421 research outputs found
The cognitive requirements for developing a multimodal communication system: Evidence from experimental semiotics and comparative cognition
Specifying the cognitive requirements for developing a structured, symbolic communication system is crucial when considering what made humans language-ready and enabled them to create language. It is equally important to understand to which extent these requirements are shared with other animals and how they evolved. Experimental semiotics elucidates the processes and necessary requirements for the emergence of a symbolic communication system in interaction. We take an evolutionary perspective to find out what cognitive abilities are essential for successful communication, and to what extent these cognitive abilities are present in animals. By conducting a meta-analysis of existing studies and comparing cognitive abilities across species, we identify common factors like theory of mind and categorical perception and highlight the similarities and differences in these abilities between humans and animals. This innovative approach provides valuable insights into the cognitive underpinnings of symbolic communication system emergence, contributing to our understanding of language evolution
Ab Initio No Core Shell Model - Recent Results and Further Prospects
There has been significant recent progress in solving the long-standing
problems of how nuclear shell structure and collective motion emerge from
underlying microscopic inter-nucleon interactions. We review a selection of
recent significant results within the ab initio No Core Shell Model (NCSM)
closely tied to three major factors enabling this progress: (1) improved
nuclear interactions that accurately describe the experimental two-nucleon and
three-nucleon interaction data; (2) advances in algorithms to simulate the
quantum many-body problem with strong interactions; and (3) continued rapid
development of high-performance computers now capable of performing floating point operations per second. We also comment on prospects for
further developments.Comment: Invited paper presented at NTSE-2014 and published online in the
proceedings (see footnote on p.1
Targeting hypoxia-inducible factor-1α (HIF-1α) in combination with antiangiogenic therapy: a phase I trial of bortezomib plus bevacizumab.
PurposeWe hypothesized that bortezomib, an agent that suppresses HIF-1α transcriptional activity, when combined with bevacizumab, would obviate the HIF-1α resistance pathway. The objectives of this phase I trial were to assess safety and biological activity of this combination.Experimental designPatients with advanced, refractory malignancies were eligible. Patients received bevacizumab and bortezomib (3-week cycle) with dose expansions permitted if responses were seen and for assessing correlates. Pharmacodynamic assessment included plasma VEGF, VEGFR2, 20S proteasome inhibition, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and HIF-1α tumor expression.ResultsNinety-one patients were treated (median=6 prior treatments). The FDA-approved doses of both drugs were safely reached, and the recommended phase 2 dose (RP2D) is bevacizumab 15 mg/kg with bortezomib 1.3 mg/m(2). Four patients attained partial response (PR) and seven patients achieved stable disease (SD) ≥ 6 months (Total SD ≥ 6 months/PR=11 (12%)). The most common drug-related toxicities included thrombocytopenia (23%) and fatigue (19%). DCE-MRI analysis demonstrated no dose-dependent decreases in K(trans) although analysis was limited by small sample size (N=12).ConclusionCombination bevacizumab and bortezomib is well-tolerated and has demonstrated clinical activity in patients with previously treated advanced malignancy. Pharmacodynamic assessment suggests that inhibition of angiogenic activity was achieved
SWIPE: a bolometric polarimeter for the Large-Scale Polarization Explorer
The balloon-borne LSPE mission is optimized to measure the linear
polarization of the Cosmic Microwave Background at large angular scales. The
Short Wavelength Instrument for the Polarization Explorer (SWIPE) is composed
of 3 arrays of multi-mode bolometers cooled at 0.3K, with optical components
and filters cryogenically cooled below 4K to reduce the background on the
detectors. Polarimetry is achieved by means of large rotating half-wave plates
and wire-grid polarizers in front of the arrays. The polarization modulator is
the first component of the optical chain, reducing significantly the effect of
instrumental polarization. In SWIPE we trade angular resolution for
sensitivity. The diameter of the entrance pupil of the refractive telescope is
45 cm, while the field optics is optimized to collect tens of modes for each
detector, thus boosting the absorbed power. This approach results in a FWHM
resolution of 1.8, 1.5, 1.2 degrees at 95, 145, 245 GHz respectively. The
expected performance of the three channels is limited by photon noise,
resulting in a final sensitivity around 0.1-0.2 uK per beam, for a 13 days
survey covering 25% of the sky.Comment: In press. Copyright 2012 Society of Photo-Optical Instrumentation
Engineers. One print or electronic copy may be made for personal use only.
