Rare truncating variants in the sarcomeric protein titin associate with familial and early-onset atrial fibrillation

Common genetic variants in structural proteins contribute to risk of atrial fibrillation (AF). Here, using whole-exome sequencing, the authors identify rare truncating variants in TTN that associate with familial and early-onset AF and show defects in cardiac sarcomere assembly in ttn.2-mutant zebrafish

A hybrid CS-SA intelligent approach to solve uncertain dynamic facility layout problems considering dependency of demands

Abstract This paper aims at proposing a quadratic assignment-based mathematical model to deal with the stochastic dynamic facility layout problem. In this problem, product demands are assumed to be dependent normally distributed random variables with known probability density function and covariance that change from period to period at random. To solve the proposed model, a novel hybrid intelligent algorithm is proposed by combining the simulated annealing and clonal selection algorithms. The proposed model and the hybrid algorithm are verified and validated using design of experiment and benchmark methods. The results show that the hybrid algorithm has an outstanding performance from both solution quality and computational time points of view. Besides, the proposed model can be used in both of the stochastic and deterministic situations

The relationship between transorbital ultrasound measurement of the optic nerve sheath diameter (ONSD) and invasively measured ICP in children

Purpose: The aim of this study was to investigate the relationship between optic nerve sheath diameter (ONSD) measurement and invasively measured intracranial pressure (ICP) in children. Methods: ONSD measurement was performed prior to invasive measurement of ICP. The mean binocular ONSD measurement was compared to the ICP reading. Physiological variables including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse rate, temperature, respiratory rate and end tidal carbon dioxide (ETCO2) level were recorded at the time of ONSD measurement. Diagnostic accuracy analysis was performed at various ICP thresholds and repeatability, intra- and inter-observer variability, correlation between measurements in different imaging planes as well the relationship over the entire patient cohort were examined in part I of this study. Results: Data from 174 patients were analysed. Repeatability and intra-observer variability were excellent (α = 0.97–0.99). Testing for inter-observer variability revealed good correlation (r = 0.89, p < 0.001). Imaging in the sagittal plane demonstrated a slightly better correlation with ICP (r = 0.66, p < 0.001). The ONSD measurement with the best diagnostic accuracy for detecting an ICP ≥ 20 mmHg over the entire patient cohort was 5.5 mm, sensitivity 93.2 %, specificity 74 % and odds ratio (OR) of 39.3. Conclusion: Transorbital ultrasound measurement of the OSND is a reliable and reproducible technique, demonstrating a good relationship with ICP and high diagnostic accuracy for detecting raised ICP