Systemic perturbations of the kynurenine pathway precede progression to dementia independently of amyloid-β

Increasing evidence suggests that kynurenine pathway (KP) dyshomeostasis may promote disease progression in dementia. Studies in Alzheimer's disease (AD) patients confirm KP dyshomeostasis in plasma and cerebrospinal fluid (CSF) which correlates with amyloid-β and tau pathology. Herein, we performed the first comprehensive study assessing baseline levels of KP metabolites in participants enrolling in the Australian Imaging Biomarkers Flagship Study of Aging. Our purpose was to test the hypothesis that changes in KP metabolites may be biomarkers of dementia processes that are largely silent. We used a cross-sectional analytical approach to assess non-progressors (N = 73); cognitively normal (CN) or mild cognitive impairment (MCI) participants at baseline and throughout the study, and progressors (N = 166); CN or MCI at baseline but progressing to either MCI or AD during the study. Significant KP changes in progressors included increased 3-hydroxyanthranilic acid (3-HAA) and 3-hydroxyanthranilic acid/anthranilic acid (3-HAA/AA) ratio, the latter having the largest effect on the odds of an individual being a progressor (OR 35.3; 95% CI between 14 and 104). 3-HAA levels were hence surprisingly bi-phasic, high in progressors but low in non-progressors or participants who had already transitioned to MCI or dementia. This is a new, unexpected and interesting result, as most studies of the KP in neurodegenerative disease show reduced 3-HAA/AA ratio after diagnosis. The neuroprotective metabolite picolinic acid was also significantly decreased while the neurotoxic metabolite 3-hydroxykynurenine increased in progressors. These results were significant even after adjustment for confounders. Considering the magnitude of the OR to predict change in cognition, it is important that these findings are replicated in other populations. Independent validation of our findings may confirm the utility of 3-HAA/AA ratio to predict change in cognition leading to dementia in clinical settings

Recovering Joys Law as a Function of Solar Cycle, Hemisphere, and Longitude

Bipolar active regions in both hemispheres tend to be tilted with respect to the East West equator of the Sun in accordance with Joys law that describes the average tilt angle as a function of latitude. Mt. Wilson observatory data from 1917 to 1985 are used to analyze the active-region tilt angle as a function of solar cycle, hemisphere, and longitude, in addition to the more common dependence on latitude. Our main results are as follows: i) We recommend a revision of Joys law toward a weaker dependence on latitude (slope of 0.13 to 0.26) and without forcing the tilt to zero at the Equator. ii) We determine that the hemispheric mean tilt value of active regions varies with each solar cycle, although the noise from a stochastic process dominates and does not allow for a determination of the slope of Joys law on an 11-year time scale. iii) The hemispheric difference in mean tilt angles, 1.1 degrees + 0.27, over Cycles 16 to 21 was significant to a three-sigma level, with average tilt angles in the northern and southern hemispheres of 4.7 degrees + 0.26 and 3.6 degrees + 0.27 respectively. iv) Area-weighted mean tilt angles normalized by latitude for Cycles 15 to 21 anticorrelate with cycle strength for the southern hemisphere and whole-Sun data, confirming previous results by Dasi-Espuig, Solanki, Krivova, et al. (2010, Astron. Astrophys. 518, A7). The northern hemispheric mean tilt angles do not show a dependence on cycle strength. vi) Mean tilt angles do not show a dependence on longitude for any hemisphere or cycle. In addition, the standard deviation of the mean tilt is 29 to 31 degrees for all cycles and hemispheres indicating that the scatter is due to the same consistent process even if the mean tilt angles vary.Comment: 13 pages, 4 figures, 3 table

Measurement of the View the tt production cross-section using eμ events with b-tagged jets in pp collisions at √s = 13 TeV with the ATLAS detector

This paper describes a measurement of the inclusive top quark pair production cross-section (σtt¯) with a data sample of 3.2 fb−1 of proton–proton collisions at a centre-of-mass energy of √s = 13 TeV, collected in 2015 by the ATLAS detector at the LHC. This measurement uses events with an opposite-charge electron–muon pair in the final state. Jets containing b-quarks are tagged using an algorithm based on track impact parameters and reconstructed secondary vertices. The numbers of events with exactly one and exactly two b-tagged jets are counted and used to determine simultaneously σtt¯ and the efficiency to reconstruct and b-tag a jet from a top quark decay, thereby minimising the associated systematic uncertainties. The cross-section is measured to be: σtt¯ = 818 ± 8 (stat) ± 27 (syst) ± 19 (lumi) ± 12 (beam) pb, where the four uncertainties arise from data statistics, experimental and theoretical systematic effects, the integrated luminosity and the LHC beam energy, giving a total relative uncertainty of 4.4%. The result is consistent with theoretical QCD calculations at next-to-next-to-leading order. A fiducial measurement corresponding to the experimental acceptance of the leptons is also presented

Search for TeV-scale gravity signatures in high-mass final states with leptons and jets with the ATLAS detector at sqrt [ s ] = 13TeV

