A physiological approach to renal clearance : from premature neonates to adults

Aims We propose using glomerular filtration rate (GFR) as the physiological basis for distinguishing components of renal clearance. Methods Gentamicin, amikacin and vancomycin are thought to be predominantly excreted by the kidneys. A mixed-effects joint model of the pharmacokinetics of these drugs was developed, with a wide dispersion of weight, age and serum creatinine. A dataset created from 18 sources resulted in 27,338 drug concentrations from 9,901 patients. Body size and composition, maturation and renal function were used to describe differences in drug clearance and volume of distribution. Results This study demonstrates that GFR is a predictor of two distinct components of renal elimination clearance: (1) GFR clearance associated with normal GFR and (2) non-GFR clearance not associated with normal GFR. All three drugs had GFR clearance estimated as a drug-specific percentage of normal GFR (gentamicin 39%, amikacin 90% and vancomycin 57%). The total clearance (sum of GFR and non-GFR clearance), standardized to 70 kg total body mass, 176 cm, male, renal function 1, was 5.58 L/h (95% confidence interval [CI] 5.50-5.69) (gentamicin), 7.77 L/h (95% CI 7.26-8.19) (amikacin) and 4.70 L/h (95% CI 4.61-4.80) (vancomycin). Conclusions GFR provides a physiological basis for renal drug elimination. It has been used to distinguish two elimination components. This physiological approach has been applied to describe clearance and volume of distribution from premature neonates to elderly adults with a wide dispersion of size, body composition and renal function. Dose individualization has been implemented using target concentration intervention

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

A physiological approach to renal clearance:From premature neonates to adults

Aims: We propose using glomerular filtration rate (GFR) as the physiological basis for distinguishing components of renal clearance. Methods: Gentamicin, amikacin and vancomycin are thought to be predominantly excreted by the kidneys. A mixed-effects joint model of the pharmacokinetics of these drugs was developed, with a wide dispersion of weight, age and serum creatinine. A dataset created from 18 sources resulted in 27,338 drug concentrations from 9,901 patients. Body size and composition, maturation and renal function were used to describe differences in drug clearance and volume of distribution. Results: This study demonstrates that GFR is a predictor of two distinct components of renal elimination clearance: (1) GFR clearance associated with normal GFR and (2) non-GFR clearance not associated with normal GFR. All three drugs had GFR clearance estimated as a drug-specific percentage of normal GFR (gentamicin 39%, amikacin 90% and vancomycin 57%). The total clearance (sum of GFR and non-GFR clearance), standardized to 70 kg total body mass, 176 cm, male, renal function 1, was 5.58 L/h (95% confidence interval [CI] 5.50-5.69) (gentamicin), 7.77 L/h (95% CI 7.26-8.19) (amikacin) and 4.70 L/h (95% CI 4.61-4.80) (vancomycin). Conclusions: GFR provides a physiological basis for renal drug elimination. It has been used to distinguish two elimination components. This physiological approach has been applied to describe clearance and volume of distribution from premature neonates to elderly adults with a wide dispersion of size, body composition and renal function. Dose individualization has been implemented using target concentration intervention.</p

Evidence of a J/ψΛJ/\psi\Lambda structure and observation of excited Ξ−\Xi^- states in the Ξb−→J/ψΛK−\Xi^-_b \to J/\psi\Lambda K^- decay

First evidence of a structure in the $J/\psi{\Lambda}$ invariant mass distribution is obtained from an amplitude analysis of $\Xi_b^-{\rightarrow}J/\psi{\Lambda}K^-$ decays. The observed structure is consistent with being due to a charmonium pentaquark with strangeness with a significance of $3.1\sigma$ including systematic uncertainties and look-elsewhere effect. Its mass and width are determined to be $4458.8\pm2.9^{+4.7}_{-1.1}$ MeV and $17.3\pm6.5^{+8.0}_{-5.7}$ MeV, respectively, where the quoted uncertainties are statistical and systematic. The structure is also consistent with being due to two resonances. In addition, the narrow excited $\Xi^-$ states, $\Xi(1690)^-$ and $\Xi(1820)^-$, are seen for the first time in a $\Xi^-_b$ decay, and their masses and widths are measured with improved precision. The analysis is performed using $pp$ collision data corresponding to a total integrated luminosity of 9 fb$^{-1}$, collected with the LHCb experiment at centre-of-mass energies of 7, 8 and 13 TeV

Observation of the Bs0 ⁣→D∗+D∗−B^0_s\!\to D^{*+}D^{*-} decay

International audienceThe first observation of the ${B}_s^0$→ D$^{∗+}$D$^{∗−}$ decay and the measurement of its branching ratio relative to the B$^{0}$→ D$^{∗+}$D$^{∗−}$ decay are presented. The data sample used corresponds to an integrated luminosity of 9 fb$^{−1}$ of proton-proton collisions recorded by the LHCb experiment at centre-of-mass energies of 7, 8 and 13 TeV between 2011 and 2018. The decay is observed with more than 10 standard deviations and the time-integrated ratio of branching fractions is determined to be$\frac{\mathcal{B}\left({B}_s^0\to {D}^{\ast +}{D}^{\ast -}\right)}{\mathcal{B}\left({B}^0\to {D}^{\ast +}{D}^{\ast -}\right)}=0.269\pm 0.032\pm 0.011\pm 0.008,$where the first uncertainty is statistical, the second systematic and the third due to the uncertainty of the fragmentation fraction ratio f$_{s}$/f$_{d}$. The ${B}_s^0$→ D$^{*+}$D$^{*−}$ branching fraction is calculated to be$\mathcal{B}\left({B}_s^0\to {D}^{\ast +}{D}^{\ast -}\right)=\left(2.15\pm 0.26\pm 0.09\pm 0.06\pm 0.16\right)\times {10}^{-4},$where the fourth uncertainty is due to the B$^{0}$→ D$^{*+}$D$^{*−}$ branching fraction. These results are calculated using the average ${B}_s^0$ meson lifetime in simulation. Correction factors are reported for scenarios where either a purely heavy or a purely light ${B}_s^0$ eigenstate is considered.[graphic not available: see fulltext

