Pattern and degree of individual brain atrophy predicts dementia onset in dominantly inherited Alzheimer's disease

Introduction: Asymptomatic and mildly symptomatic dominantly inherited Alzheimer's disease mutation carriers (DIAD-MC) are ideal candidates for preventative treatment trials aimed at delaying or preventing dementia onset. Brain atrophy is an early feature of DIAD-MC and could help predict risk for dementia during trial enrollment. Methods: We created a dementia risk score by entering standardized gray-matter volumes from 231 DIAD-MC into a logistic regression to classify participants with and without dementia. The score's predictive utility was assessed using Cox models and receiver operating curves on a separate group of 65 DIAD-MC followed longitudinally. Results: Our risk score separated asymptomatic versus demented DIAD-MC with 96.4% (standard error = 0.02) and predicted conversion to dementia at next visit (hazard ratio = 1.32, 95% confidence interval [CI: 1.15, 1.49]) and within 2 years (area under the curve = 90.3%, 95% CI [82.3%–98.2%]) and improved prediction beyond established methods based on familial age of onset. Discussion: Individualized risk scores based on brain atrophy could be useful for establishing enrollment criteria and stratifying DIAD-MC participants for prevention trials

Patterns of deep-sea genetic connectivity in the New Zealand region : implications for management of benthic ecosystems

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 7 (2012): e49474, doi:10.1371/journal.pone.0049474.Patterns of genetic connectivity are increasingly considered in the design of marine protected areas (MPAs) in both shallow and deep water. In the New Zealand Exclusive Economic Zone (EEZ), deep-sea communities at upper bathyal depths (<2000 m) are vulnerable to anthropogenic disturbance from fishing and potential mining operations. Currently, patterns of genetic connectivity among deep-sea populations throughout New Zealand’s EEZ are not well understood. Using the mitochondrial Cytochrome Oxidase I and 16S rRNA genes as genetic markers, this study aimed to elucidate patterns of genetic connectivity among populations of two common benthic invertebrates with contrasting life history strategies. Populations of the squat lobster Munida gracilis and the polychaete Hyalinoecia longibranchiata were sampled from continental slope, seamount, and offshore rise habitats on the Chatham Rise, Hikurangi Margin, and Challenger Plateau. For the polychaete, significant population structure was detected among distinct populations on the Chatham Rise, the Hikurangi Margin, and the Challenger Plateau. Significant genetic differences existed between slope and seamount populations on the Hikurangi Margin, as did evidence of population differentiation between the northeast and southwest parts of the Chatham Rise. In contrast, no significant population structure was detected across the study area for the squat lobster. Patterns of genetic connectivity in Hyalinoecia longibranchiata are likely influenced by a number of factors including current regimes that operate on varying spatial and temporal scales to produce potential barriers to dispersal. The striking difference in population structure between species can be attributed to differences in life history strategies. The results of this study are discussed in the context of existing conservation areas that are intended to manage anthropogenic threats to deep-sea benthic communities in the New Zealand region.This work was funded in part by a Fulbright Fellowship administered by Fulbright New Zealand and the U.S. Department of State, awarded in 2011 to EKB. Funding and support for research expedition was provided by Land Information New Zealand, New Zealand Ministry of Fisheries, NIWA, Census of Marine Life on Seamounts (CenSeam), and the Foundation for Research, Science and Technology. Other research funding was provided by the New Zealand Ministry of Science and Innovation project “Impacts of resource use on vulnerable deep-sea communities” (FRST contract CO1X0906), the National Science Foundation (OCE-0647612), and the Deep Ocean Exploration Institute (Fellowship support to TMS)

Fitness Consequences of Advanced Ancestral Age over Three Generations in Humans

A rapid rise in age at parenthood in contemporary societies has increased interest in reports of higher prevalence of de novo mutations and health problems in individuals with older fathers, but the fitness consequences of such age effects over several generations remain untested. Here, we use extensive pedigree data on seven pre-industrial Finnish populations to show how the ages of ancestors for up to three generations are associated with fitness traits. Individuals whose fathers, grandfathers and great-grandfathers fathered their lineage on average under age 30 were ~13% more likely to survive to adulthood than those whose ancestors fathered their lineage at over 40 years. In addition, females had a lower probability of marriage if their male ancestors were older. These findings are consistent with an increase of the number of accumulated de novo mutations with male age, suggesting that deleterious mutations acquired from recent ancestors may be a substantial burden to fitness in humans. However, possible non-mutational explanations for the observed associations are also discussed

Measurements of differential cross-sections in top-quark pair events with a high transverse momentum top quark and limits on beyond the Standard Model contributions to top-quark pair production with the ATLAS detector at √s = 13 TeV

Cross-section measurements of top-quark pair production where the hadronically decaying top quark has transverse momentum greater than 355 GeV and the other top quark decays into ℓνb are presented using 139 fb−1 of data collected by the ATLAS experiment during proton-proton collisions at the LHC. The fiducial cross-section at s = 13 TeV is measured to be σ = 1.267 ± 0.005 ± 0.053 pb, where the uncertainties reflect the limited number of data events and the systematic uncertainties, giving a total uncertainty of 4.2%. The cross-section is measured differentially as a function of variables characterising the tt¯ system and additional radiation in the events. The results are compared with various Monte Carlo generators, including comparisons where the generators are reweighted to match a parton-level calculation at next-to-next-to-leading order. The reweighting improves the agreement between data and theory. The measured distribution of the top-quark transverse momentum is used to search for new physics in the context of the effective field theory framework. No significant deviation from the Standard Model is observed and limits are set on the Wilson coefficients of the dimension-six operators OtG and Otq(8), where the limits on the latter are the most stringent to date. [Figure not available: see fulltext.]

A Deep Neural Network for Simultaneous Estimation of b Jet Energy and Resolution

We describe a method to obtain point and dispersion estimates for the energies of jets arising from b quarks produced in proton-proton collisions at an energy of s = 13 TeV at the CERN LHC. The algorithm is trained on a large sample of simulated b jets and validated on data recorded by the CMS detector in 2017 corresponding to an integrated luminosity of 41 fb - 1 . A multivariate regression algorithm based on a deep feed-forward neural network employs jet composition and shape information, and the properties of reconstructed secondary vertices associated with the jet. The results of the algorithm are used to improve the sensitivity of analyses that make use of b jets in the final state, such as the observation of Higgs boson decay to b b ¯

Search for neutral long-lived particles in pp collisions at s√ = 13 TeV that decay into displaced hadronic jets in the ATLAS calorimeter

A search for decays of pair-produced neutral long-lived particles (LLPs) is presented using 139 fb−1 of proton-proton collision data collected by the ATLAS detector at the LHC in 2015–2018 at a centre-of-mass energy of 13 TeV. Dedicated techniques were developed for the reconstruction of displaced jets produced by LLPs decaying hadronically in the ATLAS hadronic calorimeter. Two search regions are defined for different LLP kinematic regimes. The observed numbers of events are consistent with the expected background, and limits for several benchmark signals are determined. For a SM Higgs boson with a mass of 125 GeV, branching ratios above 10% are excluded at 95% confidence level for values of c times LLP mean proper lifetime in the range between 20 mm and 10 m depending on the model. Upper limits are also set on the cross-section times branching ratio for scalars with a mass of 60 GeV and for masses between 200 GeV and 1 TeV

Studies of B_{s2}^{*} (5840)⁰ and B_{s1} (5830)⁰ mesons including the observation of the B_{s2}^{*} (5840)⁰ → B⁰K_{s}^{0} decay in proton-proton collisions at √s = 8 TeV

Measurements of B_{s2}^{*} (5840)⁰ and B_{s1} (5840)⁰ mesons are performed using a data sample of proton-proton collisions corresponding to an integrated luminosity of 19.6 fb⁻¹, collected with the CMS detector at the LHC at a centre-of-mass energy of 8 TeV. The analysis studies P-wave B_{s}^{0} meson decays into B^{(*)}⁺K⁻ and B^{(*)}⁰K_{s}^{0}, where the B⁺ and B⁰ mesons are identified using the decays B⁺ → J/φK⁺ and B⁰ → J/φK* (892)⁰. The masses of the P-wave B_{s}^{0} meson states are measured and the natural width of the B_{*}^{s2} (5840)⁰ state is determined. The first measurement of the mass difference between the charged and neutral B* mesons is also presented. The B_{*}^{s2} (5840)⁰ decay to B⁰K_{s}^{0} is observed, together with a measurement of its branching fraction relative to the B_{s2}^{*} (5840)⁰ → B⁺K⁻ decay