298 research outputs found
Using Movies to Probe the Neurobiology of Anxiety
Over the past century, research has helped us build a fundamental understanding of the neurobiological underpinnings of anxiety. Specifically, anxiety engages a broad range of cortico-subcortical neural circuitry. Core to this is a âdefensive response networkâ which includes an amygdala-prefrontal circuit that is hypothesized to drive attentional amplification of threat-relevant stimuli in the environment. In order to help prepare the body for defensive behaviors to threat, anxiety also engages peripheral physiological systems. However, our theoretical frameworks of the neurobiology of anxiety are built mostly on the foundations of tightly-controlled experiments, such as task-based fMRI. Whether these findings generalize to more naturalistic settings is unknown. To address this shortcoming, movie-watching paradigms offer an effective tool at the intersection of tightly controlled and entirely naturalistic experiments. Particularly, using suspenseful movies presents a novel and effective means to induce and study anxiety. In this thesis, I demonstrate the potential of movie-watching paradigms in the study of how trait and state anxiety impact the âdefensive response networkâ in the brain, as well as peripheral physiology. The key findings reveal that trait anxiety is associated with differing amygdala-prefrontal responses to suspenseful movies; specific trait anxiety symptoms are linked to altered states of anxiety during suspenseful movies; and states of anxiety during movies impact brain-body communication. Notably, my results frequently diverged from those of conventional task-based experiments. Taken together, the insights gathered from this thesis underscore the utility of movie-watching paradigms for a more nuanced understanding of how anxiety impacts the brain and peripheral physiology. These outcomes provide compelling evidence that further integration of naturalistic methods will be beneficial in the study of the neurobiology of anxiety
ActuEating: Designing, Studying and Exploring Actuating Decorative Artefacts
Actuating, dynamic materials offer substantial potential to enhance interior designs but there are currently few examples of how they might be utilised or impact user experiences. As part of a design-led exploration, we have prototyped (Wizard-of-Oz) an actuating, dining table runner (ActuEater1), and then developed a fully-interactive fabric version that both changes shape and colour (ActuEater2). Four in-situ deployments of âActuEatersâ in different dinner settings and subsequent âdesign critsâ showed insights into how people perceive, interpret and interact with such slow-technology in interesting (and often unexpected) ways. The results of our âActuEatingâ studies provide evidence for how an actuating artefact can be simultaneously a resource for social engagement and an interactive decorative. In response, we explore design opportunities for situating novel interactive materials in everyday settings, taking the leap into a new generation of interactive spaces, and critically considering new aesthetic possibilities
Immuno-virological discordance and the risk of non-AIDS and AIDS events in a large observational cohort of HIV-patients in Europe
The impact of immunosuppression despite virological suppression (immuno-virological discordance, ID) on the risk of developing fatal and non-fatal AIDS/non-AIDS events is unclear and remains to be elucidated. METHODS: Patients in EuroSIDA starting at least 1 new antiretroviral drug with CD4500 copies/mL were followed-up from the first day of VLgrade 3), cardio- and cerebrovascular events, and end-stage renal disease. Patients were classified over time according to whether current CD4 count was above (non-ID) or below (ID) baseline level. Relative rates (RR) of events were calculated for ID vs. non-ID using adjusted Poisson regression models. RESULTS: 2,913 patients contributed 11,491 person-years for the analysis of non-AIDS. 241 pre-specified non-AIDS events (including 84 deaths) and 89 AIDS events (including 10 deaths) occurred. The RR of developing pre-specified non-AIDS events for ID vs. non-ID was 1.96 (95% CI 1.37-2.81, p<0.001) in unadjusted analysis and 1.43 (0.94-2.17, pâ=â0.095) after controlling for current CD4 count. ID was not associated with the risk of AIDS events (aRR 0.76, 95% CI 0.41-1.38, pâ=â0.361). CONCLUSION: Compared to CD4 responders, patients with immuno-virological discordance may be at increased risk of developing non-AIDS events. Further studies are warranted to establish whether in patients with ID, strategies to directly modify CD4 count response may be needed besides the use of ART
LSST: from Science Drivers to Reference Design and Anticipated Data Products
(Abridged) We describe here the most ambitious survey currently planned in
the optical, the Large Synoptic Survey Telescope (LSST). A vast array of
science will be enabled by a single wide-deep-fast sky survey, and LSST will
have unique survey capability in the faint time domain. The LSST design is
driven by four main science themes: probing dark energy and dark matter, taking
an inventory of the Solar System, exploring the transient optical sky, and
mapping the Milky Way. LSST will be a wide-field ground-based system sited at
Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m
effective) primary mirror, a 9.6 deg field of view, and a 3.2 Gigapixel
camera. The standard observing sequence will consist of pairs of 15-second
exposures in a given field, with two such visits in each pointing in a given
night. With these repeats, the LSST system is capable of imaging about 10,000
square degrees of sky in a single filter in three nights. The typical 5
