Neutrino oscillations: Entanglement, energy-momentum conservation and QFT

We consider several subtle aspects of the theory of neutrino oscillations which have been under discussion recently. We show that the $S$-matrix formalism of quantum field theory can adequately describe neutrino oscillations if correct physics conditions are imposed. This includes space-time localization of the neutrino production and detection processes. Space-time diagrams are introduced, which characterize this localization and illustrate the coherence issues of neutrino oscillations. We discuss two approaches to calculations of the transition amplitudes, which allow different physics interpretations: (i) using configuration-space wave packets for the involved particles, which leads to approximate conservation laws for their mean energies and momenta; (ii) calculating first a plane-wave amplitude of the process, which exhibits exact energy-momentum conservation, and then convoluting it with the momentum-space wave packets of the involved particles. We show that these two approaches are equivalent. Kinematic entanglement (which is invoked to ensure exact energy-momentum conservation in neutrino oscillations) and subsequent disentanglement of the neutrinos and recoiling states are in fact irrelevant when the wave packets are considered. We demonstrate that the contribution of the recoil particle to the oscillation phase is negligible provided that the coherence conditions for neutrino production and detection are satisfied. Unlike in the previous situation, the phases of both neutrinos from $Z^0$ decay are important, leading to a realization of the Einstein-Podolsky-Rosen paradox.Comment: 30 pages, 3 eps figures; presentation improved, clarifications added. To the memory of G.T. Zatsepi

Open Issues on the Synthesis of Evolved Stellar Populations at Ultraviolet Wavelengths

In this paper we briefly review three topics that have motivated our (and others') investigations in recent years within the context of evolutionary population synthesis techniques. These are: The origin of the FUV up-turn in elliptical galaxies, the age-metallicity degeneracy, and the study of the mid-UV rest-frame spectra of distant red galaxies. We summarize some of our results and present a very preliminary application of a UV grid of theoretical spectra in the analysis of integrated properties of aged stellar populations. At the end, we concisely suggest how these topics can be tackled once the World Space Observatory enters into operation in the midst of this decade.Comment: 8 pages, 4 figures, accepted for publication in Astrophysics & Space Science, UV Universe special issu

Palaeontology, the biogeohistory of Victoria

The broad-scale distribution of fossils within Victoria is controlled by general global patterns in the biological evolution of life on Earth, the local development and environmental evolution of habitats, and the occurrence of geological processes conducive to the preservation of fossil floras and faunas. Early Palaeozoic fossils are mostly marine in origin because of the predominance of marine sedimentary rocks in Victoria and because life on land was not significant during most of this time interval. Middle Palaeozoic sequences have both terrestrial and marine fossil records. Within Victoria, marine rocks are only very minor components of strata deposited during the late Palaeozoic, so that few marine fossils are known from this time period. A similar situation existed during most of the Mesozoic except towards the end of this era when marine conditions began to prevail in the Bass Strait region. During long intervals in the Cainozoic, large areas of Victoria were flooded by shallow-marine seas, particularly in the southern basins of Bass Strait, as well as in the northwest of the State (Murray Basin). Cainozoic sediments contain an extraordinary range of animal and plant fossils. During the Quaternary, the landscape of Victoria became, and continues to be, dominated by continental environments including, at times, extensive freshwater lake systems. Fossil floras and faunas from sediments deposited in these lake systems and from other continental sediments, as well as from Quaternary sediments deposited in marginal marine environments, collectively record a history of rapid fluctuations in climate and sea level.<br /

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc

Associations between DNA methylation and BMI vary by metabolic health status: a potential link to disparate cardiovascular outcomes

Background: Body mass index (BMI), a well-known risk factor for poor cardiovascular outcomes, is associated with differential DNA methylation (DNAm). Similarly, metabolic health has also been associated with changes in DNAm. It is unclear how overall metabolic health outside of BMI may modify the relationship between BMI and methylation profiles, and what consequences this may have on downstream cardiovascular disease. The purpose of this study was to identify cytosine-phosphate-guanine (CpG) sites at which the association between BMI and DNAm could be modified by overall metabolic health. Results: The discovery study population was derived from three Women’s Health Initiative (WHI) ancillary studies (n = 3977) and two Atherosclerosis Risk in Communities (ARIC) ancillary studies (n = 3520). Findings were validated in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (n = 1200). Generalized linear models regressed methylation β values on the interaction between BMI and metabolic health Z score (BMI × MHZ) adjusted for BMI, MHZ, cell composition, chip number and location, study characteristics, top three ancestry principal components, smoking, age, ethnicity (WHI), and sex (ARIC). Among the 429,566 sites examined, differential associations between BMI × MHZ and DNAm were identified at 22 CpG sites (FDR q < 0.05), with one site replicated in MESA (cg18989722, in the TRAPPC9 gene). Three of the 22 sites were associated with incident coronary heart disease (CHD) in WHI. For each 0.01 unit increase in DNAm β value, the risk of incident CHD increased by 9% in one site and decreased by 6–10% in two sites over 25 years. Conclusions: Differential associations between DNAm and BMI by MHZ were identified at 22 sites, one of which was validated (cg18989722) and three of which were predictive of incident CHD. These sites are located in several genes related to NF-kappa-B signaling, suggesting a potential role for inflammation between DNA methylation and BMI-associated metabolic health

The Polygenic and Monogenic Basis of Blood Traits and Diseases

Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation. Analysis of blood cell traits in the UK Biobank and other cohorts illuminates the full genetic architecture of hematopoietic phenotypes, with evidence supporting the omnigenic model for complex traits and linking polygenic burden with monogenic blood diseases

Clonal hematopoiesis associated with epigenetic aging and clinical outcomes

Clonal hematopoiesis of indeterminate potential (CHIP) is a common precursor state for blood cancers that most frequently occurs due to mutations in the DNA-methylation modifying enzymes DNMT3A or TET2. We used DNA-methylation array and whole-genome sequencing data from four cohorts together comprising 5522 persons to study the association between CHIP, epigenetic clocks, and health outcomes. CHIP was strongly associated with epigenetic age acceleration, defined as the residual after regressing epigenetic clock age on chronological age, in several clocks, ranging from 1.31 years (GrimAge, p &lt; 8.6 × 10−7) to 3.08 years (EEAA, p &lt; 3.7 × 10−18). Mutations in most CHIP genes except DNA-damage response genes were associated with increases in several measures of age acceleration. CHIP carriers with mutations in multiple genes had the largest increases in age acceleration and decrease in estimated telomere length. Finally, we found that ~40% of CHIP carriers had acceleration &gt;0 in both Hannum and GrimAge (referred to as AgeAccelHG+). This group was at high risk of all-cause mortality (hazard ratio 2.90, p &lt; 4.1 × 10−8) and coronary heart disease (CHD) (hazard ratio 3.24, p &lt; 9.3 × 10−6) compared to those who were CHIP−/AgeAccelHG−. In contrast, the other ~60% of CHIP carriers who were AgeAccelHG− were not at increased risk of these outcomes. In summary, CHIP is strongly linked to age acceleration in multiple clocks, and the combination of CHIP and epigenetic aging may be used to identify a population at high risk for adverse outcomes and who may be a target for clinical interventions

Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele