Scaling solutions as Early Dark Energy resolutions to the Hubble tension

A wide class of scalar field models including Quintessence and K-essence have the attractive property of tracker regimes, where the energy density stored in the field evolves so as to mimic that of the dominant background component. During this evolution, for a brief period of time, there is an increase in the energy density of the field as it spirals in towards its attractor solution. We show that when the peak of this energy density occurs around the epoch of equality, we can address a key requirement of early dark energy (EDE), postulated as a solution to the Hubble tension. In particular we demonstrate how this can occur in a wide class of Quintessence, axion and K-essence models, before showing that the Quintessence models suffer in that they generally lead to sound speeds incompatible with the requirements of EDE, whereas the K-essence and axion models can do a better job of fitting the data

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

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Use of single photon emission computed tomography and magnetic resonance to evaluate central nervous system involvement in patients with juvenile systemic lupus erythematosus

The objective of the present study was to identify the single photon emission computed tomography (SPECT) and magnetic resonance (MR) findings in juvenile systemic lupus erythematosus (JSLE) patients with CNS involvement and to try to correlate them with neurological clinical history data and neurological clinical examination. Nineteen patients with JSLE (16 girls and 3 boys, mean age at onset 9.2 years) were submitted to neurological examination, electroencephalography, cerebrospinal fluid analysis, SPECT and MR. All the evaluations were made separately within a period of 15 days. SPECT and MR findings were analyzed independently by two radiologists. Electroencephalography and cerebrospinal fluid analysis revealed no relevant alterations. Ten of 19 patients (53%) presented neurological abnormalities including present or past neurological clinical history (8/19, 42%), abnormal neurological clinical examination (5/19, 26%), and abnormal SPECT or MR (8/19, 42% and 3/19, 16%, respectively). The most common changes in SPECT were cerebral hypoperfusion and heterogeneous distribution of blood flow. The most common abnormalities in MR were leukomalacia and diffuse alterations of white matter. There was a correlation between SPECT and MR (P<0.05). We conclude that SPECT and MR are complementary and useful exams in the evaluation of neurological involvement of lupus

Notch Impact Behavior of Oxide Dispersion Strengthened (ODS) Fe20Cr5Al alloy

In this paper tensile tests and LS and LT notched Charpy impact tests were performed at the temperature range between -196 and 200 °C on an oxide dispersion strengthened (ODS) Fe20Cr6Al0.5Y2O3 hot-rolled tube. The absorbed energy values in the range of high-temperatures of LS notched specimens is considerably higher than those of LT notched specimens; however such values tend to converge as temperature increases. Ductile fracture on the normal planes to RD with delaminations parallel to the tube surface were observed in the temperature range between RT and 200 °C. Delaminations of crack divider type were observed in LT specimens, whereas delaminations of crack arrester type were observed in LS specimens. The yttria particles in the grain boundaries and the transverse plastic anisotropy are the possible causes of that the delaminations were parallel to the tube surfacePM 2000 is a trademark of Plansee GmbH. The authors acknowledge the financial support of the Spanish Ministerio de Economia e Innovacio´ n (MINECO) in the form of a Coordinate Project in the Energy Area of Plan Nacional 2009 (ENE2009-13766-C04-01). G.P. acknowledges MINECO for financial support in the form of PhD Research Grant (FPI). This research was supported by ORNL’s Shared Research Equipment (SHaRE) User Facility, which is sponsored by the Office of Basic Energy Sciences, U.S. Department of EnergyPeer reviewe

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease