Search

The introduction of rapid exome sequencing (rES) for critically ill neonates admitted to the neonatal intensive care unit has made it possible to impact clinical decision-making. Unbiased prospective studies to quantify the impact of rES over routine genetic testing are, however, scarce. We performed a clinical utility study to compare rES to conventional genetic diagnostic workup for critically ill neonates with suspected genetic disorders. In a multicenter prospective parallel cohort study involving five Dutch NICUs, we performed rES in parallel to routine genetic testing for 60 neonates with a suspected genetic disorder and monitored diagnostic yield and the time to diagnosis. To assess the economic impact of rES, healthcare resource use was collected for all neonates. rES detected more conclusive genetic diagnoses than routine genetic testing (20% vs. 10%, respectively), in a significantly shorter time to diagnosis (15 days (95% CI 10–20) vs. 59 days (95% CI 23–98, p < 0.001)). Moreover, rES reduced genetic diagnostic costs by 1.5% (€85 per neonate). Conclusion: Our findings demonstrate the clinical utility of rES for critically ill neonates based on increased diagnostic yield, shorter time to diagnosis, and net healthcare savings. Our observations warrant the widespread implementation of rES as first-tier genetic test in critically ill neonates with disorders of suspected genetic origin.What is Known:• Rapid exome sequencing (rES) enables diagnosing rare genetic disorders in a fast and reliable manner, but retrospective studies with neonates admitted to the neonatal intensive care unit (NICU) indicated that genetic disorders are likely underdiagnosed as rES is not routinely used.• Scenario modeling for implementation of rES for neonates with presumed genetic disorders indicated an expected increase in costs associated with genetic testing.What is New:• This unique prospective national clinical utility study of rES in a NICU setting shows that rES obtained more and faster diagnoses than conventional genetic tests.• Implementation of rES as replacement for all other genetic tests does not increase healthcare costs but in fact leads to a reduction in healthcare costs.

The semi-leptonic transition of B¯s→Ds2ℓν¯ to tensor meson of negative parity JP=2− is examined in the content of the QCD sum rules approach. The three-point correlation function is used to calculate the transition form-factors of the hadronic matrix element involved in these channels. With these transition form-factors, the predicted branching ratios are estimated as: BR[B¯s→Ds2eν¯e]=4.32−2.0+2.0×10−3, BR[B¯s→Ds2μν¯μ]=4.29−2.0+2.0×10−3, and BR[B¯s→Ds2τν¯τ]=3.1−1.4+1.4×10−4. We also calculated the leptonic angular spectra and leptonic forward-backward asymmetries. The effect of the leptonic decay constant fDs2 on these observables is also considered. The obtained orders of the branching ratios in this work are indicating that these channels can be investigated at LHCb in the near future.

By using the quark part of the energy-momentum tensor current, the gravitational formfactors of the ρ, π, and K mesons are calculated within the light-cone sum rules method. In the considered version, the energy-momentum tensor current is not conserved and as a result, for integer spin J, there appear 4J+2 (2J+1) formfactors, which correspond to the conservation (nonconservation) of the energy-momentum tensor current. The average mass radius of ρ, π, and K mesons as well as the gravitational quadrupole moment of the ρ meson are calculated. We also compare our results with the one existing in the literature on these quantities.

By using the quark part of the energy-momentum tensor current, the gravitational formfactors of the $ \rho $ meson are calculated within the light-cone sum rules method. In the considered version, the energy-momentum tensor current is not conserved and as a result, there appear nine formfactors, six (three) of which correspond to the conservation (nonconservation) of the energy-momentum tensor current. We also compare our results with the one existing in the literature., Comment: Edit 1: Added Ref. [12] Edit 2: Added new references

The form factors of γ*N→Δ(1600) transition is calculated within the light-cone sum rules assuming that Δ+(1600) is the first radial excitation of Δ(1232). The Q2 dependence of the magnetic dipole G˜M(Q2), electric quadrupole G˜E(Q2), and Coulomb quadrupole G˜c(Q2) form factors are investigated. Moreover, the Q2 dependence of the ratios REM=−G˜E(Q2)G˜M(Q2) and RSM=−14mΔ(1600)24mΔ(1600)2Q2+(mΔ(1600)2−Q2−mN2)2G˜c(Q2)G˜M(Q2) are studied. Finally, our predictions on G˜M(Q2), G˜E(Q2), and G˜C(Q2) are compared with the results of other theoretical approaches.

