Neutrino oscillations and mixings with three flavors

Global fits to all data of candidates for neutrino oscillations are presented in the framework of a three-flavor model. The analysis excludes mass regions where the MSW effect is important for the solar neutrino problem. The best fit gives $\theta_1 \approx 28.9^\circ, \theta_2 \approx 4.2^\circ, \theta_3 - m_2^2 \approx 1.11 eV^2$ indicating essentially maximal mixing between the two lightest neutrino mass eigenstates

Decuplet Baryon Magnetic Moments in the Chiral Quark Model

We present calculations of the decuplet baryon magnetic moments in the chiral quark model. As input we use parameters obtained in qualitatively accurate fits to the octet baryon magnetic moments studied previously. The values found for the magnetic moments of $\Delta^{++}$ and $\Omega^{-}$ are in good agreement with experiments. We finally calculate the total quark spin polarizations of the decuplet baryons and find that they are considerably smaller than what is expected from the non-relativistic quark model

Biomarkers of brain injury in patients with stress-related exhaustion: A longitudinal study

INTRODUCTION: Exhaustion Disorder (ED) is a stress-induced disorder, characterized by extreme fatigue, cognitive impairments, and intolerance to stress. These symptoms can be long-lasting, suggesting that the long-term stress may have initiated pathophysiological processes in the brains of patients with ED. The aims of the study were I) to investigate if plasma levels of neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau (p-tau181) differ between patients with ED and healthy controls, and II) to investigate if these differences persist over time. METHOD: Plasma NfL, GFAP and p-tau181 were quantified in 150 patients with ED at the time of diagnosis (baseline), 149 patients at long-term follow-up (7-12 years later, median follow-up time 9 years and 5 months), and 100 healthy controls. RESULTS: Plasma levels of NfL and GFAP were significantly higher in the ED group at baseline compared with controls (mean difference of NfL 0.167, 95 % CI 0.055-0.279; mean difference of GFAP 0.132, 95 % CI 0.008-0.257), while p-tau181 did not differ between the groups. Plasma levels of NfL were significantly lower in the ED group at follow-up than in the same group at baseline (mean difference -0.115, 95 % CI -0.186-(-0.045)), while plasma levels of GFAP did not differ between the groups, and plasma levels of p-tau181 were significantly higher in the ED group at follow-up than in the same group at baseline (mean difference 0.083, 95 % CI 0.016-0.151). At follow-up, there were no significant differences between the ED group and the control group for any of the proteins. CONCLUSION: Plasma levels of NfL and GFAP were increased in patients with ED during the first months of the disease, indicative of axonal and glial pathophysiological processes, but had normalized at long-term follow-up

The effects of matter density uncertainties on neutrino oscillations in the Earth

We compare three different methods to evaluate uncertainties in the Earth's matter density profile, which are relevant to long baseline experiments, such as neutrino factories.Comment: 3 pages, 1 figure. Talk given at the NuFact'02 Workshop, London, 1-6 July, 200

Octet Baryon Magnetic Moments in the Chiral Quark Model with Configuration Mixing

The Coleman-Glashow sum-rule for magnetic moments is always fulfilled in the chiral quark model, independently of SU(3) symmetry breaking. This is due to the structure of the wave functions, coming from the non-relativistic quark model. Experimentally, the Coleman-Glashow sum-rule is violated by about ten standard deviations. To overcome this problem, two models of wave functions with configuration mixing are studied. One of these models violates the Coleman-Glashow sum-rule to the right degree and also reproduces the octet baryon magnetic moments rather accurately.Comment: 22 pages, RevTe

GRADE equity guidelines 4: guidance on how to assess and address health equity within the evidence to decision process

Objective: The aim of this paper is to provide detailed guidance on how to incorporate health equity within the GRADE (Grading Recommendations Assessment and Development Evidence) evidence to decision process. Study design and setting: We developed this guidance based on the GRADE evidence to decision (EtD) framework, iteratively reviewing and modifying draft documents, in person discussion of project group members and input from other GRADE members. Results: Considering the impact on health equity may be required, both in general guidelines, and guidelines that focus on disadvantaged populations. We suggest two approaches to incorporate equity considerations: 1) assessing the potential impact of interventions on equity and; 2) incorporating equity considerations when judging or weighing each of the evidence to decision criteria. We provide guidance and include illustrative examples. Conclusion: Guideline panels should consider the impact of recommendations on health equity with attention to remote and underserviced settings and disadvantaged populations. Guideline panels may wish to incorporate equity judgments across the evidence to decision framework

Associations of Fully Automated CSF and Novel Plasma Biomarkers With Alzheimer Disease Neuropathology at Autopsy