Systematic reproduction and distribution, duplication of any material in this
paper for a fee or for commercial purposes, or modification of the content of
the paper are prohibite
Reforms in Metro Manila's bus transport system hastened by the Covid-19 pandemic: A policy capacity analysis of the EDSA busway
In response to the health and mobility issues caused by the Covid-19 pandemic, the Philippine government took advantage of opportunities to expedite public transport reforms by converting a portion of Epifanio delos Santos Avenue (EDSA), Metro Manila's busiest thoroughfare, into a dedicated busway. This deserves a closer look since historically, solutions catering to EDSA have been bereft with challenges given the overlapping powers of various authorities and multitude of interests that benefit from the status-quo. Through semi-structured interviews with key actors followed by a policy capacity analysis, the authors found that the pandemic provided opportunities for the key institutions to gain political legitimacy and authority that pushed its stakeholders to cooperate. However, this new solution forced them to take on tasks that are outside their regular responsibilities so while they were able to provide measures to make EDSA Busway succeed in the short-term, much work needs to be done to sustain the gains achieved
The Large-Scale Polarization Explorer (LSPE)
The LSPE is a balloon-borne mission aimed at measuring the polarization of
the Cosmic Microwave Background (CMB) at large angular scales, and in
particular to constrain the curl component of CMB polarization (B-modes)
produced by tensor perturbations generated during cosmic inflation, in the very
early universe. Its primary target is to improve the limit on the ratio of
tensor to scalar perturbations amplitudes down to r = 0.03, at 99.7%
confidence. A second target is to produce wide maps of foreground polarization
generated in our Galaxy by synchrotron emission and interstellar dust emission.
These will be important to map Galactic magnetic fields and to study the
properties of ionized gas and of diffuse interstellar dust in our Galaxy. The
mission is optimized for large angular scales, with coarse angular resolution
(around 1.5 degrees FWHM), and wide sky coverage (25% of the sky). The payload
will fly in a circumpolar long duration balloon mission during the polar night.
Using the Earth as a giant solar shield, the instrument will spin in azimuth,
observing a large fraction of the northern sky. The payload will host two
instruments. An array of coherent polarimeters using cryogenic HEMT amplifiers
will survey the sky at 43 and 90 GHz. An array of bolometric polarimeters,
using large throughput multi-mode bolometers and rotating Half Wave Plates
(HWP), will survey the same sky region in three bands at 95, 145 and 245 GHz.
The wide frequency coverage will allow optimal control of the polarized
foregrounds, with comparable angular resolution at all frequencies.Comment: In press. Copyright 2012 Society of Photo-Optical Instrumentation
Engineers. One print or electronic copy may be made for personal use only.
Systematic reproduction and distribution, duplication of any material in this
paper for a fee or for commercial purposes, or modification of the content of
the paper are prohibite
Automated multi-subject fiber clustering of mouse brain using dominant sets
Mapping of structural and functional connectivity may provide deeper understanding of brain function and disfunction. Diffusion Magnetic Resonance Imaging (DMRI) is a powerful technique to non-invasively delineate white matter (WM) tracts and to obtain a three-dimensional description of the structural architecture of the brain. However, DMRI tractography methods produce highly multi-dimensional datasets whose interpretation requires advanced analytical tools. Indeed, manual identification of specific neuroanatomical tracts based on prior anatomical knowledge is time-consuming and prone to operator-induced bias. Here we propose an automatic multi-subject fiber clustering method that enables retrieval of group-wise WM fiber bundles. In order to account for variance across subjects, we developed a multi-subject approach based on a method known as Dominant Sets algorithm, via an intra- and cross-subject clustering. The intra-subject step allows us to reduce the complexity of the raw tractography data, thus obtaining homogeneous neuroanatomically-plausible bundles in each diffusion space. The cross-subject step, characterized by a proper space-invariant metric in the original diffusion space, enables the identification of the same WM bundles across multiple subjects without any prior neuroanatomical knowledge. Quantitative analysis was conducted comparing our algorithm with spectral clustering and affinity propagation methods on synthetic dataset. We also performed qualitative analysis on mouse brain tractography retrieving significant WM structures. The approach serves the final goal of detecting WM bundles at a population level, thus paving the way to the study of the WM organization across groups.Mapping of structural and functional connectivity may provide deeper understanding of brain function and disfunction. Diffusion Magnetic Resonance Imaging (DMRI) is a powerful technique to non-invasively delineate white matter (WM) tracts and to obtain a three-dimensional description of the structural architecture of the brain. However, DMRI tractography methods produce highly multi-dimensional datasets whose interpretation requires advanced analytical