Magnetic dipole moments of the negative parity light and heavy tensor mesons are calculated within the light cone QCD sum rules method. The results are compared with the positive parity counterparts of the corresponding tensor mesons. The results of the analysis show that the magnetic dipole moments of the negative parity light mesons are smaller compared to those of the positive parity mesons. Contrary to the light meson case, magnetic dipole moments of the negative parity heavy mesons are larger than the ones for the positive parity mesons.

The form-factors for the transition N*(1535)→N induced by isovector and isoscalar axial currents within the framework of light cone QCD sum rules by using the most general form of the interpolating current are calculated. In numerical calculations, we use two sets of values of input parameters. It is observed that the Q2 dependence of the form-factor GA can be described by the dipole form. Moreover, the form-factors GP(S) are found to be highly sensitive to the variations in the auxiliary parameter β. The numerical calculations show that the form factor GT(S) at all values of Q2 and β for both sets of values of the parameters are smaller than that one for GA(S) and GS(S).

The form factors of the $$\Lambda _{b} \rightarrow N^*\ell ^+ \ell ^-$$ Λb→N∗ℓ+ℓ- decay are calculated in the framework of the light cone QCD sum rules. In the calculations the contribution of the negative parity $$\Lambda _b^*$$ Λb∗ baryon is eliminated by constructing the sum rules for different Lorentz structures. Furthermore the branching ratio of the semileptonic $$\Lambda _b \rightarrow N^*\ell ^+ \ell ^-$$ Λb→N∗ℓ+ℓ- decay is calculated. The numerical study for the branching ratio of the $$\Lambda _{b} \rightarrow N^*\ell ^+ \ell ^-$$ Λb→N∗ℓ+ℓ- decay indicates that it is quite large and could be measurable at future planned experiments to be conducted at LHCb.

Form factors of the rare Λb(Λb*)→Nℓ+ℓ− decays are calculated in the framework of the light cone QCD sum rules by taking into account the contributions from the negative parity baryons. Using the obtained results on the form factors, the branching ratios of the considered decays are estimated. The numerical survey for the branching ratios of the Λb→Nℓ+ℓ− and Λb*→Nℓ+ℓ− decays indicate that these transitions could be measurable in LHCb in near future. Comparison of our predictions on the form factors and branching ratios with those existing in the literature is also performed.

Form factors of the rare $\Lambda_{b}(\Lambda_{b}^*)\to N\ell^{+}\ell^{-}$ decays are calculated in the framework of the light cone QCD sum rules by taking into account of the contributions from the negative parity baryons. Using the obtained results on the form factors, the branching ratios of the considered decays are estimated. The numerical survey for the branching ratios of the $\Lambda_b \rar N\ell^+\ell^- $ and $\Lambda_b^\ast \rar N\ell^+\ell^- $ decays indicate that these transitions could be measurable in LHCb in near future. Comparison of our predictions on the form factors and branching ratios with those existing in the literature is also performed., Comment: 18 pages, 4 figures, LaTeX formatted

For the design of the grain-processing stations of spacecrafts, such as EXOMARS 2020, reliable estimates are required on the internal and bulk flow characteristics of granular media under the low gravitational environments. Using theoretical and computational modelling, here we present results on the generic flow behaviour of granular materials through flow channels under different gravity levels. For this, we use three approaches, viz., (i) a simple one-dimensional discrete layer approach (DLA) based on hybrid-Lagrange continuum analysis (ii) three dimensional Kirya structural continuum model and (iii) three dimensional discrete element modelling (DEM). Each model has its merits and limitations. For the granular simulant considered here, a good level of agreement is obtained between the results of Kirya model and DEM simulations on the flow properties of the grains. Some qualitative comparisons are also reported favourably on the flow characteristics of grains between the results of the experimental parabolic flight campaign and the DEM simulations. The theoretical and DEM simulations presented here could help to minimise relying on the complex experimental programmes, such as the parabolic flight campaign, for evaluating the processing behaviour of grains under low gravitational environments in future.

