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Non-standard errors
(2021)
In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in sample estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: non-standard errors. To study them, we let 164 teams test six hypotheses on the same sample. We find that non-standard errors are sizeable, on par with standard errors. Their size (i) co-varies only weakly with team merits, reproducibility, or peer rating, (ii) declines significantly after peer-feedback, and (iii) is underestimated by participants.
Additive manufacturing or 3D printing as an umbrella term for various materials processing methods has distinct advantages over many other processing methods, including the ability to generate highly complex shapes and designs. However, the performance of any produced part not only depends on the material used and its shape, but is also critically dependent on its surface properties. Important features, such as wetting or fouling, critically depend mainly on the immediate surface energy. To gain control over the surface chemistry post-processing modifications are generally necessary, since it′s not a feature of additive manufacturing. Here, we report on the use of initiator and catalyst-free photografting and photopolymerization for the hydrophilic modification of microfiber scaffolds obtained from hydrophobic medical-grade poly(ε-caprolactone) via melt-electrowriting. Contact angle measurements and Raman spectroscopy confirms the formation of a more hydrophilic coating of poly(2-hydroxyethyl methacrylate). Apart from surface modification, we also observe bulk polymerization, which is expected for this method, and currently limits the controllability of this procedure.
Accurate determination of the evolutionary relationships between genes is a foundational challenge in biology. Homology—evolutionary relatedness—is in many cases readily determined based on sequence similarity analysis. By contrast, whether or not two genes directly descended from a common ancestor by a speciation event (orthologs) or duplication event (paralogs) is more challenging, yet provides critical information on the history of a gene. Since 2009, this task has been the focus of the Quest for Orthologs (QFO) Consortium. The sixth QFO meeting took place in Okazaki, Japan in conjunction with the 67th National Institute for Basic Biology conference. Here, we report recent advances, applications, and oncoming challenges that were discussed during the conference. Steady progress has been made toward standardization and scalability of new and existing tools. A feature of the conference was the presentation of a panel of accessible tools for phylogenetic profiling and several developments to bring orthology beyond the gene unit—from domains to networks. This meeting brought into light several challenges to come: leveraging orthology computations to get the most of the incoming avalanche of genomic data, integrating orthology from domain to biological network levels, building better gene models, and adapting orthology approaches to the broad evolutionary and genomic diversity recognized in different forms of life and viruses.
HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
(2021)
Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.
Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed.
We report first results on elliptic flow of identified particles at midrapidity in Au+Au collisions at sqrt[sNN] = 130 GeV using the STAR TPC at RHIC. The elliptic flow as a function of transverse momentum and centrality differs significantly for particles of different masses. This dependence can be accounted for in hydrodynamic models, indicating that the system created shows a behavior consistent with collective hydrodynamical flow. The fit to the data with a simple model gives information on the temperature and flow velocities at freeze-out.
The production of J/ψ is measured at midrapidity (|y|<0.9) in proton-proton collisions at s√ = 5.02 and 13 TeV, through the dielectron decay channel, using the ALICE detector at the Large Hadron Collider. The data sets used for the analyses correspond to integrated luminosities of Lint = 19.4 ± 0.4 nb−1 and Lint = 32.2 ± 0.5 nb−1 at s√ = 5.02 and 13 TeV, respectively. The fraction of non-prompt J/ψ mesons, i.e. those originating from the decay of beauty hadrons, is measured down to a transverse momentum pT = 2 GeV/c (1 GeV/c) at s√ = 5.02 TeV (13 TeV). The pT and rapidity (y) differential cross sections, as well as the corresponding values integrated over pT and y, are carried out separately for prompt and non-prompt J/ψ mesons. The results are compared with measurements from other experiments and theoretical calculations based on quantum chromodynamics (QCD). The shape of the pT and y distributions of beauty quarks predicted by state-of-the-art perturbative QCD models are used to extrapolate the bb¯¯¯ pair cross section at midrapidity and in the total phase space. The total bb¯¯¯ cross sections are found to be σbb¯¯¯=502±16(stat.)±51(syst.)+2−3(extr.) μb and σbb¯¯¯=218±37(stat.)±32(syst.)+8.2−9.1(extr.)μb at s√ = 13 and 5.02 TeV, respectively. The value at s√ = 13 TeV is obtained from the combination of ALICE and LHCb measurements.
Measurements of elliptic (v2) and triangular (v3) flow coefficients of π±, K±, p+p¯¯¯, K0S, and Λ+Λ¯¯¯¯ obtained with the scalar product method in Xe-Xe collisions at sNN−−−√ = 5.44 TeV are presented. The results are obtained in the rapidity range |y| < 0.5 and reported as a function of transverse momentum, pT, for several collision centrality classes. The flow coefficients exhibit a particle mass dependence for pT < 3 GeV/c, while a grouping according to particle type (i.e., meson and baryon) is found at intermediate transverse momenta (3 < pT < 8 GeV/c). The magnitude of the baryon v2 is larger than that of mesons up to pT = 6 GeV/c. The centrality dependence of the shape evolution of the pT-differential v2 is studied for the various hadron species. The v2 coefficients of π±, K±, and p+p¯¯¯ are reproduced by MUSIC hydrodynamic calculations coupled to a hadronic cascade model (UrQMD) for pT < 1 GeV/c. A comparison with vn measurements in the corresponding centrality intervals in Pb-Pb collisions at sNN−−−√ = 5.02 TeV yields an enhanced v2 in central collisions and diminished value in semicentral collisions.
Two-particle Azimuthal correlations are measured with the ALICE apparatus in pp collisions at s√=13 TeV to explore strangeness- and multiplicity-related effects in the fragmentation of jets and the transition regime between bulk and hard production, probed with the condition that a strange meson (KS0) or baryon (Λ) with transverse momentum pT>3 GeV/c is produced. Azimuthal correlations between kaons or Λ hyperons with other hadrons are presented at midrapidity for a broad range of the trigger (3<ptriggT<20 GeV/c) and associated particle pT (1 GeV/c <passocT<ptriggT), for minimum-bias events and as a function of the event multiplicity. The near- and away-side peak yields are compared for the case of either KS0 or Λ(Λ¯¯¯¯) being the trigger particle with that of inclusive hadrons (a sample dominated by pions). In addition, the measurements are compared with predictions from PYTHIA 8 and EPOS LHC event generators.
We report on the inclusive J/ψ production cross section measured at the CERN Large Hadron Collider in proton–proton collisions at a center-of-mass energy s√ = 13 TeV. The J/ψ mesons are reconstructed in the e+e− decay channel and the measurements are performed at midrapidity (|y|<0.9) in the transverse-momentum interval 0<pT<40 GeV/c, using a minimum-bias data sample corresponding to an integrated luminosity Lint=32.2 nb−1 and an Electromagnetic Calorimeter triggered data sample with Lint=8.3 pb−1. The pT-integrated J/ψ production cross section at midrapidity, computed using the minimum-bias data sample, is dσ/dy|y=0=8.97±0.24 (stat)±0.48 (syst)±0.15 (lumi) μb. An approximate logarithmic dependence with the collision energy is suggested by these results and available world data, in agreement with model predictions. The integrated and pT-differential measurements are compared with measurements in pp collisions at lower energies and with several recent phenomenological calculations based on the non-relativistic QCD and Color Evaporation models.