OBJECTIVE: To study cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) analyzed by fully automated Elecsys immunoassays in comparison to neuropathologic gold standards, and compare their accuracy to plasma phosphorylated tau (p-tau181) measured using a novel Simoa method. METHODS: We studied ante-mortem Elecsys-derived CSF biomarkers in 45 individuals who underwent standardized post-mortem assessments of AD and non-AD neuropathologic changes at autopsy. In a subset of 26 participants, we also analysed ante-mortem levels of plasma p-tau181 and neurofilament light (NfL). Reference biomarker values were obtained from 146 amyloid-PET-negative healthy controls (HC). RESULTS: All CSF biomarkers clearly distinguished pathology-confirmed AD dementia (N=27) from HC (AUCs=0.86-1.00). CSF total-tau (t-tau), p-tau181, and their ratios with Aβ1-42, also accurately distinguished pathology-confirmed AD from non-AD dementia (N=8; AUCs=0.94-0.97). In pathology-specific analyses, intermediate-to-high Thal amyloid phases were best detected by CSF Aβ1-42 (AUC[95% CI]=0.91[0.81-1]), while intermediate-to-high CERAD neuritic plaques and Braak tau stages were best detected by CSF p-tau181 (AUC=0.89[0.79-0.99] and 0.88[0.77-0.99], respectively). Optimal Elecsys biomarker cut-offs were derived at 1097/229/19 pg/ml for Aβ1-42, t-tau, and p-tau181. In the plasma subsample, both plasma p-tau181 (AUC=0.91[0.86-0.96]) and NfL (AUC=0.93[0.87-0.99]) accurately distinguished pathology-confirmed AD (N=14) from HC. However, only p-tau181 distinguished AD from non-AD dementia cases (N=4; AUC=0.96[0.88-1.00]), and showed a similar, though weaker, pathologic specificity for neuritic plaques (AUC=0.75[0.52-0.98]) and Braak stage (AUC=0.71[0.44-0.98]) as CSF p-tau181. CONCLUSIONS: Elecsys-derived CSF biomarkers detect AD neuropathologic changes with very high discriminative accuracy in-vivo. Preliminary findings support the use of plasma p-tau181 as an easily accessible and scalable biomarker of AD pathology. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that fully-automated CSF t-tau and p-tau181measurements discriminate between autopsy-confirmed Alzheimer's disease and other dementias

Biomarkers of brain injury in patients with stress-related exhaustion: A longitudinal study

Introduction: Exhaustion Disorder (ED) is a stress-induced disorder, characterized by extreme fatigue, cognitive impairments, and intolerance to stress. These symptoms can be long-lasting, suggesting that the long-term stress may have initiated pathophysiological processes in the brains of patients with ED. The aims of the study were I) to investigate if plasma levels of neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and phos-phorylated tau (p-tau181) differ between patients with ED and healthy controls, and II) to investigate if these differences persist over time.Method: Plasma NfL, GFAP and p-tau181 were quantified in 150 patients with ED at the time of diagnosis (baseline), 149 patients at long-term follow-up (7-12 years later, median follow-up time 9 years and 5 months), and 100 healthy controls.Results: Plasma levels of NfL and GFAP were significantly higher in the ED group at baseline compared with controls (mean difference of NfL 0.167, 95 % CI 0.055-0.279; mean difference of GFAP 0.132, 95 % CI 0.008-0.257), while p-tau181 did not differ between the groups. Plasma levels of NfL were significantly lower in the ED group at follow-up than in the same group at baseline (mean difference-0.115, 95 % CI - 0.186- (-0.045)), while plasma levels of GFAP did not differ between the groups, and plasma levels of p-tau181 were significantly higher in the ED group at follow-up than in the same group at baseline (mean difference 0.083, 95 % CI 0.016-0.151). At follow-up, there were no significant differences between the ED group and the control group for any of the proteins.Conclusion: Plasma levels of NfL and GFAP were increased in patients with ED during the first months of the disease, indicative of axonal and glial pathophysiological processes, but had normalized at long-term follow-up.</p

Time course of phosphorylated tau181 in blood across the Alzheimer's disease spectrum

Tau phosphorylated at threonine 181 (p-tau181) measured in blood plasma has recently been proposed as an accessible, scalable, and highly specific biomarker for Alzheimer’s disease. Longitudinal studies, however, investigating the temporal dynamics of this novel biomarker are lacking. It is therefore unclear when in the disease process plasma p-tau181 increases above physiological levels and how it relates to the spatiotemporal progression of Alzheimer’s disease-characteristic pathologies. We aimed to establish the natural time course of plasma p-tau181 across the sporadic Alzheimer’s disease spectrum in comparison to those of established imaging- and fluid-derived biomarkers of Alzheimer’s disease. We examined longitudinal data from a large prospective cohort of elderly individuals enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (n=1067) covering a wide clinical spectrum from normal cognition to dementia, and with measures of plasma p-tau181 and an [18F]florbetapir amyloid-β (Aβ) positron emission tomography (PET) scan at baseline. A subset of participants (n=864) also had measures of Aβ1-42 and p-tau181 levels in cerebrospinal fluid (CSF), and another subset (n=298) had undergone an [18F]flortaucipir tau PET scan six years later. We performed brain-wide analyses to investigate the associations of plasma p-tau181 baseline levels and longitudinal change with progression of regional Aβ pathology and tau burden six years later, and estimated the time course of changes in plasma p-tau181 and other Alzheimer’s disease biomarkers employing a previously developed method for the construction of long-term biomarker temporal trajectories using shorter-term longitudinal data. Spline regressions demonstrated that earliest plasma p-tau181 changes occurred even before Aβ-markers reached abnormal levels, with greater rates of change correlating with increased Aβ pathology. Voxel-wise PET analyses yielded relatively weak, yet significant, associations of plasma p-tau181 with Aβ pathology in early-accumulating brain regions in cognitively healthy individuals, while the strongest associations with Aβ were observed in late-accumulating regions in patients with mild cognitive impairment. Cross-sectional and particularly longitudinal measures of plasma p-tau181 were associated with widespread cortical tau aggregation six years later, covering temporo-parietal regions typical for neurofibrillary tangle distribution in Alzheimer’s disease. Finally, we estimated that plasma p-tau181 reaches abnormal levels approximately 6.5 and 5.7 years after CSF- and PET-measures of Aβ, respectively, following similar dynamics as CSF p-tau181. Our findings suggest that plasma p-tau181 increases are associated with the presence of widespread cortical Aβ pathology and with prospective Alzheimer’s disease-typical tau aggregation, providing clear implications for the use of this novel blood biomarker as a diagnostic and screening tool for Alzheimer’s disease