Diagnosis of right bundle branch block: a concordance study

Bundle branch block; ConcordanceBloqueig de branca; ConcordançaBloqueo de rama; ConcordanciaBACKGROUND: Right bundle branch block is one of the most common electrocardiographic abnormalities. Most cases of right bundle branch block are detected in asymptomatic patients in primary care, so a correct interpretation of electrocardiograms (ECGs) at this level is necessary. The objective of this research is to determine the degree of concordance in the diagnosis of incomplete and complete right bundle branch block between four primary care researchers and a cardiologist. METHODS: The research design is a retrospective cohort study of patients over 18 years of ages of patients over 18 years of ages who underwent an ECG for any reason and were diagnosed with right bundle branch block by their physician. The physicians participating, 4 primary care researchers and a cardiologist were specialized in interpreting electrocardiographic records. The diagnosis of incomplete and complete right bundle branch block was recorded and other secondary variables were analysed. In case of diagnostic discordance between the researchers, the ECGs were reviewed by an expert cardiologist, who interpreted them, established the diagnosis and analysed the possible causes for the discrepancy. RESULTS: We studied 160 patients diagnosed with right bundle branch block by their general practise. The patients had a mean age of 64.8 years and 54% of them were men. The concordance in the diagnosis of incomplete right bundle branch block showed a Fleiss' kappa index (k) of 0.71 among the five researchers and of 0.85 among only the primary care researchers. The k for complete right bundle branch block was 0.93 among the five researchers and 0.96 among only the primary care researchers. CONCLUSION: The interobserver agreement in the diagnosis of right bundle branch block performed by physicians specialized in ECG interpretation (primary care physicians and a cardiologist) was very good. The variability was greater for the diagnosis of incomplete right bundle branch block

Persistent atrial fibrillation hierarchical activation: from highest DF sites to wave fractionation at the boundaries

Preclinical studies showed a relationship between high dominant frequency areas (HDFA) and wave fractionation, but evidence in patient who atrial fibrillation (AF) persists for long-term periods (persAF) it is not well defined. This study aims to assess the spatiotemporal organization characteristics at HDFAs is persAF and its impact after per standard pulmonary vein isolation (PVI). Eight persAF patients had a non-contact array catheter deployed into the left atrium to collect up to 2048 AF electrograms (AEG) for 15 s. AEGs were band-pass filtered (3-30 Hz) followed by ventricular farfield cancellation. DF between 4-10 Hz and its respective organization index (OI) were calculated (4 s with 50% overlap) to produce 3D DF and OI maps. HDFA defined as the regions within a 0.25 Hz drop from the highest DF were determined and their centre of gravity (CG) calculated. Highest DF sites showed a higher OI at their core when compared to the periphery (0.422±0.101 vs. 0.386±0.126, p=0.02) and increased again organization at sites distant from the HDFAs. Similarly, after PVI, OI remained higher as compared to their periphery (0.372±0.026 vs. 0.332±0.036, p=0.22), but with significant lower values when compared with baseline (p<0.0001). PersAF patients showed higher organization in the HDFAs core when compared with its periphery

An SiO Toroid and Wide-angle Outflow associated with the Massive Protostar W75N(B)-VLA2

We have carried out ALMA observations of the massive star-forming region W75N(B), which contains the massive protostars VLA1, VLA2, and VLA3. Particularly, VLA2 is an enigmatic protostar associated with a wind-driven H$_2$O maser shell, which has evolved from an almost isotropic outflow to a collimated one in just 20 years. The shell expansion seemed to be halted by an obstacle located to the northeast of VLA2. Here we present our findings from observing the 1.3 mm continuum and H$_2$CO and SiO emission lines. Within a region of $\sim 30"$ ($\sim 39,000$ au) diameter, we have detected 40 compact mm-continuum sources, three of them coinciding with VLA1, VLA2, and VLA3. While the H$_2$CO emission is mainly distributed in a fragmented structure around the three massive protostars, but without any of the main H$_2$CO clumps spatially coinciding with them, the SiO is highly concentrated on VLA2, indicating the presence of very strong shocks generated near this protostar. The SiO emission is clearly resolved into an elongated structure ($\sim 0.6"\times0.3"$; $\sim 780$ au$\times$390 au) perpendicular to the major axis of the wind-driven maser shell. The structure and kinematics of the SiO emission are consistent with a toroid and a wide-angle outflow surrounding a central mass of $\sim 10$ M$_{\odot}$, thus supporting previous theoretical predictions regarding the evolution of the outflow. Additionally, we have identified the expected location and estimated the gas density of the obstacle that is hindering the expansion of the maser shell.Comment: To be published in The Astrophysical Journal Letters. Sixteen pages, seven figures. Updated metadat

