A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Survival of 86,690 patients with thyroid cancer: A population-based study in 29 European countries from EUROCARE-5

Background Incidence rates of thyroid cancer (TC) increased in several countries during the last 30 years, while mortality rates remained unchanged, raising important questions for treatment and follow-up of TC patients. This study updates population-based estimates of relative survival (RS) after TC diagnosis in Europe by sex, country, age, period and histology. Methods Data from 87 cancer registries in 29 countries were extracted from the EUROCARE-5 dataset. One- and 5-year RS were estimated using the cohort approach for 86,690 adult TC patients diagnosed in 2000â\u80\u932007 and followed-up to 12/31/2008. RS trends in 1999â\u80\u932007 and 10-year RS in 2005â\u80\u932007 were estimated using the period approach. Results In Europe 2000â\u80\u932007, 5-year RS after TC was 88% in women and 81% in men. Survival rates varied by country and were strongly correlated (Pearson Ï\u81 = 75%) with country-specific incidence rates. Five-year RS decreased with age (in women from >95% at age 15â\u80\u9354 to 57% at age 75+), from 98% in women and 94% in men with papillary TC to 14% in women and 12% in men with anaplastic TC. Proportion of papillary TC varied by country and increased over time, while survival rates were similar across areas and periods. In 1999â\u80\u932007, 5-year RS increased by five percentage points for all TCs but only by two for papillary and by four for follicular TC. Ten-year RS in 2005â\u80\u932007 was 89% in women and 79% in men. Conclusions The reported increasing TC survival trend and differences by area are mainly explained by the varying histological case-mix of cases

Measurement of the Cross Sections of Ξc0\Xi^0_{c} and Ξc+\Xi^+_{c} Baryons and of the Branching-Fraction Ratio BR(Ξc0→Ξ−e+νe\Xi^0_{c} \rightarrow \Xi^-{e}^+\nu_{ e})/BR(Ξc0→Ξ−π+\Xi^0_{c} \rightarrow \Xi^-\pi^+) in pp collisions at 13 TeV

The $p_T$-differential cross sections of prompt charm-strange baryons Ξ$_c^0$ and Ξ$_c^+$ were measured at midrapidity (|y|<0.5) in proton-proton (pp) collisions at a center-of-mass energy $\sqrt{s}$ = 13 TeV with the ALICE detector at the LHC. The Ξ$_c^0$ baryon was reconstructed via both the semileptonic decay (Ξ$^-$e$^+$ν$_e$) and the hadronic decay (Ξ$^-$π$^+$) channels. The Ξ$_c^+$ baryon was reconstructed via the hadronic decay (Ξ$^-$π$^+$π$^+$) channel. The branching-fraction ratio BR(Ξ$_c^0$→Ξ$^-$e$^+$ν$_e$)/BR(Ξ$_c^0$→Ξ$^-$π$^+$) = 1.38±0.14(stat)±0.22(syst) was measured with a total uncertainty reduced by a factor of about 3 with respect to the current world average reported by the Particle Data Group. The transverse momentum ($p_T$) dependence of the Ξ$_c^0-$ and Ξ$_c^+$-baryon production relative to the D$^0$ meson and to the Σ$_c^{0,+,++}$- and Λ$_c^+$-baryon production are reported. The baryon-to-meson ratio increases toward low $p_T$ up to a value of approximately 0.3. The measurements are compared with various models that take different hadronization mechanisms into consideration. The results provide stringent constraints to these theoretical calculations and additional evidence that different processes are involved in charm hadronization in electron-positron (e$^+$e$^-$) and hadronic collisions

Multiharmonic Correlations of Different Flow Amplitudes in Pb-Pb Collisions at sNN=2.76\sqrt{s_{_{NN}}}=2.76 TeV

The event-by-event correlations between three flow amplitudes are measured for the first time in Pb-Pb collisions, using higher-order symmetric cumulants. We find that different three-harmonic correlations develop during the collective evolution of the medium when compared to correlations that exist in the initial state. These new results cannot be interpreted in terms of previous lower-order flow measurements since contributions from two-harmonic correlations are explicitly removed in the new observables. A comparison to Monte Carlo simulations provides new and independent constraints for the initial conditions and system properties of nuclear matter created in heavy-ion collisions

