the roller compactor affect the strength of the ribbons, however there is no method in the literature to predict the size distribution of the product of ribbon milling. Here we introduce a method, by using the Distinct Element Method (DEM) to determine the prevailing impact velocities and stresses in the mill, with bonded spheres representing the ribbons. The bond strength is calibrated by matching experimental results of three point bend measurements and predictions from numerical simulations. The ribbons are then exposed to the dynamic conditions predicted by the DEM, by dropping them from a controlled height to cause fragmentation, and subsequently stressing them in a shear cell under the conditions again predicted by the DEM. The fragments are sheared under these conditions to represent repeated passage of bars over the fragments at the mill base. Sieve analysis is used here to determine the particle size distribution under given mill conditions. The predicted size distribution of the mill product compares well with the plant data. It is found that the mill speed and length of ribbons fed to the mill have no significant influence on the product size distribution for the range tested