Balance between sodium and calcium currents underlying chronic atrial fibrillation termination: An in silico intersubject variability study

BACKGROUND Atrial remodeling as a result of long-standing persistent atrial fibrillation (AF) induces substrate modifications that lead to different perpetuation mechanisms than in paroxysmal AF and a reduction in the efficacy of antiarrhythmic treatments. OBJECTIVE The purpose of this study was to identify the ionic current modifications that could destabilize reentries during chronic AF and serve to personalize antiarrhythmic strategies. METHODS A population of 173 mathematical models of remodeled human atrial tissue with realistic intersubject variability was developed based on action potential recordings of 149 patients diagnosed with AF. The relationship of each ionic current with AF maintenance and the dynamics of functional reentries (rotor meandering, dominant frequency) were evaluated by means of 3-dimensional simulations. RESULTS Self-sustained reentries were maintained in 126 (73%) of the simulations. AF perpetuation was associated with higher expressions of I-Na and I-caL (P < .01), with no significant differences in the remaining currents. I-caL blockade promoted AF extinction in 30% of these 126 models. The mechanism of AF termination was related with collisions between rotors because of an increase in rotor meandering (1.71 +/- 2.01cm(2)) and presented an increased efficacy in models with a depressed INa (P < .01). CONCLUSION Mathematical simulations based on a population of models representing intersubject variability allow the identification of ionic mechanisms underlying rotor dynamics and the definition of new personalized pharmacologic strategies. Our results suggest that the underlying mechanism of the diverging success of I-caL block as an antiarrhythmic strategy is dependent on the basal availability of sodium and calcium ion channel conductivities.Supported by the Spanish Ministry of Education (FPU2010); the Wellcome Trust Fellowship 100246/Z/12/Z; Universitat Politecnica de Valencia; the Spanish Health Research Fund (PI13/00903); the Spanish Society of Cardiology; the Spanish Ministry of Science; Generalitat Valenciana Grants (ACIF/2013/021); and Innovation (Red RIC, PLE2009-0152). Drs. Rodriguez and Climent are equally contributing senior authors.Liberos Mascarell, A.; Bueno-Orovio, A.; Rodrigo Bort, M.; Ravens, U.; Hernández-Romero, I.; Fernández-Avilés, F.; Guillem Sánchez, MS.... (2016). Balance between sodium and calcium currents underlying chronic atrial fibrillation termination: An in silico intersubject variability study. Heart Rhythm. 13(12):2358-2365. https://doi.org/10.1016/j.hrthm.2016.08.028S23582365131

Mediterranean, DASH, and MIND Dietary Patterns and Cognitive Function: The 2-Year Longitudinal Changes in an Older Spanish Cohort

Background and Aims: Plant-forward dietary patterns have been associated with cardiometabolic health benefits, which, in turn, have been related to cognitive performance with inconsistent findings. The objective of this study was to examine the relationship between baseline adherence to three a priori dietary patterns (Mediterranean, DASH, and MIND diets) with 2-year changes in cognitive performance in older adults with overweight or obesity and high cardiovascular disease risk. Methods: A prospective cohort analysis was conducted within the PREDIMED-Plus trial, involving 6,647 men and women aged 55-75 years with overweight or obesity and metabolic syndrome. Using a validated, semiquantitative 143-item food frequency questionnaire completed at baseline, the dietary pattern adherence scores were calculated. An extensive neuropsychological test battery was administered at baseline and 2-year follow-up. Multivariable-adjusted linear regression models were used to assess associations between 2-year changes in cognitive function z-scores across tertiles of baseline adherence to the a priori dietary patterns. Results: Adherence to the Mediterranean diet at baseline was associated with 2-year changes in the general cognitive screening Mini-Mental State Examination (MMSE, β: 0.070; 95% CI: 0.014, 0.175, P-trend = 0.011), and two executive function-related assessments: the Trail Making Tests Part A (TMT-A, β: −0.054; 95% CI: −0.110, − 0.002, P-trend = 0.047) and Part B (TMT-B, β: −0.079; 95% CI: −0.134, −0.024, P-trend = 0.004). Adherence to the MIND diet was associated with the backward recall Digit Span Test assessment of working memory (DST-B, β: 0.058; 95% CI: 0.002, 0.114, P-trend = 0.045). However, higher adherence to the DASH dietary pattern was not associated with better cognitive function over a period of 2 years. Conclusion: In older Spanish individuals with overweight or obesity and at high cardiovascular disease risk, higher baseline adherence to the Mediterranean dietary pattern may be associated with better cognitive performance than lower adherence over a period of 2 years

