Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10(-5)). For three cis-eQTL associations (P<1.4 × 10(-3), FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P=6 × 10(-10) for risk variants (P<10(-4)) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC.
Wildlife must adapt to human presence to survive in the Anthropocene, so it is critical to understand species responses to humans in different contexts. We used camera trapping as a lens to view mammal responses to changes in human activity during the COVID-19 pandemic. Across 163 species sampled in 102 projects around the world, changes in the amount and timing of animal activity varied widely. Under higher human activity, mammals were less active in undeveloped areas but unexpectedly more active in developed areas while exhibiting greater nocturnality. Carnivores were most sensitive, showing the strongest decreases in activity and greatest increases in nocturnality. Wildlife managers must consider how habituation and uneven sensitivity across species may cause fundamental differences in human-wildlife interactions along gradients of human influence.
Science is crucial for evidence-based decision-making. Public trust in scientists can help decision makers act on the basis of the best available evidence, especially during crises. However, in recent years the epistemic authority of science has been challenged, causing concerns about low public trust in scientists. We interrogated these concerns with a preregistered 68-country survey of 71,922 respondents and found that in most countries, most people trust scientists and agree that scientists should engage more in society and policymaking. We found variations between and within countries, which we explain with individual- and country-level variables, including political orientation. While there is no widespread lack of trust in scientists, we cannot discount the concern that lack of trust in scientists by even a small minority may affect considerations of scientific evidence in policymaking. These findings have implications for scientists and policymakers seeking to maintain and increase trust in scientists.
Science is integral to society because it can inform individual, government, corporate, and civil society decision-making on issues such as public health, new technologies or climate change. Yet, public distrust and populist sentiment challenge the relationship between science and society. To help researchers analyse the science-society nexus across different geographical and cultural contexts, we undertook a cross-sectional population survey resulting in a dataset of 71,922 participants in 68 countries. The data were collected between November 2022 and August 2023 as part of the global Many Labs study "Trust in Science and Science-Related Populism" (TISP). The questionnaire contained comprehensive measures for individuals' trust in scientists, science-related populist attitudes, perceptions of the role of science in society, science media use and communication behaviour, attitudes to climate change and support for environmental policies, personality traits, political and religious views and demographic characteristics. Here, we describe the dataset, survey materials and psychometric properties of key variables. We encourage researchers to use this unique dataset for global comparative analyses on public perceptions of science and its role in society and policy-making.
We present first evidence that the cosine of the CP-violating weak phase 2β is positive, and hence exclude trigonometric multifold solutions of the Cabibbo-Kobayashi-Maskawa (CKM) Unitarity Triangle using a time-dependent Dalitz plot analysis of B^{0}→D^{(*)}h^{0} with D→K_{S}^{0}π^{+}π^{-} decays, where h^{0}∈{π^{0},η,ω} denotes a light unflavored and neutral hadron. The measurement is performed combining the final data sets of the BABAR and Belle experiments collected at the ϒ(4S) resonance at the asymmetric-energy B factories PEP-II at SLAC and KEKB at KEK, respectively. The data samples contain (471±3)×10^{6}BB[over ¯] pairs recorded by the BABAR detector and (772±11)×10^{6}BB[over ¯] pairs recorded by the Belle detector. The results of the measurement are sin2β=0.80±0.14(stat)±0.06(syst)±0.03(model) and cos2β=0.91±0.22(stat)±0.09(syst)±0.07(model). The result for the direct measurement of the angle β of the CKM Unitarity Triangle is β=[22.5±4.4(stat)±1.2(syst)±0.6(model)]°. The measurement assumes no direct CP violation in B^{0}→D^{(*)}h^{0} decays. The quoted model uncertainties are due to the composition of the D^{0}→K_{S}^{0}π^{+}π^{-} decay amplitude model, which is newly established by performing a Dalitz plot amplitude analysis using a high-statistics e^{+}e^{-}→cc[over ¯] data sample. CP violation is observed in B^{0}→D^{(*)}h^{0} decays at the level of 5.1 standard deviations. The significance for cos2β>0 is 3.7 standard deviations. The trigonometric multifold solution π/2-β=(68.1±0.7)° is excluded at the level of 7.3 standard deviations. The measurement resolves an ambiguity in the determination of the apex of the CKM Unitarity Triangle.
Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.
To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.
Searches are presented for direct production of top or bottom squark pairs in proton-proton collisions at the CERN LHC. Two searches, based on complementary techniques, are performed in all-jet final states that are characterized by a significant imbalance in transverse momentum. An additional search requires the presence of a charged lepton isolated from other activity in the event. The data were collected in 2015 at a centre-of-mass energy of 13[Formula: see text] with the CMS detector and correspond to an integrated luminosity of 2.3[Formula: see text]. No statistically significant excess of events is found beyond the expected contribution from standard model processes. Exclusion limits are set in the context of simplified models of top or bottom squark pair production. Models with top and bottom squark masses up to 830 and 890[Formula: see text], respectively, are probed for light neutralinos. For models with top squark masses of 675[Formula: see text], neutralino masses up to 260[Formula: see text] are excluded at 95% confidence level.
The production of jets in association with Z bosons, reconstructed via the μ^{+}μ^{-} and e^{+}e^{-} decay channels, is studied in pp and, for the first time, in Pb-Pb collisions. Both data samples were collected by the CMS experiment at the LHC, at a nucleon-nucleon center-of-mass energy of 5.02 TeV. The Pb-Pb collisions were analyzed in the 0%-30% centrality range. The back-to-back azimuthal alignment was studied in both pp and Pb-Pb collisions for Z bosons with transverse momentum p_{T}^{Z}>60 GeV/c and a recoiling jet with p_{T}^{jet}>30 GeV/c. The p_{T} imbalance x_{jZ}=p_{T}^{jet}/p_{T}^{Z}, as well as the average number of jet partners per Z, R_{jZ}, was studied in intervals of p_{T}^{Z}. The R_{jZ} is found to be smaller in Pb-Pb than in pp collisions, which suggests that in Pb-Pb collisions a larger fraction of partons associated with the Z bosons fall below the 30 GeV/c p_{T}^{jet} threshold because they lose energy.
Normalized double-differential cross sections for top quark pair ([Formula: see text]) production are measured in pp collisions at a centre-of-mass energy of 8[Formula: see text] with the CMS experiment at the LHC. The analyzed data correspond to an integrated luminosity of 19.7[Formula: see text]. The measurement is performed in the dilepton [Formula: see text] final state. The [Formula: see text] cross section is determined as a function of various pairs of observables characterizing the kinematics of the top quark and [Formula: see text] system. The data are compared to calculations using perturbative quantum chromodynamics at next-to-leading and approximate next-to-next-to-leading orders. They are also compared to predictions of Monte Carlo event generators that complement fixed-order computations with parton showers, hadronization, and multiple-parton interactions. Overall agreement is observed with the predictions, which is improved when the latest global sets of proton parton distribution functions are used. The inclusion of the measured [Formula: see text] cross sections in a fit of parametrized parton distribution functions is shown to have significant impact on the gluon distribution.
The first measurement of the jet mass [Formula: see text] of top quark jets produced in [Formula: see text] events from pp collisions at [Formula: see text] [Formula: see text] is reported for the jet with the largest transverse momentum [Formula: see text] in highly boosted hadronic top quark decays. The data sample, collected with the CMS detector, corresponds to an integrated luminosity of 19.7[Formula: see text]. The measurement is performed in the lepton+jets channel in which the products of the semileptonic decay [Formula: see text] with [Formula: see text] where [Formula: see text] is an electron or muon, are used to select [Formula: see text] events with large Lorentz boosts. The products of the fully hadronic decay [Formula: see text] with [Formula: see text] are reconstructed using a single Cambridge-Aachen jet with distance parameter [Formula: see text], and [Formula: see text] [Formula: see text]. The [Formula: see text] cross section as a function of [Formula: see text] is unfolded at the particle level and is used to test the modelling of highly boosted top quark production. The peak position of the [Formula: see text] distribution is sensitive to the top quark mass [Formula: see text], and the data are used to extract a value of [Formula: see text] to assess this sensitivity.
A measurement of the top quark mass is reported in events containing a single top quark produced via the electroweak t channel. The analysis is performed using data from proton-proton collisions collected with the CMS detector at the LHC at a centre-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 19.7 fb[Formula: see text]. Top quark candidates are reconstructed from their decay to a [Formula: see text] boson and a b quark, with the [Formula: see text] boson decaying leptonically to a muon and a neutrino. The final state signature and kinematic properties of single top quark events in the t channel are used to enhance the purity of the sample, suppressing the contribution from top quark pair production. A fit to the invariant mass distribution of reconstructed top quark candidates yields a value of the top quark mass of [Formula: see text]. This result is in agreement with the current world average, and represents the first measurement of the top quark mass in event topologies not dominated by top quark pair production, therefore contributing to future averages with partially uncorrelated systematic uncertainties and a largely uncorrelated statistical uncertainty.