Pseudorapidity distributions of charged particles as a function of mid- and forward rapidity multiplicities in pp collisions at s\sqrt{s} = 5.02, 7 and 13 TeV

The multiplicity dependence of the pseudorapidity density of charged particles in proton–proton (pp) collisions at centre-of-mass energies $\sqrt{s}~=~5.02$, 7 and 13 TeV measured by ALICE is reported. The analysis relies on track segments measured in the midrapidity range ($|\eta | < 1.5$). Results are presented for inelastic events having at least one charged particle produced in the pseudorapidity interval $|\eta |<1$. The multiplicity dependence of the pseudorapidity density of charged particles is measured with mid- and forward rapidity multiplicity estimators, the latter being less affected by autocorrelations. A detailed comparison with predictions from the PYTHIA 8 and EPOS LHC event generators is also presented. The results can be used to constrain models for particle production as a function of multiplicity in pp collisions

Measurement of the low-energy antideuteron inelastic cross section

In this Letter, we report the first measurement of the inelastic cross section for antideuteron-nucleus interactions at low particle momenta, covering a range of 0.3 ≤ p < 4 GeV/c. The measurement is carried out using p-Pb collisions at a center-of-mass energy per nucleon–nucleon pair of $\sqrt{s_{\rm NN}}$ = 5.02 TeV, recorded with the ALICE detector at the CERN LHC and utilizing the detector material as an absorber for antideuterons and antiprotons. The extracted raw primary antiparticle-to-particle ratios are compared to the results from detailed ALICE simulations based on the geant4 toolkit for the propagation of (anti)particles through the detector material. The analysis of the raw primary (anti)proton spectra serves as a benchmark for this study, since their hadronic interaction cross sections are well constrained experimentally. The first measurement of the inelastic cross section for antideuteron-nucleus interactions averaged over the ALICE detector material with atomic mass numbers ⟨A⟩ = 17.4 and 31.8 is obtained. The measured inelastic cross section points to a possible excess with respect to the Glauber model parametrization used in geant4 in the lowest momentum interval of 0.3 ≤ p < 0.47 GeV/c up to a factor 2.1. This result is relevant for the understanding of antimatter propagation and the contributions to antinuclei production from cosmic ray interactions within the interstellar medium. In addition, the momentum range covered by this measurement is of particular importance to evaluate signal predictions for indirect dark-matter searches

Jet fragmentation transverse momentum distributions in pp and p-Pb collisions at s \sqrt{s} , sNN \sqrt{s_{\mathrm{NN}}} = 5.02 TeV

Jet fragmentation transverse momentum (j$_{T}$) distributions are measured in proton-proton (pp) and proton-lead (p-Pb) collisions at $\sqrt{s_{\mathrm{NN}}}$ = 5.02 TeV with the ALICE experiment at the LHC. Jets are reconstructed with the ALICE tracking detectors and electromagnetic calorimeter using the anti-k$_{T}$ algorithm with resolution parameter R = 0.4 in the pseudorapidity range |η| < 0.25. The j$_{T}$ values are calculated for charged particles inside a fixed cone with a radius R = 0.4 around the reconstructed jet axis. The measured j$_{T}$ distributions are compared with a variety of parton-shower models. Herwig and Pythia 8 based models describe the data well for the higher j$_{T}$ region, while they underestimate the lower j$_{T}$ region. The j$_{T}$ distributions are further characterised by fitting them with a function composed of an inverse gamma function for higher j$_{T}$ values (called the “wide component”), related to the perturbative component of the fragmentation process, and with a Gaussian for lower j$_{T}$ values (called the “narrow component”), predominantly connected to the hadronisation process. The width of the Gaussian has only a weak dependence on jet transverse momentum, while that of the inverse gamma function increases with increasing jet transverse momentum. For the narrow component, the measured trends are successfully described by all models except for Herwig. For the wide component, Herwig and PYTHIA 8 based models slightly underestimate the data for the higher jet transverse momentum region. These measurements set constraints on models of jet fragmentation and hadronisation

Measurements of the groomed and ungroomed jet angularities in pp collisions at s \sqrt{s} = 5.02 TeV