Mismatch repair-deficient rectal cancer and resistance to neoadjuvant chemotherapy

Purpose: Evaluate response of mismatch repair deficient (dMMR) rectal cancer to neoadjuvant chemotherapy. Experimental Design: dMMR rectal tumors at Memorial Sloan Kettering were retrospectively reviewed for characteristics, treatment, and outcomes. Fifty dMMR rectal cancer patients were identified by immunohistochemistry and/or microsatellite instability analysis, with initial treatment response compared to a matched pMMR rectal cancer cohort. Germline and somatic mutation analyses were evaluated. Patient-derived dMMR rectal tumoroids were assessed for chemotherapy sensitivity. Results: Of 21 patients receiving neoadjuvant chemotherapy (fluorouracil/oxaliplatin), 6 (29%) had progression of disease. In comparison, no progression was noted in 63 pMMR rectal tumors (P = 0.0001). Rectal cancer dMMR tumoroids reflected this resistance to chemotherapy. No genomic predictors of chemotherapy response were identified. Of 16 patients receiving chemoradiation, 13 (93%) experienced tumor downstaging; one patient had stable disease, comparable to 48 pMMR rectal cancers. Of 13 patients undergoing surgery, 12 (92%) had early-stage disease. Forty-two (84%) of the 50 patients tested positive for Lynch syndrome (LS) with enrichment of germline MSH2 and MSH6 mutations when compared to 193 LS-associated colon cancer patients (MSH2, 57% vs 36%; MSH6, 17% vs 9%; P &lt; .003). Conclusions: Over one-fourth of dMMR rectal tumors treated with neoadjuvant chemotherapy exhibited disease progression. Conversely, dMMR rectal tumors were sensitive to chemoradiation. MMR status should be performed upfront in all locally advanced rectal tumors with careful monitoring for response on neoadjuvant chemotherapy and genetic testing for LS in dMMR rectal cancer patients

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

VHE γ-ray discovery and multiwavelength study of the blazar 1ES 2322-409

A hotspot at a position compatible with the BL Lac object 1ES 2322-409 was serendipitously detected with H.E.S.S. during observations performed in 2004 and 2006 on the blazar PKS 2316-423. Additional data on 1ES 2322-409 were taken in 2011 and 2012, leading to a total live-time of 22.3 h. Point-like very-high-energy (VHE; E> 100 GeV) γ-ray emission is detected from a source centred on the 1ES 2322-409 position, with an excess of 116.7 events at a significance of 6.0σ. The average VHE γ-ray spectrum is well described with a power law with a photon index Γ = 3.40 ± 0.66stat ± 0.20sys and an integral flux Φ (E> 200 GeV) = (3.11± 0.71_stat± 0.62_sys)× 10^{-12} cm^{-2} s^{-1}, which corresponds to 1.1 {{ per cent}} of the Crab nebula flux above 200 GeV. Multiwavelength data obtained with Fermi LAT, Swift XRT and UVOT, RXTE PCA, ATOM, and additional data from WISE, GROND, and Catalina are also used to characterize the broad-band non-thermal emission of 1ES 2322-409. The multiwavelength behaviour indicates day-scale variability. Swift UVOT and XRT data show strong variability at longer scales. A spectral energy distribution (SED) is built from contemporaneous observations obtained around a high state identified in Swift data. A modelling of the SED is performed with a stationary homogeneous one-zone synchrotron-self-Compton leptonic model. The redshift of the source being unknown, two plausible values were tested for the modelling. A systematic scan of the model parameters space is performed, resulting in a well-constrained combination of values providing a good description of the broad-band behaviour of 1ES 2322-409