2,156 research outputs found
Predictors of response to pharmacological treatments in treatment-resistant schizophrenia - A systematic review and meta-analysis
Background: As the burden of treatment-resistant schizophrenia (TRS) on patients and society is high it is important to identify predictors of response to medications in TRS. The aim was to analyse whether baseline patient and study characteristics predict treatment response in TRS in drug trials. Methods: A comprehensive search strategy completed in PubMed, Cochrane and Web of Science helped identify relevant studies. The studies had to meet the following criteria: English language clinical trial of pharmacological treatment of TRS, clear definition of TRS and response, percentage of response reported, at least one baseline characteristic presented, and total sample size of at least 15. Meta-regression techniques served to explore whether baseline characteristics predict response to medication in TRS. Results: 77 articles were included in the systematic review. The overall sample included 7546 patients, of which 41% achieved response. Higher positive symptom score at baseline predicted higher response percentage. None of the other baseline patient or study characteristics achieved statistical significance at predicting response. When analysed in groups divided by antipsychotic drugs, studies of clozapine and other atypical antipsychotics produced the highest response rate. Conclusions: This meta-analytic review identified surprisingly few baseline characteristics that predicted treatment response. However, higher positive symptoms and the use of atypical antipsychotics - particularly clozapine -was associated with the greatest likelihood of response. The difficulty involved in the prediction of medication response in TRS necessitates careful monitoring and personalised medication management. There is a need for more investigations of the predictors of treatment response in TRS.Peer reviewe
Alpha, Betti and the Megaparsec Universe: on the Topology of the Cosmic Web
We study the topology of the Megaparsec Cosmic Web in terms of the
scale-dependent Betti numbers, which formalize the topological information
content of the cosmic mass distribution. While the Betti numbers do not fully
quantify topology, they extend the information beyond conventional cosmological
studies of topology in terms of genus and Euler characteristic. The richer
information content of Betti numbers goes along the availability of fast
algorithms to compute them.
For continuous density fields, we determine the scale-dependence of Betti
numbers by invoking the cosmologically familiar filtration of sublevel or
superlevel sets defined by density thresholds. For the discrete galaxy
distribution, however, the analysis is based on the alpha shapes of the
particles. These simplicial complexes constitute an ordered sequence of nested
subsets of the Delaunay tessellation, a filtration defined by the scale
parameter, . As they are homotopy equivalent to the sublevel sets of
the distance field, they are an excellent tool for assessing the topological
structure of a discrete point distribution. In order to develop an intuitive
understanding for the behavior of Betti numbers as a function of , and
their relation to the morphological patterns in the Cosmic Web, we first study
them within the context of simple heuristic Voronoi clustering models.
Subsequently, we address the topology of structures emerging in the standard
LCDM scenario and in cosmological scenarios with alternative dark energy
content. The evolution and scale-dependence of the Betti numbers is shown to
reflect the hierarchical evolution of the Cosmic Web and yields a promising
measure of cosmological parameters. We also discuss the expected Betti numbers
as a function of the density threshold for superlevel sets of a Gaussian random
field.Comment: 42 pages, 14 figure
G-structures and Domain Walls in Heterotic Theories
We consider heterotic string solutions based on a warped product of a
four-dimensional domain wall and a six-dimensional internal manifold,
preserving two supercharges. The constraints on the internal manifolds with
SU(3) structure are derived. They are found to be generalized half-flat
manifolds with a particular pattern of torsion classes and they include
half-flat manifolds and Strominger's complex non-Kahler manifolds as special
cases. We also verify that previous heterotic compactifications on half-flat
mirror manifolds are based on this class of solutions.Comment: 29 pages, reference added, typos correcte
Football players do not show "neural efficiency" in cortical activity related to visuospatial information processing during football scenes: an EEG mapping study
This study tested the hypothesis of cortical neural efficiency (i.e., reduced brain activation in experts) in the visuospatial information processing related to football (soccer) scenes in football players. Electroencephalographic data were recorded from 56 scalp electrodes in 13 football players and eight matched non-players during the observation of 70 videos with football actions lasting 2.5 s each. During these videos, the central fixation target changed color from red to blue or vice versa. The videos were watched two times. One time, the subjects were asked to estimate the distance between players during each action (FOOTBALL condition, visuospatial). Another time, they had to estimate if the fixation target was colored for a longer time in red or blue color (CONTROL condition, non-visuospatial). The order of the two conditions was pseudo-randomized across the subjects. Cortical activity was estimated as the percent reduction in power of scalp alpha rhythms (about 8-12 Hz) during the videos compared with a pre-video baseline (event-related desynchronization, ERD). In the FOOTBALL condition, a prominent and bilateral parietal alpha ERD (i.e., cortical activation) was greater in the football players than non-players (p < 0.05) in contrast with the neural efficiency hypothesis. In the CONTROL condition, no significant alpha ERD difference was observed. No difference in behavioral response time and accuracy was found between the two groups in any condition. In conclusion, a prominent parietal cortical activity related to visuospatial processes during football scenes was greater in the football players over controls in contrast with the neural efficiency hypothesis
Meteorological predictions for Mars 2020 Perseverance rover landing site at Jezero crater
Correction to: Space Sci Rev (2020) 216:148 https://doi.org/10.1007/s11214-020-00763-xPeer reviewe
Astrocytic Ion Dynamics: Implications for Potassium Buffering and Liquid Flow
We review modeling of astrocyte ion dynamics with a specific focus on the
implications of so-called spatial potassium buffering, where excess potassium
in the extracellular space (ECS) is transported away to prevent pathological
neural spiking. The recently introduced Kirchoff-Nernst-Planck (KNP) scheme for
modeling ion dynamics in astrocytes (and brain tissue in general) is outlined
and used to study such spatial buffering. We next describe how the ion dynamics
of astrocytes may regulate microscopic liquid flow by osmotic effects and how
such microscopic flow can be linked to whole-brain macroscopic flow. We thus
include the key elements in a putative multiscale theory with astrocytes
linking neural activity on a microscopic scale to macroscopic fluid flow.Comment: 27 pages, 7 figure
Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.
Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition
New results for the SQCD Hilbert series
We derive new explicit results for the Hilbert series of N=1 supersymmetric
QCD with U(N_c) and SU(N_c) color symmetry. We use two methods which have
previously been applied to similar computational problems in the analysis of
decay of unstable D-branes: expansions using Schur polynomials, and the log-gas
approach related to random matrix theory.Comment: 33 pages, 2 figures; v2: references and comments on the 3rd order
phase transition added; v3: refs. correcte
Systemic Blockade of Clever-1 Elicits Lymphocyte Activation Alongside Checkpoint Molecule Downregulation in Patients with Solid Tumors : Results from a Phase I/II Clinical Trial
Purpose: Macrophages are critical in driving an immunosuppressive tumor microenvironment that counteracts the efficacy of T-cell-targeting therapies. Thus, agents able to reprogram macrophages toward a proinflammatory state hold promise as novel immunotherapies for solid cancers. Inhibition of the macrophage scavenger receptor Clever-1 has shown benefit in inducing CD8 T-cell-mediated antitumor responses in mouse models of cancer, which supports the clinical development of Clever-1-targeting antibodies for cancer treatment. Patients and Methods: In this study, we analyzed the mode of action of a humanized IgG4 anti-Clever-1 antibody, FP-1305 (bexmarilimab), both in vitro and in patients with heavily pretreated metastatic cancer (n = 30) participating in part 1 (dose-finding) of a phase I/II open-label trial (NCT03733990). We studied the Clever-1 interactome in primary human macrophages in antibody pull-down assays and utilized mass cytometry, RNA sequencing, and cytokine profiling to evaluate FP-1305-induced systemic immune activation in patients with cancer. Results: Our pull-down assays and functional studies indicated that FP-1305 impaired multiprotein vacuolar ATPase-mediated endosomal acidification and improved the ability of macrophages to activate CD8(+)T-cells. In patients with cancer, FP-1305 administration led to suppression of nuclear lipid signaling pathways and a proinflammatory phenotypic switch in blood monocytes. These effects were accompanied by a significant increase and activation of peripheral T-cells with indications of antitumor responses in some patients. Conclusions: Our results reveal a nonredundant role played by the receptor Clever-1 in suppressing adaptive immune cells in humans. We provide evidence that targeting macrophage scavenging activity can promote an immune switch, potentially leading to intratumoral proinflammatory responses in patients with metastatic cancer.Peer reviewe
How Close Do We Live to Water? A Global Analysis of Population Distance to Freshwater Bodies
Traditionally, people have inhabited places with ready access to fresh water.
Today, over 50% of the global population lives in urban areas, and water
can be directed via tens of kilometres of pipelines. Still, however, a large
part of the world's population is directly dependent on access to natural
freshwater sources. So how are inhabited places related to the location of
freshwater bodies today? We present a high-resolution global analysis of how
close present-day populations live to surface freshwater. We aim to increase the
understanding of the relationship between inhabited places, distance to surface
freshwater bodies, and climatic characteristics in different climate zones and
administrative regions. Our results show that over 50% of the
world's population lives closer than 3 km to a surface freshwater body, and
only 10% of the population lives further than 10 km away. There are,
however, remarkable differences between administrative regions and climatic
zones. Populations in Australia, Asia, and Europe live closest to water.
Although populations in arid zones live furthest away from freshwater bodies in
absolute terms, relatively speaking they live closest to water considering the
limited number of freshwater bodies in those areas. Population distributions in
arid zones show statistically significant relationships with a combination of
climatic factors and distance to water, whilst in other zones there is no
statistically significant relationship with distance to water. Global studies on
development and climate adaptation can benefit from an improved understanding of
these relationships between human populations and the distance to fresh
water
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