6,376 research outputs found
Desegregation and Parental Choice in Public Schooling: A Legal Analysis of Controlled Choice Student Assignment Plans
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Use of functional imaging across clinical phases in CNS drug development
The use of novel brain biomarkers using nuclear magnetic resonance imaging holds potential of making central nervous system (CNS) drug development more efficient. By evaluating changes in brain function in the disease state or drug effects on brain function, the technology opens up the possibility of obtaining objective data on drug effects in the living awake brain. By providing objective data, imaging may improve the probability of success of identifying useful drugs to treat CNS diseases across all clinical phases (I–IV) of drug development. The evolution of functional imaging and the promise it holds to contribute to drug development will require the development of standards (including good imaging practice), but, if well integrated into drug development, functional imaging can define markers of CNS penetration, drug dosing and target engagement (even for drugs that are not amenable to positron emission tomography imaging) in phase I; differentiate objective measures of efficacy and side effects and responders vs non-responders in phase II, evaluate differences between placebo and drug in phase III trials and provide insights into disease modification in phase IV trials
Nonergodic behavior of the clean Bose-Hubbard chain
We study ergodicity breaking in the clean Bose-Hubbard chain for small
hopping strength. We see the existence of a non-ergodic regime by means of
indicators as the half-chain entanglement entropy of the eigenstates, the
average level spacing ratio, {the properties of the eigenstate-expectation
distribution of the correlation and the scaling of the Inverse Participation
Ratio averages.} We find that this ergodicity breaking {is different from
many-body localization} because the average half-chain entanglement entropy of
the eigenstates obeys volume law. This ergodicity breaking appears unrelated to
the spectrum being organized in quasidegenerate multiplets at small hopping and
finite system sizes, so in principle it can survive also for larger system
sizes. We find that some imbalance oscillations in time which could mark the
existence of a glassy behaviour in space are well described by the dynamics of
a single symmetry-breaking doublet and {quantitatively} captured by a
perturbative effective XXZ model. We show that the amplitude of these
oscillations vanishes in the large-size limit. {Our findings are numerically
obtained for systems with . Extrapolations of our scalings to larger
system sizes should be taken with care, as discussed in the paper.Comment: 18 pages, 13 figures, extensively revised version published in
Physical Review B, Eq. (21) in the correct for
Gut microbiota and health: connecting actors across the metabolic system
Overweight-related metabolic diseases are an important threat to health in the Western world. Dietary habits are one of the main causative factors for metabolic syndrome, CVD and type 2 diabetes. The human gut microbiota is emerging as an important player in the interaction between diet and metabolic health. Gut microbial communities contribute to human metabolism through fermentation of dietary fibre and the result of intestinal saccharolytic fermentation is production of SCFA. Acetate, propionate and butyrate positively influence satiety, endocrine system, glucose homeostasis, adipogenesis, lipid oxidation, thermoregulation, hepatic gluconeogenesis, endothelial function and gut barrier integrity, and these mechanisms have all been linked to protection from type 2 diabetes, hypertension and cardiovascular health. The gut microbiota is also involved in bile acid metabolism and regulating their cell signalling potential, which has also been shown to modify pathways involved in metabolic health. Similarly, the gut microbiota renders recalcitrant plant polyphenols into biologically active small phenolic compounds which then act systemically to reduce metabolic disease risk. This review summarises how dietary patterns, specific foods and a healthy lifestyle may modulate metabolic health through the gut microbiota and their molecular cross-talk with the host
The Relationship Antecedents of Smoking (RAS) Scale: A new scale to assess couple-focused triggers to smoke.
The purpose of this pilot study is to assess the reliability and construct validity of a measure of relationship-focused antecedents for smoking (RAS). The scale includes both positively-valenced items (e.g.. “I feel like smoking when I am relaxing with my partner”) and negatively-valenced items (e.g., “I feel like smoking when my partner criticizes me”). Participants included 123 individuals who smoke cigarettes with co-habitating smoking (n=63) or non-smoking (n=60) romantic partners. Participants completed the RAS and a series of measures associated with smoking outcomes. Principal component analysis with varimax rotation resulted in a 2-component solution. The RAS showed excellent internal consistency for the total scale (α=.96) and for the positive (α=.88) and negative (α=.97) subscales. Higher positive subscale scores were associated with lower motivation to quit while higher negative scores were associated with lower relationship satisfaction and dyadic efficacy to quit. Higher scores on both subscales were related to higher social motives, dependence motives, and social outcome expectances. Participants with smoking partners reported higher positive subscale scores and lower negative subscale scores. The RAS may be helpful in the design of smoking cessation interventions for couples
Does the routine histological examination of the inferior mesenteric artery lymph nodes have a prognostic value in elderly patients with sigmoid colon and rectum tumors?