Measurement of the CKM angle γγ with B±→D[K∓π±π±π∓]h± B^\pm \to D[K^\mp π^\pm π^\pm π^\mp] h^\pm decays using a binned phase-space approach

The CKM angle $\gamma$ is determined from $C\!P$-violating observables measured in ${B^\pm \to D[ K^\mp \pi^\pm\pi^\pm\pi^\mp] h^\pm}$, $(h = K,\pi)$ decays, where the measurements are performed in bins of the decay phase-space of the $D$ meson. Using proton-proton collision data collected by the LHCb experiment at centre-of-mass energies of $7, 8$ and $13\,\text{TeV}$, corresponding to a total integrated luminosity of $9\,\text{fb}^{-1}$, $\gamma$ is determined to be \begin{equation*} \gamma = \left( 54.8 \: ^{+\:6.0 }_{-\:5.8} \: ^{+\:0.6}_{-\:0.6} \: ^{+\:6.7}_{-\:4.3} \right)^\circ, \end{equation*} where the first uncertainty is statistical, the second systematic and the third from the external inputs on the coherence factors and strong phases of the $D$-meson decays.The CKM angle γ is determined from CP-violating observables measured in B$^{±}$ → D[K$^{∓}$π$^{±}$π$^{±}$π$^{∓}$]h$^{±}$, (h = K, π) decays, where the measurements are performed in bins of the decay phase-space of the D meson. Using proton-proton collision data collected by the LHCb experiment at centre-of-mass energies of 7, 8 and 13 TeV, corresponding to a total integrated luminosity of 9 fb$^{−1}$, γ is determined to be$\gamma ={\left(54.8\begin{array}{c}+6.0\\ {}-5.8\end{array}\begin{array}{c}+0.6\\ {}-0.6\end{array}\begin{array}{c}+6.7\\ {}-4.3\end{array}\right)}^{\circ },$where the first uncertainty is statistical, the second systematic and the third from the external inputs on the coherence factors and strong phases of the D-meson decays.[graphic not available: see fulltext]The CKM angle $\gamma$ is determined from $C\!P$-violating observables measured in ${B^\pm \to D[ K^\mp \pi^\pm\pi^\pm\pi^\mp] h^\pm}$, $(h = K,\pi)$ decays, where the measurements are performed in bins of the decay phase-space of the $D$ meson. Using proton-proton collision data collected by the LHCb experiment at centre-of-mass energies of $7, 8$ and $13\,\text{TeV}$, corresponding to a total integrated luminosity of $9\,\text{fb}^{-1}$, $\gamma$ is determined to be \begin{equation*} \gamma = \left( 54.8 \: ^{+\:6.0 }_{-\:5.8} \: ^{+\:0.6}_{-\:0.6} \: ^{+\:6.7}_{-\:4.3} \right)^\circ, \end{equation*} where the first uncertainty is statistical, the second systematic and the third from the external inputs on the coherence factors and strong phases of the $D$-meson decays

Search for the baryon- and lepton-number violating decays B0→pμ−B^0\to p\mu^- and Bs0→pμ−B^0_s\to p\mu^-

A search for the baryon- and lepton-number violating decays $B^0\to p\mu^-$ and $B^0_s\to p\mu^-$ is performed at the LHCb experiment using data collected in proton-proton collisions at $\sqrt{s}$ = 7, 8 and 13 TeV, corresponding to integrated luminosities of 1, 2 and 6 fb$^{-1}$, respectively. No significant signal for $B^0\to p\mu^-$ and $B^0_s\to p\mu^-$ decays is found and the upper limits on the branching fractions are determined to be {\cal B}(B^0\to p\mu^-)B0→pμ- and Bs0→pμ- is performed at the LHCb experiment using data collected in proton-proton collisions at s=7, 8 and 13 TeV, corresponding to integrated luminosities of 1, 2, and 6  fb-1, respectively. No significant signal for B0→pμ- and Bs0→pμ- decays is found and the upper limits on the branching fractions are determined to be B(B0→pμ-)<2.6(3.1)×10-9 and B(Bs0→pμ-)<12.1(14.0)×10-9, respectively, at 90% (95%) confidence level. These are the first limits on these decays to date.A search for the baryon- and lepton-number violating decays B^0\to p\mu^-$and$B^0_s\to p\mu^-$is performed at the LHCb experiment using data collected in proton-proton collisions at$\sqrt{s}$= 7, 8 and 13 TeV, corresponding to integrated luminosities of 1, 2 and 6 fb$^{-1}$, respectively. No significant signal for$B^0\to p\mu^-$and$B^0_s\to p\mu^-$decays is found and the upper limits on the branching fractions are determined to be${\cal B}(B^0\to p\mu^-)<2.6\,(3.1)\times10^{-9}$and${\cal B}(B^0_s\to p\mu^-)<12.1\,(14.0)\times10^{-9}$, respectively, at 90$\%$(95$\%$) confidence level. These are the first limits on these decays to date