Characterizing Heterogeneity in Neuroimaging, Cognition, Clinical Symptoms, and Genetics Among Patients With Late-Life Depression

Importance: Late-life depression (LLD) is characterized by considerable heterogeneity in clinical manifestation. Unraveling such heterogeneity might aid in elucidating etiological mechanisms and support precision and individualized medicine. Objective: To cross-sectionally and longitudinally delineate disease-related heterogeneity in LLD associated with neuroanatomy, cognitive functioning, clinical symptoms, and genetic profiles. Design, Setting, and Participants: The Imaging-Based Coordinate System for Aging and Neurodegenerative Diseases (iSTAGING) study is an international multicenter consortium investigating brain aging in pooled and harmonized data from 13 studies with more than 35 000 participants, including a subset of individuals with major depressive disorder. Multimodal data from a multicenter sample (N = 996), including neuroimaging, neurocognitive assessments, and genetics, were analyzed in this study. A semisupervised clustering method (heterogeneity through discriminative analysis) was applied to regional gray matter (GM) brain volumes to derive dimensional representations. Data were collected from July 2017 to July 2020 and analyzed from July 2020 to December 2021. Main Outcomes and Measures: Two dimensions were identified to delineate LLD-associated heterogeneity in voxelwise GM maps, white matter (WM) fractional anisotropy, neurocognitive functioning, clinical phenotype, and genetics. Results: A total of 501 participants with LLD (mean [SD] age, 67.39 [5.56] years; 332 women) and 495 healthy control individuals (mean [SD] age, 66.53 [5.16] years; 333 women) were included. Patients in dimension 1 demonstrated relatively preserved brain anatomy without WM disruptions relative to healthy control individuals. In contrast, patients in dimension 2 showed widespread brain atrophy and WM integrity disruptions, along with cognitive impairment and higher depression severity. Moreover, 1 de novo independent genetic variant (rs13120336; chromosome: 4, 186387714; minor allele, G) was significantly associated with dimension 1 (odds ratio, 2.35; SE, 0.15; P = 3.14 ×10⁸) but not with dimension 2. The 2 dimensions demonstrated significant single-nucleotide variant–based heritability of 18% to 27% within the general population (N = 12 518 in UK Biobank). In a subset of individuals having longitudinal measurements, those in dimension 2 experienced a more rapid longitudinal change in GM and brain age (Cohen ƒ² = 0.03; P = .02) and were more likely to progress to Alzheimer disease (Cohen ƒ² = 0.03; P = .03) compared with those in dimension 1 (N = 1431 participants and 7224 scans from the Alzheimer’s Disease Neuroimaging Initiative [ADNI], Baltimore Longitudinal Study of Aging [BLSA], and Biomarkers for Older Controls at Risk for Dementia [BIOCARD] data sets). Conclusions and Relevance: This study characterized heterogeneity in LLD into 2 dimensions with distinct neuroanatomical, cognitive, clinical, and genetic profiles. This dimensional approach provides a potential mechanism for investigating the heterogeneity of LLD and the relevance of the latent dimensions to possible disease mechanisms, clinical outcomes, and responses to interventions

Measurement of the B0_s semileptonic branching ratio to an orbitally excited D_s** state, Br(B0_s -> Ds1(2536) mu nu)

In a data sample of approximately 1.3 fb-1 collected with the D0 detector between 2002 and 2006, the orbitally excited charm state D_s1(2536) has been observed with a measured mass of 2535.7 +/- 0.6 (stat) +/- 0.5 (syst) MeV via the decay mode B0_s -> D_s1(2536) mu nu X. A first measurement is made of the branching ratio product Br(b(bar) -> D_s1(2536) mu nu X).Br(D_s1(2536)->D* K0_S). Assuming that D_s1(2536) production in semileptonic decay is entirely from B0_s, an extraction of the semileptonic branching ratio Br(B0_s -> D_s1(2536) mu nu X) is made.Comment: 7 pages, 2 figures, LaTeX, version with minor changes as accepted by Phys. Rev. Let

Simultaneous measurement of the ratio B(t->Wb)/B(t->Wq) and the top quark pair production cross section with the D0 detector at sqrt(s)=1.96 TeV

We present the first simultaneous measurement of the ratio of branching fractions, R=B(t->Wb)/B(t->Wq), with q being a d, s, or b quark, and the top quark pair production cross section sigma_ttbar in the lepton plus jets channel using 0.9 fb-1 of ppbar collision data at sqrt(s)=1.96 TeV collected with the D0 detector. We extract R and sigma_ttbar by analyzing samples of events with 0, 1 and >= 2 identified b jets. We measure R = 0.97 +0.09-0.08 (stat+syst) and sigma_ttbar = 8.18 +0.90-0.84 (stat+syst)} +/-0.50 (lumi) pb, in agreement with the standard model prediction.Comment: submitted to Phys.Rev.Letter

Measurement of the forward-backward charge asymmetry and extraction of sin^2Theta^{eff}_W in ppbar -> Z/\gamma^{*}+X -> e+e+X events produced at \sqrt{s}=1.96 TeV