A search is reported for a narrow vector resonance decaying to quark-antiquark pairs in proton-proton collisions at sqrt[s]=13 TeV, collected with the CMS detector at the LHC. The data sample corresponds to an integrated luminosity of 2.7 fb^{-1}. The vector resonance is produced at large transverse momenta, with its decay products merged into a single jet. The resulting signature is a peak over background in the distribution of the invariant mass of the jet. The results are interpreted in the framework of a leptophobic vector resonance and no evidence is found for such particles in the mass range of 100-300 GeV. Upper limits at 95% confidence level on the production cross section are presented in a region of mass-coupling phase space previously unexplored at the LHC. The region below 140 GeV has not been explored by any previous experiments.
Results are reported from a search for supersymmetric particles in proton-proton collisions in the final state with a single lepton, multiple jets, including at least one b-tagged jet, and large missing transverse momentum. The search uses a sample of proton-proton collision data at sqrt[s]=13 TeV recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 35.9 fb^{-1}. The observed event yields in the signal regions are consistent with those expected from standard model backgrounds. The results are interpreted in the context of simplified models of supersymmetry involving gluino pair production, with gluino decay into either on- or off-mass-shell top squarks. Assuming that the top squarks decay into a top quark plus a stable, weakly interacting neutralino, scenarios with gluino masses up to about 1.9 TeV are excluded at 95% confidence level for neutralino masses up to about 1 TeV.
The differential production cross sections of B^{±} mesons are measured via the exclusive decay channels B^{±}→J/ψK^{±}→μ^{+}μ^{-}K^{±} as a function of transverse momentum in pp and Pb-Pb collisions at a center-of-mass energy sqrt[s_{NN}]=5.02 TeV per nucleon pair with the CMS detector at the LHC. The pp(Pb-Pb) data set used for this analysis corresponds to an integrated luminosity of 28.0 pb^{-1} (351 μb^{-1}). The measurement is performed in the B^{±} meson transverse momentum range of 7 to 50 GeV/c, in the rapidity interval |y|<2.4. In this kinematic range, a strong suppression of the production cross section by about a factor of 2 is observed in the Pb-Pb system in comparison to the expectation from pp reference data. These results are found to be roughly compatible with theoretical calculations incorporating beauty quark diffusion and energy loss in a quark-gluon plasma.
A search for new phenomena is performed in final states containing one or more jets and an imbalance in transverse momentum in pp collisions at a centre-of-mass energy of 13[Formula: see text]. The analysed data sample, recorded with the CMS detector at the CERN LHC, corresponds to an integrated luminosity of 2.3[Formula: see text]. Several kinematic variables are employed to suppress the dominant background, multijet production, as well as to discriminate between other standard model and new physics processes. The search provides sensitivity to a broad range of new-physics models that yield a stable weakly interacting massive particle. The number of observed candidate events is found to agree with the expected contributions from standard model processes, and the result is interpreted in the mass parameter space of fourteen simplified supersymmetric models that assume the pair production of gluinos or squarks and a range of decay modes. For models that assume gluino pair production, masses up to 1575 and 975[Formula: see text] are excluded for gluinos and neutralinos, respectively. For models involving the pair production of top squarks and compressed mass spectra, top squark masses up to 400[Formula: see text] are excluded.
A search for charged Higgs bosons produced via vector boson fusion and decaying into W and Z bosons using proton-proton collisions at sqrt[s]=13 TeV is presented. The data sample corresponds to an integrated luminosity of 15.2 fb^{-1} collected with the CMS detector in 2015 and 2016. The event selection requires three leptons (electrons or muons), two jets with large pseudorapidity separation and high dijet mass, and missing transverse momentum. The observation agrees with the standard model prediction. Limits on the vector boson fusion production cross section times branching fraction for new charged physical states are reported as a function of mass from 200 to 2000 GeV and interpreted in the context of Higgs triplet models.
An inclusive search for the standard model Higgs boson (H) produced with large transverse momentum (p_{T}) and decaying to a bottom quark-antiquark pair (bb[over ¯]) is performed using a data set of pp collisions at sqrt[s]=13 TeV collected with the CMS experiment at the LHC. The data sample corresponds to an integrated luminosity of 35.9 fb^{-1}. A highly Lorentz-boosted Higgs boson decaying to bb[over ¯] is reconstructed as a single, large radius jet, and it is identified using jet substructure and dedicated b tagging techniques. The method is validated with Z→bb[over ¯] decays. The Z→bb[over ¯] process is observed for the first time in the single-jet topology with a local significance of 5.1 standard deviations (5.8 expected). For a Higgs boson mass of 125 GeV, an excess of events above the expected background is observed (expected) with a local significance of 1.5 (0.7) standard deviations. The measured cross section times branching fraction for production via gluon fusion of H→bb[over ¯] with reconstructed p_{T}>450 GeV and in the pseudorapidity range -2.5