Spin-polarized oxygen hole states in cation deficient La(1-x)CaxMnO(3+delta)
When holes are doped into a Mott-Hubbard type insulator, like lightly doped
manganites of the La(1-x)CaxMnO3 family, the cooperative Jahn-Teller
distortions and the appearance of orbital ordering require an arrangement of
Mn(3+)/Mn(4+) for the establishment of the insulating canted antiferromagnetic
(for x<=0.1), or of the insulating ferromagnetic (for 0.1<x<= 0.2) ground
state. In the present work we provide NMR evidence about a novel and at the
same time puzzling effect in La(1-x)CaxMnO(3+delta) systems with cation
deficience. We show that in the low Ca-doping regime, these systems exhibit a
very strong hyperfine field at certain La nuclear sites, which is not present
in the stoichiometric compounds. Comparison of our NMR results with recent
x-ray absorption data at the Mn K edge, suggests the formation of a
spin-polarized hole arrangement on the 2p oxygen orbitals as the origin of this
effect.Comment: 10 pages, 4 Figures, submitted to PR
Definition of Naturally Processed Peptides Reveals Convergent Presentation of Autoantigenic Topoisomerase I Epitopes in Scleroderma.
ObjectiveAutoimmune responses to DNA topoisomerase I (topo I) are found in a subset of scleroderma patients who are at high risk for interstitial lung disease (ILD) and mortality. Anti-topo I antibodies (ATAs) are associated with specific HLA-DRB1 alleles, and the frequency of HLA-DR-restricted topo I-specific CD4+ T cells is associated with the presence, severity, and progression of ILD. Although this strongly implicates the presentation of topo I peptides by HLA-DR in scleroderma pathogenesis, the processing and presentation of topo I has not been studied.MethodsWe developed a natural antigen processing assay (NAPA) to identify putative CD4+ T cell epitopes of topo I presented by monocyte-derived dendritic cells (mo-DCs) from 6 ATA-positive patients with scleroderma. Mo-DCs were pulsed with topo I protein, HLA-DR-peptide complexes were isolated, and eluted peptides were analyzed by mass spectrometry. We then examined the ability of these naturally presented peptides to induce CD4+ T cell activation in 11 ATA-positive and 11 ATA-negative scleroderma patients.ResultsWe found that a common set of 10 topo I epitopes was presented by Mo-DCs from scleroderma patients with diverse HLA-DR variants. Sequence analysis revealed shared peptide-binding motifs within the HLA-DRβ chains of ATA-positive patients and a subset of topo I epitopes with distinct sets of anchor residues capable of binding to multiple different HLA-DR variants. The NAPA-derived epitopes elicited robust CD4+ T cell responses in 73% of ATA-positive patients (8 of 11), and the number of epitopes recognized correlated with ILD severity (P = 0.025).ConclusionThese findings mechanistically implicate the presentation of a convergent set of topo I epitopes in the development of scleroderma
Neuroimaging revolutionizes therapeutic approaches to chronic pain
An understanding of how the brain changes in chronic pain or responds to pharmacological or other therapeutic interventions has been significantly changed as a result of developments in neuroimaging of the CNS. These developments have occurred in 3 domains : (1) Anatomical Imaging which has demonstrated changes in brain volume in chronic pain; (2) Functional Imaging (fMRI) that has demonstrated an altered state in the brain in chronic pain conditions including back pain, neuropathic pain, and complex regional pain syndromes. In addition the response of the brain to drugs has provided new insights into how these may modify normal and abnormal circuits (phMRI or pharmacological MRI); (3) Chemical Imaging (Magnetic Resonance Spectroscopy or MRS) has helped our understanding of measures of chemical changes in chronic pain. Taken together these three domains have already changed the way in which we think of pain – it should now be considered an altered brain state in which there may be altered functional connections or systems and a state that has components of degenerative aspects of the CNS
A review on slurry bioreactors for bioremediation of soils and sediments
The aim of this work is to present a critical review on slurry bioreactors (SB) and their application to bioremediation of soils and sediments polluted with recalcitrant and toxic compounds. The scope of the review encompasses the following subjects: (i) process fundamentals of SB and analysis of advantages and disadvantages; (ii) the most recent applications of SB to laboratory scale and commercial scale soil bioremediation, with a focus on pesticides, explosives, polynuclear aromatic hydrocarbons, and chlorinated organic pollutants; (iii) trends on the use of surfactants to improve availability of contaminants and supplementation with degradable carbon sources to enhance cometabolism of pollutants; (iv) recent findings on the utilization of electron acceptors other than oxygen; (v) bioaugmentation and advances made on characterization of microbial communities of SB; (vi) developments on ecotoxicity assays aimed at evaluating bioremediation efficiency of the process
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