We present a measurement of the forward-backward charge asymmetry ($A_{FB}$) in $p\bar{p} \to Z/\gamma^{*}+X \to e^+e^-+X$ events at a center-of-mass energy of 1.96 TeV using 1.1 fb$^{-1}$ of data collected with the D0 detector at the Fermilab Tevatron collider. $A_{FB}$ is measured as a function of the invariant mass of the electron-positron pair, and found to be consistent with the standard model prediction. We use the $A_{FB}$ measurement to extract the effective weak mixing angle $sin^2Theta^{eff}_W = 0.2327 \pm 0.0018 (stat.) \pm 0.0006 (syst.)$.Comment: 7 Pages, 1 Figure, 3 Tables, Accepted by Phys. Rev. Let

Search for charged Higgs bosons decaying to top and bottom quarks in ppbar collisions

We describe a search for production of a charged Higgs boson, q \bar{q'} -> H^+, reconstructed in the t\bar{b} final state in the mass range 180 <= M_{H^+} <= 300 GeV. The search was undertaken at the Fermilab Tevatron collider with a center-of-mass energy sqrt{s} = 1.96 TeV and uses 0.9 fb^{-1} of data collected with the D0 detector. We find no evidence for charged Higgs boson production and set upper limits on the production cross section in the Types I, II and III two-Higgs-doublet models (2HDMs). An excluded region in the (M_{H^+},tan\beta) plane for Type I 2HDM is presented.Comment: Submitted to Phys. Rev. Letter

Measurement of the lifetime of the B_c meson in the semileptonic decay channel

Using approximately 1.3 fb-1 of data collected by the D0 detector between 2002 and 2006, we measure the lifetime of the B_c meson in the B_c -> J/psi mu nu X final state. A simultaneous unbinned likelihood fit to the J/\psi+mu invariant mass and lifetime distributions yields a signal of 881 +/- 80 (stat) candidates and a lifetime measurement of \tau(B_c) = 0.448 +0.038 -0.036 (stat) +/- 0.032 (syst) ps.Comment: 7 pages, 2 figures, submitted to Phys. Rev. Let

Search for anomalous \boldmath{Wtb} couplings in single top quark production

In 0.9 fb$^{-1}$ of $p \bar p$ collisions, D0 has observed an excess of events with an isolated lepton, missing transve rse momentum, and two to four jets. This excess is consistent with single top quark production. We examine these data to study the Lorentz structure of the $Wtb$ coupling. The standard model predicts a left-handed vector coupling at the $Wt b$ vertex. The most general lowest dimension, CP-conserving Lagrangian admits right-handed vector and left- or right-h anded tensor couplings as well. We find that the data prefer the left-handed vector coupling and set upper limits on the anomalous couplings. These are the first direct constraints on a general $Wtb$ interaction and the first direct limits on left- and right-handed tensor couplings.Comment: 7 pages, 4 figure

Measurement of the electron charge asymmetry in ppbar->W+X->enu+X events at sqrt{s}=1.96 TeV

We present a measurement of the electron charge asymmetry in ppbar->W+X->enu+X events at a center of mass energy of 1.96 TeV using 0.75 fb-1 of data collected with the D0 detector at the Fermilab Tevatron Collider. The asymmetry is measured as a function of the electron transverse momentum and pseudorapidity in the interval (-3.2, 3.2) and is compared with expectations from next-to-leading order calculations in perturbative quantum chromodynamics. These measurements will allow more accurate determinations of the proton parton distribution functions.Comment: 7 pages, 3 figures, Fermilab-Pub-08/249-E, submitted to Phys. Rev. Let

Observation of ZZ production in ppbar collisions at sqrt(s) = 1.96 TeV

We present an observation for ZZ -> l+l-l'+l'- (l, l' = e or mu) production in ppbar collisions at a center-of-mass energy of sqrt(s) = 1.96 TeV. Using 1.7 fb-1 of data collected by the D0 experiment at the Fermilab Tevatron Collider, we observe three candidate events with an expected background of 0.14 +0.03 -0.02 events. The significance of this observation is 5.3 standard deviations. The combination of D0 results in this channel, as well as in ZZ -> l+l-nunubar, yields a significance of 5.7 standard deviations and a combined cross section of sigma(ZZ) = 1.60 +/- 0.63 (stat.) +0.16 -0.17 (syst.) pb.Comment: 7 pages, 1 figure, 2 tables Modified slightly following review proces

A search for the standard model Higgs boson in the missing energy and acoplanar b-jet topology at sqrt(s) = 1.96 TeV

We report a search for the standard model Higgs boson in the missing energy and acoplanar b-jet topology, using an integrated luminosity of 0.93 inverse femtobarn recorded by the D0 detector at the Fermilab Tevatron Collider. The analysis includes signal contributions from pp->ZH->nu nu b b, as well as from WH production in which the charged lepton from the W boson decay is undetected. Neural networks are used to separate signal from background. In the absence of a signal, we set limits on the cross section of pp->VH times the branching ratio of H->bb at the 95% C.L. of 2.6 - 2.3 pb, for Higgs boson masses in the range 105 - 135 GeV, where V=W,Z. The corresponding expected limits range from 2.8 pb - 2.0 pb.Comment: Submitted to Phys. Rev. Letter