| 1. |
|
|
| 2. |
- Aartsen, M. G., et al.
(författare)
-
Searches for Sterile Neutrinos with the IceCube Detector
- 2016
-
Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 117:7
-
Tidskriftsartikel (refereegranskat)abstract
- The IceCube neutrino telescope at the South Pole has measured the atmospheric muon neutrino spectrum as a function of zenith angle and energy in the approximate 320 GeV to 20 TeV range, to search for the oscillation signatures of light sterile neutrinos. No evidence for anomalous nu(mu) or (nu) over bar (mu) disappearance is observed in either of two independently developed analyses, each using one year of atmospheric neutrino data. New exclusion limits are placed on the parameter space of the 3 + 1 model, in which muon antineutrinos experience a strong Mikheyev-Smirnov-Wolfenstein-resonant oscillation. The exclusion limits extend to sin(2)2 theta(24) <= 0.02 at Delta m(2) similar to 0.3 eV(2) at the 90% confidence level. The allowed region from global analysis of appearance experiments, including LSND and MiniBooNE, is excluded at approximately the 99% confidence level for the global best-fit value of vertical bar U-e4 vertical bar(2).
|
|
| 3. |
- Edgecock, T. R., et al.
(författare)
-
High intensity neutrino oscillation facilities in Europe
- 2013
-
Ingår i: Physical Review Special Topics - Accelerators and Beams. - : American Physical Society. - 1098-4402. ; 16:2, s. 021002-
-
Tidskriftsartikel (refereegranskat)abstract
- The EUROnu project has studied three possible options for future, high intensity neutrino oscillation facilities in Europe. The first is a Super Beam, in which the neutrinos come from the decay of pions created by bombarding targets with a 4 MW proton beam from the CERN High Power Superconducting Proton Linac. The far detector for this facility is the 500 kt MEMPHYS water Cherenkov, located in the Frejus tunnel. The second facility is the Neutrino Factory, in which the neutrinos come from the decay of mu(+) and mu(-) beams in a storage ring. The far detector in this case is a 100 kt magnetized iron neutrino detector at a baseline of 2000 km. The third option is a Beta Beam, in which the neutrinos come from the decay of beta emitting isotopes, in particular He-6 and Ne-18, also stored in a ring. The far detector is also the MEMPHYS detector in the Frejus tunnel. EUROnu has undertaken conceptual designs of these facilities and studied the performance of the detectors. Based on this, it has determined the physics reach of each facility, in particular for the measurement of CP violation in the lepton sector, and estimated the cost of construction. These have demonstrated that the best facility to build is the Neutrino Factory. However, if a powerful proton driver is constructed for another purpose or if the MEMPHYS detector is built for astroparticle physics, the Super Beam also becomes very attractive.
|
|
| 4. |
- Armengaud, E., et al.
(författare)
-
Physics potential of the International Axion Observatory (IAXO)
- 2019
-
Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :6
-
Tidskriftsartikel (refereegranskat)abstract
- We review the physics potential of a next generation search for solar axions: the International Axion Observatory (IAXO). Endowed with a sensitivity to discover axion-like particles (ALPs) with a coupling to photons as small as g(a gamma) similar to 10(-12) GeV-1, or to electrons g(ae) similar to 10(-13), IAXO has the potential to find the QCD axion in the 1 meV similar to 1 eV mass range where it solves the strong CP problem, can account for the cold dark matter of the Universe and be responsible for the anomalous cooling observed in a number of stellar systems. At the same time, IAXO will have enough sensitivity to detect lower mass axions invoked to explain: 1) the origin of the anomalous transparency of the Universe to gamma-rays, 2) the observed soft X-ray excess from galaxy clusters or 3) some inflationary models. In addition, we review string theory axions with parameters accessible by IAXO and discuss their potential role in cosmology as Dark Matter and Dark Radiation as well as their connections to the above mentioned conundrums.
|
|
| 5. |
- Alemany, S., et al.
(författare)
-
Associations between air pollution and biomarkers of Alzheimer's disease in cognitively unimpaired individuals
- 2021
-
Ingår i: Environment International. - : Elsevier BV. - 0160-4120. ; 157
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Air quality contributes to incidence of Alzheimer's disease (AD) although the underlying neurobiological mechanisms are unclear. This study was aimed to examine the association between air pollution and concentrations of cerebrospinal fluid (CSF) AD biomarkers and amyloid-beta (A beta) deposition. Participants and methods The sample included 156 cognitively unimpaired adults aged 57 years (61 at biomarkers assessment) with increased risk of AD from the ALFA + Study. We examined CSF levels of A beta 42, A beta 40, p-Tau, t-Tau, neurofilament light (NfL) and cerebral amyloid load (Centiloid). A Land Use Regression model from 2009 was used to estimate residential exposure to air pollutants including nitrogen dioxide (NO2,) and particulate matter (PM2.5, PM2.5 abs, PM10). This model was considered a surrogate of long-term exposure until time of data collection in 2013-2014. Participants have resided in the same residence for at least the previous 3 years. Multiple linear regression models were used to estimate associations between air pollutants and biomarkers. The effect modification by CSF A beta status and APOE-epsilon 4 carriership was also assessed. Results: A consistent pattern of results indicated that greater exposure to NO2 and PM2.5 absorbance was associated with higher levels of brain A beta deposition, while greater exposure to PM10 and PM(2.5)was associated with higher levels of CSF NfL. Most associations were driven by individuals that were A beta-positive. Although APOE-epsilon 4 status did not significantly modify these associations, the effect of air pollutants exposure on CSF NfL levels was stronger in APOE-epsilon 4 carriers. Conclusion: In a population of cognitively unimpaired adults with increased risk of AD, long-term exposure to air pollution was associated with higher levels in biomarkers of AD pathology. While further research is granted to elucidate the mechanisms involved in such associations, our results reinforce the role of air pollution as an environmental risk factor for AD.
|
|
| 6. |
|
|
| 7. |
- Grau-Rivera, O., et al.
(författare)
-
Association of weight change with cerebrospinal fluid biomarkers and amyloid positron emission tomography in preclinical Alzheimer's disease
- 2021
-
Ingår i: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundRecognizing clinical manifestations heralding the development of Alzheimer's disease (AD)-related cognitive impairment could improve the identification of individuals at higher risk of AD who may benefit from potential prevention strategies targeting preclinical population. We aim to characterize the association of body weight change with cognitive changes and AD biomarkers in cognitively unimpaired middle-aged adults.MethodsThis prospective cohort study included data from cognitively unimpaired adults from the ALFA study (n=2743), a research platform focused on preclinical AD. Cognitive and anthropometric data were collected at baseline between April 2013 and November 2014. Between October 2016 and February 2020, 450 participants were visited in the context of the nested ALFA+ study and underwent cerebrospinal fluid (CSF) extraction and acquisition of positron emission tomography images with [F-18]flutemetamol (FTM-PET). From these, 408 (90.1%) were included in the present study. We used data from two visits (average interval 4.1years) to compute rates of change in weight and cognitive performance. We tested associations between these variables and between weight change and categorical and continuous measures of CSF and neuroimaging AD biomarkers obtained at follow-up. We classified participants with CSF data according to the AT (amyloid, tau) system and assessed between-group differences in weight change.ResultsWeight loss predicted a higher likelihood of positive FTM-PET visual read (OR 1.27, 95% CI 1.00-1.61, p=0.049), abnormal CSF p-tau levels (OR 1.50, 95% CI 1.19-1.89, p=0.001), and an A+T+ profile (OR 1.64, 95% CI 1.25-2.20, p=0.001) and was greater among participants with an A+T+ profile (p<0.01) at follow-up. Weight change was positively associated with CSF A42/40 ratio (beta =0.099, p=0.032) and negatively associated with CSF p-tau (beta=-0.141, p=0.005), t-tau (beta=-0.147 p=0.004) and neurogranin levels (beta=-0.158, p=0.002). In stratified analyses, weight loss was significantly associated with higher t-tau, p-tau, neurofilament light, and neurogranin, as well as faster cognitive decline in A+ participants only.ConclusionsWeight loss predicts AD CSF and PET biomarker results and may occur downstream to amyloid-beta accumulation in preclinical AD, paralleling cognitive decline. Accordingly, it should be considered as an indicator of increased risk of AD-related cognitive impairment.Trial registrationNCT01835717, NCT02485730, NCT02685969.
|
|
| 8. |
- Mila-Aloma, M., et al.
(författare)
-
Amyloid beta, tau, synaptic, neurodegeneration, and glial biomarkers in the preclinical stage of the Alzheimer's continuum
- 2020
-
Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:10, s. 1358-1371
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: The biological pathways involved in the preclinical stage of the Alzheimer's continuum are not well understood. Methods: We used NeuroToolKit and Elecsys (R) immunoassays to measure cerebrospinal fluid (CSF) amyloid-beta (A beta)42, A beta 40, phosphorylated tau (p-tau), total tau (t-tau), neurofilament light (NfL), neurogranin, sTREM2, YKL40, GFAP, IL6, S100, and alpha-synuclein in cognitively unimpaired participants of the ALFA+ study, many within the Alzheimer's continuum. Results: CSF t-tau, p-tau, and neurogranin increase throughout aging only in A beta-positive individuals, whereas NfL and glial biomarkers increase with aging regardless of A beta status. We modelled biomarker changes as a function of CSF A beta 42/40, p-tau and p-tau/A beta 42 as proxies of disease progression. The first change observed in the Alzheimer's continuum was a decrease in the CSF A4 beta 42/40 ratio. This is followed by a steep increase in CSF p-tau; t-tau; neurogranin; and, to a lesser extent, in NfL and glial biomarkers. Discussion: Multiple biological pathways are altered and could be targeted very early in the Alzheimer's continuum.
|
|
| 9. |
- Mila-Aloma, M., et al.