The rare exclusive dileptonic decays are investigated in the general two-Higgs-doublet model of type III. A significant enhancement to the branching ratios, differential branching ratios, leptons forward–backward asymmetry, and the baryon polarizations over the standard model is obtained. Measurements of these quantities will be useful for establishing the two-Higgs doublet model.

In humans and other mammals, female cells carry two X-chromosomes, whereas male cells carry a single X and Y-chromosome. To achieve an equal expression level of X-linked genes in both sexes, a dosage compensation mechanism evolved, which results in transcriptional silencing of one X-chromosome in females. X chromosome inactivation (XCI) is random with respect to the parental origin of the X, occurs early during embryonic development, and is then stably maintained through a near infinite number of cell divisions. As a result of this, every female individual consists of a mosaic of two different cell populations, in which either the maternally or paternally derived X-chromosome is inactivated. As the X-chromosome harbors more than a thousand genes, of which many are implicated in human disease when mutated, this mosaicism has important disease implications. Whereas X-linked disorders are usually more severe in hemizygous males harboring a single X-chromosome, a more variable phenotype is observed in females. This variability is a direct consequence of the XCI-mosaicism, and is affected by the randomness of the XCI process. Here we review the latest insights into the regulation of this important female specific process, and discuss mechanisms that influence mosaicism in females, with a focus on the clinical consequences related to X-linked diseases in females.

Magnetic dipole moments of the negative parity light and heavy tensor mesons are calculated within the light cone QCD sum rules method. The results are compared with the positive parity counterparts of the corresponding tensor mesons. The results of the analysis show that the magnetic dipole moments of the negative parity light mesons are smaller compared to those of the positive parity mesons. Contrary to the light meson case, magnetic dipole moments of the negative parity heavy mesons are larger than the ones for the positive parity mesons., 15 pages, 2 figures, LaTeX formatted

OBJECTIVE: To construct predictive models based on the objectively calculated risks of progression and recurrence of non-muscle-invasive bladder cancer (NMIBC) in a large cohort of patients from a single centre. PATIENTS AND METHODS: Between October 1984 and March 2009 a cohort of 1019 patients (877 males; 142 females; median age 44 years) with histologically confirmed NMIBC was included in this study. Among these patients, 74% received bacillus Calmette-Guérin (BCG)-based therapy. Complete transurethral resection of bladder tumour of all visible tumours was carried out in all patients, and the stage and grade were determined. Univariate analysis and multivariate Cox regression were used to identify predictors of recurrence and progression. The studied predictors included age, sex, stage, grade, associated carcinoma in situ, tumour size, multiplicity, macroscopic appearance of the tumour, history of recurrence and type of adjuvant intravesical therapy. Multivariate logistic regression models were used to develop the 12- and 60-month recurrence and progression predictive models. The predictive accuracy of the models was assessed for discrimination as well as calibration. RESULTS: The median (range) follow-up was 44 (6-254) months. On multivariate analysis, stage, multiplicity, history of recurrence and adjuvant intravesical therapy were significantly associated with recurrence, whereas for progression only tumour grade and size were significant independent predictors. The constructed nomograms had a 64.9% and 69.4% chance of correctly distinguishing between two patients, one destined to have a recurrence and one not at 12 and 60 months, respectively. The constructed nomograms had a 70.2% and 73.5% chance of correctly distinguishing between two patients, one destined to progress and one not at 12 and 60 months, respectively. All predictive models were well calibrated. CONCLUSIONS: Based on multivariate analysis of the studied prognostic factors nomograms for predicting recurrence and progression in NMIBC were constructed. Most of the studied patients had received BCG-based therapy, making these models more closely applicable to contemporary practice than others. These predictive models have reasonable discriminative ability and are well calibrated, but require external validation before they can be applied to other populations.