tools. Indeed, manual identification of specific neuroanatomical tracts based on prior anatomical knowledge is time-consuming and prone to operator-induced bias. Here we propose an automatic multi-subject fiber clustering method that enables retrieval of group-wise WM fiber bundles. In order to account for variance across subjects, we developed a multi-subject approach based on a method known as Dominant Sets algorithm, via an intra-and cross-subject clustering. The intra-subject step allows us to reduce the complexity of the raw tractography data, thus obtaining homogeneous neuroanatomically-plausible bundles in each diffusion space. The cross-subject step, characterized by a proper space-invariant metric in the original diffusion space, enables the identification of the same WM bundles across multiple subjects without any prior neuroanatomical knowledge. Quantitative analysis was conducted comparing our algorithm with spectral clustering and affinity propagation methods on synthetic dataset. We also performed qualitative analysis on mouse brain tractography retrieving significant WM structures. The approach serves the final goal of detecting WM bundles at a population level, thus paving the way to the study of the WM organization across groups
No Core CI calculations for light nuclei with chiral 2- and 3-body forces
The atomic nucleus is a self-bound system of strongly interacting nucleons. In No-Core Configuration Interaction calculations, the nuclear wavefunction is expanded in Slater determinants of single-nucleon wavefunctions (Configurations), and the many-body Schrödinger equation becomes a large sparse matrix problem. The challenge is to reach numerical convergence to within quantified numerical uncertainties for physical observables using finite truncations of the infinite-dimensional basis space. We discuss strategies for constructing and solving the resulting large sparse matrices for a set of low-lying eigenvalues and eigenvectors on current multicore computer architectures. Several of these strategies have been implemented in the code MFDn, a hybrid MPI/OpenMP Fortran code for ab initio nuclear structure calculations that scales well to over 200,000 cores. We discuss how the similarity renormalization group can be used to improve the numerical convergence. We present results for excitation energies and other selected observables for ⁸Be and ¹²C using realistic 2- and 3-body forces obtained from chiral perturbation theory. Finally, we demonstrate that collective phenomena such as rotational band structures can emerge from these microscopic calculations
Epigenetics, heritability and longitudinal analysis
© 2018 The Author(s). Background: Longitudinal data and repeated measurements in epigenome-wide association studies (EWAS) provide a rich resource for understanding epigenetics. We summarize 7 analytical approaches to the GAW20 data sets that addressed challenges and potential applications of phenotypic and epigenetic data. All contributions used the GAW20 real data set and employed either linear mixed effect (LME) models or marginal models through generalized estimating equations (GEE). These contributions were subdivided into 3 categories: (a) quality control (QC) methods for DNA methylation data; (b) heritability estimates pretreatment and posttreatment with fenofibrate; and (c) impact of drug response pretreatment and posttreatment with fenofibrate on DNA methylation and blood lipids. Results: Two contributions addressed QC and identified large statistical differences with pretreatment and posttreatment DNA methylation, possibly a result of batch effects. Two contributions compared epigenome-wide heritability estimates pretreatment and posttreatment, with one employing a Bayesian LME and the other using a variance-component LME. Density curves comparing these studies indicated these heritability estimates were similar. Another contribution used a variance-component LME to depict the proportion of heritability resulting from a genetic and shared environment. By including environmental exposures as random effects, the authors found heritability estimates became more stable but not significantly different. Two contributions investigated treatment response. One estimated drug-associated methylation effects on triglyceride levels as the response, and identified 11 significant cytosine-phosphate-guanine (CpG) sites with or without adjusting for high-density lipoprotein. The second contribution performed weighted gene coexpression network analysis and identified 6 significant modules of at least 30 CpG sites, including 3 modules with topological differences pretreatment and posttreatment. Conclusions: Four conclusions from this GAW20 working group are: (a) QC measures are an important consideration for EWAS studies that are investigating multiple time points or repeated measurements; (b) application of heritability estimates between time points for individual CpG sites is a useful QC measure for DNA methylation studies; (c) drug intervention demonstrated strong epigenome-wide DNA methylation patterns across the 2 time points; and (d) new statistical methods are required to account for the environmental contributions of DNA methylation across time. These contributions demonstrate numerous opportunities exist for the analysis of longitudinal data in future epigenetic studies
Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis
BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London
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