(författare)
-
Cognitively unimpaired individuals with a low burden of A beta pathology have a distinct CSF biomarker profile
- 2021
-
Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Understanding the changes that occur in the transitional stage between absent and overt amyloid-beta (A beta) pathology within the Alzheimer's continuum is crucial to develop therapeutic and preventive strategies. The objective of this study is to test whether cognitively unimpaired individuals with a low burden of A beta pathology have a distinct CSF, structural, and functional neuroimaging biomarker profile. Methods: Cross-sectional study of 318 middle-aged, cognitively unimpaired individuals from the ALFA+ cohort. We measured CSF A beta 42/40, phosphorylated tau (p-tau), total tau (t-tau), neurofilament light (NfL), neurogranin, sTREM2, YKL40, GFAP, IL6, S100B, and alpha-synuclein. Participants also underwent cognitive assessments, APOE genotyping, structural MRI, [F-18]-FDG, and [F-18]-flutemetamol PET. To ensure the robustness of our results, we used three definitions of low burden of A beta pathology: (1) positive CSF A beta 42/40 and < 30 Centiloids in A beta PET, (2) positive CSF A beta 42/40 and negative A beta PET visual read, and (3) 20-40 Centiloid range in A beta PET. We tested CSF and neuroimaging biomarker differences between the low burden group and the corresponding A beta-negative group, adjusted by age and sex. Results: The prevalence and demographic characteristics of the low burden group differed between the three definitions. CSF p-tau and t-tau were increased in the low burden group compared to the A beta-negative in all definitions. CSF neurogranin was increased in the low burden group definitions 1 and 3, while CSF NfL was only increased in the low burden group definition 1. None of the defined low burden groups showed signs of atrophy or glucose hypometabolism. Instead, we found slight increases in cortical thickness and metabolism in definition 2. Conclusions: There are biologically meaningful A beta-downstream effects in individuals with a low burden of A beta pathology, while structural and functional changes are still subtle or absent. These findings support considering individuals with a low burden of A beta pathology for clinical trials.
|
|
| 10. |
- Mila-Aloma, M., et al.
(författare)
-
Comparative Analysis of Different Definitions of Amyloid-beta Positivity to Detect Early Downstream Pathophysiological Alterations in Preclinical Alzheimer
- 2021
-
Ingår i: Jpad-Journal of Prevention of Alzheimers Disease. - : SERDI. - 2274-5807. ; 8:1, s. 68-77
-
Tidskriftsartikel (refereegranskat)abstract
- Amyloid-beta (A beta) positivity is defined using different biomarkers and different criteria. Criteria used in symptomatic patients may conceal meaningful early A beta pathology in preclinical Alzheimer. Therefore, the description of sensitive cutoffs to study the pathophysiological changes in early stages of the Alzheimer'scontinuumis critical. Here, we compare different A beta classification approaches and we show their performance in detecting pathophysiological changes downstream A beta pathology. We studied 368 cognitively unimpaired individuals of the ALFA+ study, many of whom in the preclinical stage of the Alzheimer'scontinuum.Participants underwent A beta PET and CSF biomarkers assessment. We classified participants as A beta -positive using five approaches: (1) CSF A beta 42 < 1098 pg/ml; (2) CSF A beta 42/40 < 0.071; (3) A beta PET Centiloid > 12; (4) A beta PET Centiloid > 30 or (5) A beta PET Positive visual read. We assessed the correlations between A beta biomarkers and compared the prevalence of A beta positivity. We determined which approach significantly detected associations between A beta pathology and tau/neurodegeneration CSF biomarkers. We found that CSF-based approaches result in a higher A beta-positive prevalence than PET-based ones. There was a higher number of discordant participants classified as CSF A beta-positive but PET A beta-negative than CSF A beta-negative but PET A beta-positive. The CSF A beta 42/40 approach allowed optimal detection of significant associations with CSF p-tau and t-tau in the A beta-positive group. Altogether, we highlight the need for sensitive A beta -classifications to study the preclinical Alzheimer'scontinuumApproaches that define A beta positivity based on optimal discrimination of symptomatic Alzheimer's disease patients may be suboptimal for the detection of early pathophysiological alterations in preclinical Alzheimer.
|
|