International audienceThe jet angularities are a class of jet substructure observables which characterize the angular and momentum distribution of particles within jets. These observables are sensitive to momentum scales ranging from perturbative hard scatterings to nonperturbative fragmentation into final-state hadrons. We report measurements of several groomed and ungroomed jet angularities in pp collisions at $\sqrt{s}$ = 5.02 TeV with the ALICE detector. Jets are reconstructed using charged particle tracks at midrapidity (|η| < 0.9). The anti-k$_{T}$ algorithm is used with jet resolution parameters R = 0.2 and R = 0.4 for several transverse momentum {p}_{\mathrm{T}}^{\mathrm{ch}} ^{jet} intervals in the 20–100 GeV/c range. Using the jet grooming algorithm Soft Drop, the sensitivity to softer, wide-angle processes, as well as the underlying event, can be reduced in a way which is well-controlled in theoretical calculations. We report the ungroomed jet angularities, λ$_{α}$, and groomed jet angularities, λ$_{α,g}$, to investigate the interplay between perturbative and nonperturbative effects at low jet momenta. Various angular exponent parameters α = 1, 1.5, 2, and 3 are used to systematically vary the sensitivity of the observable to collinear and soft radiation. Results are compared to analytical predictions at next-to-leading-logarithmic accuracy, which provide a generally good description of the data in the perturbative regime but exhibit discrepancies in the nonperturbative regime. Moreover, these measurements serve as a baseline for future ones in heavy-ion collisions by providing new insight into the interplay between perturbative and nonperturbative effects in the angular and momentum substructure of jets. They supply crucial guidance on the selection of jet resolution parameter, jet transverse momentum, and angular scaling variable for jet quenching studies.[graphic not available: see fulltext

Experimental Evidence for an Attractive p-ϕ\phi Interaction

This Letter presents the first experimental evidence of the attractive strong interaction between a proton and a ϕ meson. The result is obtained from two-particle correlations of combined $p$-ϕ⊕ $\bar{p}$-ϕ pairs measured in high-multiplicity pp collisions at $\sqrt{s}$ = 13 TeV by the ALICE Collaboration. The spin-averaged scattering length and effective range of the p-ϕ interaction are extracted from the fully corrected correlation function employing the Lednický-Lyuboshits approach. In particular, the imaginary part of the scattering length vanishes within uncertainties, indicating that inelastic processes do not play a prominent role for the p-ϕ interaction. These data demonstrate that the interaction is dominated by elastic p-ϕ scattering. Furthermore, an analysis employing phenomenological Gaussian- and Yukawa-type potentials is conducted. Under the assumption of the latter, the N-ϕ coupling constant is found to be $g_{N-ϕ}$ = 0.14 ± 0.03(stat) ± 0.02(syst). This work provides valuable experimental input to accomplish a self-consistent description of the N-ϕ interaction, which is particularly relevant for the more fundamental studies on partial restoration of chiral symmetry in nuclear medium

Kaon–proton strong interaction at low relative momentum via femtoscopy in Pb–Pb collisions at the LHC

In quantum scattering processes between two particles, aspects characterizing the strong and Coulomb forces can be observed in kinematic distributions of the particle pairs. The sensitivity to the interaction potential reaches a maximum at low relative momentum and vanishing distance between the two particles. Ultrarelativistic heavy-ion collisions at the LHC provide an abundant source of many hadron species and can be employed as a measurement method of scattering parameters that is complementary to scattering experiments. This study confirms that momentum correlations of particles produced in Pb–Pb collisions at the LHC provide an accurate measurement of kaon–proton scattering parameters at low relative momentum, allowing precise access to the $K^- p \to K^- p$ process. This work also validates the femtoscopic measurement in ultrarelativistic heavy-ion collisions as an alternative to scattering experiments and a complementary tool to the study of exotic atoms with comparable precision. In this work, the first femtoscopic measurement of momentum correlations of $K^- p(K^- \overline{p})$ and $K^+p(K^-\overline{p})$ pairs in Pb–Pb collisions at centre-of-mass energy per nucleon pair of $\sqrt{s_{NN}}$=5.02 TeV registered by the ALICE experiment is reported. The components of the $K^-p$ complex scattering length are extracted and found to be $\Re f_0=-0.91 \pm 0.03 \textrm{(stat)}^{+0.17}_{-0.03} \textrm{(syst)}$ and $\Im f_0=0.92 \pm 0.05 \textrm{(stat)}_{-0.33}^{+0.12} \textrm{(syst)}$. The results are compared with chiral effective field theory predictions as well as with existing data from dedicated scattering and exotic kaonic atom experiments