A search for physics beyond the Standard Model, in final states with at least one high transverse momentum charged lepton (electron or muon) and two additional high transverse momentum leptons or jets, is performed using 3.2 fb−1 of proton–proton collision data recorded by the ATLAS detector at the Large Hadron Collider in 2015 at √s = 13 TeV. The upper end of the distribution of the scalar sum of the transverse momenta of leptons and jets is sensitive to the production of high-mass objects. No excess of events beyond Standard Model predictions is observed. Exclusion limits are set for models of microscopic black holes with two to six extra dimensions

Search for dark matter produced in association with a hadronically decaying vector boson in pp collisions at sqrt (s) = 13 TeV with the ATLAS detector

A search is presented for dark matter produced in association with a hadronically decaying W or Z boson using 3.2 fb−1 of pp collisions at View the MathML sources=13 TeV recorded by the ATLAS detector at the Large Hadron Collider. Events with a hadronic jet compatible with a W or Z boson and with large missing transverse momentum are analysed. The data are consistent with the Standard Model predictions and are interpreted in terms of both an effective field theory and a simplified model containing dark matter

Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000–17 : analysis for the Global Burden of Disease Study 2017

Background Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. Methods We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates. Findings The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1–65·8), 17·4% (7·7–28·4), and 59·5% (34·2–86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage. Interpretation By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health

Measurement of the double-differential high-mass Drell-Yan cross section in pp collisions at √s = 8 TeV with the ATLAS detector

This paper presents a measurement of the double-differential cross section for the Drell-Yan Z/γ∗ → ℓ+ℓ− and photon-induced γγ → ℓ+ℓ− processes where ℓ is an electron or muon. The measurement is performed for invariant masses of the lepton pairs, mℓℓ, between 116 GeV and 1500 GeV using a sample of 20.3 fb−1 of pp collisions data at centre-of-mass energy of √s = 8 TeV collected by the ATLAS detector at the LHC in 2012. The data are presented double differentially in invariant mass and absolute dilepton rapidity as well as in invariant mass and absolute pseudorapidity separation of the lepton pair. The single-differential cross section as a function of mℓℓ is also reported. The electron and muon channel measurements are combined and a total experimental precision of better than 1% is achieved at low mℓℓ. A comparison to next-to-next-to-leading order perturbative QCD predictions using several recent parton distribution functions and including next-to-leading order electroweak effects indicates the potential of the data to constrain parton distribution functions. In particular, a large impact of the data on the photon PDF is demonstrated

Search for resonances in the mass distribution of jet pairs with one or two jets identified as b-jets in proton–proton collisions at √s=13TeV with the ATLAS detector

Searches for high-mass resonances in the dijet invariant mass spectrum with one or two jets identi-fied as b-jets are performed using an integrated luminosity of 3.2fb−1of proton–proton collisions with a centre-of-mass energy of √s=13TeVrecorded by the ATLAS detector at the Large Hadron Collider. Noevidence of anomalous phenomena is observed in the data, which are used to exclude, at 95%credibility level, excited b∗quarks with masses from 1.1TeVto 2.1TeVand leptophobic Z bosons with masses from 1.1TeVto 1.5TeV. Contributions of a Gaussian signal shape with effective cross sections ranging from approximately 0.4 to 0.001pb are also excluded in the mass range 1.5–5.0TeV

Search for high-mass new phenomena in the dilepton final state using proton–proton collisions at View the MathML sources=13TeV with the ATLAS detector

A search is conducted for both resonant and non-resonant high-mass new phenomena in dielectron and dimuon final states. The search uses View the MathML source3.2fb−1 of proton–proton collision data, collected at View the MathML sources=13TeV by the ATLAS experiment at the LHC in 2015. The dilepton invariant mass is used as the discriminating variable. No significant deviation from the Standard Model prediction is observed; therefore limits are set on the signal model parameters of interest at 95% credibility level. Upper limits are set on the cross-section times branching ratio for resonances decaying to dileptons, and the limits are converted into lower limits on the resonance mass, ranging between 2.74 TeV and 3.36 TeV, depending on the model. Lower limits on the ℓℓqqℓℓqq contact interaction scale are set between 16.7 TeV and 25.2 TeV, also depending on the mode

Measurement of the top quark mass in the tt→ dilepton channel from √s = 8 TeV ATLAS data

The top quark mass is measured in the tt¯ → dilepton channel (lepton = e,μ) using ATLAS data recorded in the year 2012 at the LHC. The data were taken at a proton proton centre-of-mass energy of √s = 8 TeV and correspond to an integrated luminosity of about 20.2 fb−1. Exploiting the template method, and using the distribution of invariant masses of lepton–b-jet pairs, the top quark mass is measured to be mtop = 172.99±0.41 (stat) ±0.74 (syst) GeV, with a total uncertainty of 0.84 GeV. Finally, a combination with previous ATLAS mtop measurements from √s = 7 TeV data in the tt¯ → dilepton and tt¯ → lepton + jets channels results in mtop = 172.84±0.34 (stat)±0.61 (syst) GeV, with a total uncertainty of 0.70 GeV