Bayesian models for syndrome- and gene-specific probabilities of novel variant pathogenicity

BACKGROUND: With the advent of affordable and comprehensive sequencing technologies, access to molecular genetics for clinical diagnostics and research applications is increasing. However, variant interpretation remains challenging, and tools that close the gap between data generation and data interpretation are urgently required. Here we present a transferable approach to help address the limitations in variant annotation. METHODS: We develop a network of Bayesian logistic regression models that integrate multiple lines of evidence to evaluate the probability that a rare variant is the cause of an individual's disease. We present models for genes causing inherited cardiac conditions, though the framework is transferable to other genes and syndromes. RESULTS: Our models report a probability of pathogenicity, rather than a categorisation into pathogenic or benign, which captures the inherent uncertainty of the prediction. We find that gene- and syndrome-specific models outperform genome-wide approaches, and that the integration of multiple lines of evidence performs better than individual predictors. The models are adaptable to incorporate new lines of evidence, and results can be combined with familial segregation data in a transparent and quantitative manner to further enhance predictions. Though the probability scale is continuous, and innately interpretable, performance summaries based on thresholds are useful for comparisons. Using a threshold probability of pathogenicity of 0.9, we obtain a positive predictive value of 0.999 and sensitivity of 0.76 for the classification of variants known to cause long QT syndrome over the three most important genes, which represents sufficient accuracy to inform clinical decision-making. A web tool APPRAISE [http://www.cardiodb.org/APPRAISE] provides access to these models and predictions. CONCLUSIONS: Our Bayesian framework provides a transparent, flexible and robust framework for the analysis and interpretation of rare genetic variants. Models tailored to specific genes outperform genome-wide approaches, and can be sufficiently accurate to inform clinical decision-making

Inclusive and Direct Photons in S + Au Central Collisions at 200A GeV/c

A hadron and string cascade model, JPCIAE, which is based on LUND string model, PYTHIA event generator especially, is used to study both inclusive photon production and direct photon production in 200A GeV S + Au central collisions. The model takes into account the photon production from the partonic QCD scattering process, the hadronic final-state interaction, and the hadronic decay and deals with them consistently. The results of JPCIAE model reproduce successfully both the WA93 data of low p_T inclusive photon distribution and the WA80 data of transverse momentum dependent upper limit of direct photon. The photon production from different decay channels is investigated for both direct and inclusive photons. We have discussed the effects of the partonic QCD scattering and the hadronic final-state interaction on direct photon production as well.Comment: 6 pages with 5 figure

Utilização do efeito macho para induzir e sincronizar os estros (Cios) de fêmeas ovinas.

Introdução. Ciclo reprodutivo de ovelha. Efeito macho e fisiologia reprodutiva de ovinos. Efeito macho e a concentração de parições em regiões com diferentes latitudes. Sincronização dos estros (Cios) em ovelhas. Indução do estro (Cio) no período de anestro sazonal. Considerações finais.bitstream/item/78022/1/Cristiane-Sa-CTE99.pd

Emergent Quantum Near-Criticality from Baryonic Black Branes

We find new black 3-brane solutions describing the "conifold gauge theory" at nonzero temperature and baryonic chemical potential. Of particular interest is the low-temperature limit where we find a new kind of weakly curved near-horizon geometry; it is a warped product AdS_2 x R^3 x T^{1,1} with warp factors that are powers of the logarithm of the AdS radius. Thus, our solution encodes a new type of emergent quantum near-criticality. We carry out some stability checks for our solutions. We also set up a consistent ansatz for baryonic black 2-branes of M-theory that are asymptotic to AdS_4 x Q^{1,1,1}.Comment: 29 pages, 4 figures; v2 discussion of entropy revised, minor changes; v3 note added, minor improvements, version published in JHE

Effect of visual feedback on the occipital-parietal-motor network in Parkinson's disease with freezing of gait.

Freezing of gait (FOG) is an elusive phenomenon that debilitates a large number of Parkinson's disease (PD) patients regardless of stage of disease, medication status, or deep brain stimulation implantation. Sensory feedback cues, especially visual feedback cues, have been shown to alleviate FOG episodes or even prevent episodes from occurring. Here, we examine cortical information flow between occipital, parietal, and motor areas during the pre-movement stage of gait in a PD-with-FOG patient that had a strong positive behavioral response to visual cues, one PD-with-FOG patient without any behavioral response to visual cues, and age-matched healthy controls, before and after training with visual feedback. Results for this case study show differences in cortical information flow between the responding PD-with-FOG patient and the other two subject types, notably, an increased information flow in the beta range. Tentatively suggesting the formation of an alternative cortical sensory-motor pathway during training with visual feedback, these results are proposed as subject for further verification employing larger cohorts of patients

Hidden Quantum Critical Point in a Ferromagnetic Superconductor

We consider a coexistence phase of both Ferromagnetism and superconductivity and solve the self-consistent mean-field equations at zero temperature. The superconducting gap is shown to vanish at the Stoner point whereas the magnetization doesn't. This indicates that the para-Ferro quantum critical point becomes a hidden critical point. The effective mass in such a phase gets enhanced whereas the spin wave stiffness is reduced as compared to the pure FM phase. The spin wave stiffness remains finite even at the para-Ferro quantum critical point.Comment: 4 pages, Phys. Rev. B (Rapid) accepte

Emission Characteristics of the Projectile Fragments at Relativistic Energy

A projectile (84^Kr_36) having kinetic energy around 1 A GeV was used to expose NIKFI BR-2 emulsion target. A total of 700 inelastic events are used in the present studies on projectile fragments. The emission angle of the projectile fragments are strongly affected by charge of the other projectile fragments emitted at same time with different emission angle is observed. The angular distribution studies show symmetrical nature for lighter charge projectile fragments. The symmetrical nature decreased with the charge of projectile fragments. At ~4o of emission angle for double charge projectile fragments, the momentum transfer during interaction is similar for various target species of emulsion were observed. We also observed a small but significant amplitude peaks on both side of the big peak for almost all light charge projectile fragments having different delta angle values. It reflects that there are few percent of projectile fragments that are coming from the decay of heavy projectile fragments or any other process.Comment: 32 pages, 17 Figure