The effective potential of massless standard model (SM) is calculated up to three-loop order. The stability of the effective potential and the Higgs boson mass are investigated up to three-loop order. We found that, Higgs boson mass $m_{H}$ of one-loop order is large. The two-loop and three-loop results are not appreciably different from each other. The two-loop and three-loop radiative corrections have led to an improvement of Higgs boson mass and the value of the scalar coupling. For the value $m_{t}=170$ GeV at the energy scale $\mu\approx 5.68\times10^2$GeV, we get $m_{H2-loop}\approx 125.4$ GeV. At the energy scale $\mu\geq28\times10^2$, the scalar coupling $\lambda$ at two-loop becomes negative and leads to metastable vacuum while the three-loop level is stable even at high $\mu$ $\approx 10^{19}$ GeV. For the larger $\mu$-range $(3 \times 10^{3} \text{GeV}\leq \mu \leq 20 \times 10^{3} \text{GeV})$ spontaneous symmetry breaking for one-loop and three-loop occurs at approximately the same scalar coupling values. We get $m_{H1-loop}\approx 126.14$ GeV at $\mu \approx 6.5 \times 10^{3}$ GeV while for three-loop $m_{H3-loop}\approx 126$ GeV at $\mu \approx 20 \times 10^{3}$ GeV., Comment: 19 pages, 4 figures

The light cone sum rules method is used in studying the radiative decays $\Sigma_Q \to \Lambda_Q \gamma$ and $\Xi^\prime_Q \to \Xi_Q \gamma$. Firstly, the sum rules for the form factor $F_2(Q^2=0)$ responsible for these transitions is constructed. Using this result the decay widths of the above--mentioned decays are calculated and analyzed. A comparison of our predictions on the decay widths of considered transitions with the predictions of the other approaches is presented., Comment: 13 pages, no figures, LaTeX formatted

Micromechanical responses of granular materials are complex to understand when their behaviour is viewed in a single grain-scale. Experimental sensing of stresses within a grain-scale inside three dimensional particulate packing is still difficult to perform. In this work, photo stress analysis tomography (PSAT) is used to sense the fundamental nature of the stress experienced by different sizes of optically-sensitive inclusions inside granular packing (quasi-three dimensional) under an external axial-compression loading. The distribution of the maximum shear stress and the direction of the major principal stress experienced by the inclusions are analysed to understand the interplay between the size of the inclusions and their proximity to the wall boundary. The outcomes of this study provide a new understanding on the dual nature of stress transmission experienced by the inclusions, as a result of the combined size and wall effects. Relatively large inclusions experience dominantly shear stress close to the wall boundaries while this nature tends towards hydrostatic away from the wall boundaries. Smaller size inclusions could experience shear at both close to and away from wall boundaries of the granular assembly. Computer simulations using three-dimensional discrete element method (DEM) are also performed to compare the qualitative nature of stress experienced by inclusions inside particulate media. Qualitatively, the simulation results also agree with the experimental outcomes, that an increase in the relative size of the inclusion decreases its ability to experience shear. Using DEM simulations, the fabric structure of the inclusions is examined in depth under mechanical loading. An increase in the size of the inclusions tends to decrease the fabric anisotropy of the contacts and in particular the strong contacts, surrounding them. Hence the microscale origin of the weak mobilisation of shear in the large inclusions could be attributed to their relatively weak fabric anisotropy of the strong contacts surrounding them. These findings help to advance our understanding of the micromechanics of particulate systems, due to their size and proximity to wall boundaries: different sizes of the particles could sustain different nature of stresses within single-particle scale depending on their proximity to the wall boundaries.

The $\Sigma$--$\Lambda$ mixing angle is calculated in framework of the QCD sum rules. We find that our prediction for the mixing angle is $(1.00\pm 0.15)^0$ which is in good agreement with the quark model prediction, and approximately two times larger than the recent lattice QCD calculations., Comment: 5 pages, no figures, LaTeX formatted

International audience; no abstract

The perturbation technique within the framework of the asymptotic iteration method is used to obtain large-order shifted 1/N expansions, where N is the number of spatial dimensions. This method is contrary to the usual Rayleigh-Schr\"{o}dinger perturbation theory, no matrix elements need to be calculated. The method is applied to the Schr\"{o}dinger equation and the non-polynomial potential $V(r)=r^2+\frac{b r^2}{(1+cr^2)}$ in three dimensions is discussed as an illustrative example.