point-source depth in a single visit in will be (AB). The
project is in the construction phase and will begin regular survey operations
by 2022. The survey area will be contained within 30,000 deg with
, and will be imaged multiple times in six bands, ,
covering the wavelength range 320--1050 nm. About 90\% of the observing time
will be devoted to a deep-wide-fast survey mode which will uniformly observe a
18,000 deg region about 800 times (summed over all six bands) during the
anticipated 10 years of operations, and yield a coadded map to . The
remaining 10\% of the observing time will be allocated to projects such as a
Very Deep and Fast time domain survey. The goal is to make LSST data products,
including a relational database of about 32 trillion observations of 40 billion
objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures
available from https://www.lsst.org/overvie
The Molpro quantum chemistry package
Molpro is a general purpose quantum chemistry software package with a long development history. It was originally focused on accurate wavefunction calculations for small molecules but now has many additional distinctive capabilities that include, inter alia, local correlation approximations combined with explicit correlation, highly efficient implementations of single-reference correlation methods, robust and efficient multireference methods for large molecules, projection embedding, and anharmonic vibrational spectra. In addition to conventional input-file specification of calculations, Molpro calculations can now be specified and analyzed via a new graphical user interface and through a Python framework
The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe
The preponderance of matter over antimatter in the early Universe, the
dynamics of the supernova bursts that produced the heavy elements necessary for
life and whether protons eventually decay --- these mysteries at the forefront
of particle physics and astrophysics are key to understanding the early
evolution of our Universe, its current state and its eventual fate. The
Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed
plan for a world-class experiment dedicated to addressing these questions. LBNE
is conceived around three central components: (1) a new, high-intensity
neutrino source generated from a megawatt-class proton accelerator at Fermi
National Accelerator Laboratory, (2) a near neutrino detector just downstream
of the source, and (3) a massive liquid argon time-projection chamber deployed
as a far detector deep underground at the Sanford Underground Research
Facility. This facility, located at the site of the former Homestake Mine in
Lead, South Dakota, is approximately 1,300 km from the neutrino source at
Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino
charge-parity symmetry violation and mass ordering effects. This ambitious yet
cost-effective design incorporates scalability and flexibility and can
accommodate a variety of upgrades and contributions. With its exceptional
combination of experimental configuration, technical capabilities, and
potential for transformative discoveries, LBNE promises to be a vital facility
for the field of particle physics worldwide, providing physicists from around
the globe with opportunities to collaborate in a twenty to thirty year program
of exciting science. In this document we provide a comprehensive overview of
LBNE's scientific objectives, its place in the landscape of neutrino physics
worldwide, the technologies it will incorporate and the capabilities it will
possess.Comment: Major update of previous version. This is the reference document for
LBNE science program and current status. Chapters 1, 3, and 9 provide a
comprehensive overview of LBNE's scientific objectives, its place in the
landscape of neutrino physics worldwide, the technologies it will incorporate
and the capabilities it will possess. 288 pages, 116 figure
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
Herschel Gould Belt Survey Observations of Dense Cores in the Cepheus Flare Clouds
Abstract: We present Herschel SPIRE and PACS maps of the Cepheus Flare clouds L1157, L1172, L1228, L1241, and L1251, observed by the Herschel Gould Belt Survey of nearby star-forming molecular clouds. Through modified blackbody fits to the SPIRE and PACS data, we determine typical cloud column densities of (0.5â1.0) Ă 1021 cmâ2 and typical cloud temperatures of 14â15 K. Using the getsources identification algorithm, we extract 832 dense cores from the SPIRE and PACS data at 160â500 ÎŒm. From placement in a mass versus size diagram, we consider 303 to be candidate prestellar cores, and 178 of these to be ârobustâ prestellar cores. From an independent extraction of sources at 70 ÎŒm, we consider 25 of the 832 dense cores to be protostellar. The distribution of background column densities coincident with candidate prestellar cores peaks at (2â4) Ă 1021 cmâ2. About half of the candidate prestellar cores in Cepheus may have formed as a result of the widespread fragmentation expected to occur within filaments of âtranscriticalâ line mass. The lognormal robust prestellar core mass function (CMF) drawn from all five Cepheus clouds peaks at 0.56 Mâ and has a width of âŒ0.5 dex, similar to that of Aquilaâs CMF. Indeed, the width of Cepheusâs aggregate CMF is similar to the stellar system initial mass function (IMF). The similarity of CMF widths in different clouds and the system IMF suggests a common, possibly turbulent origin for seeding the fluctuations that evolve into prestellar cores and stars
The Concise Guide to PHARMACOLOGY 2023/24:Introduction and Other Protein Targets
The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16176. In addition to this overview, in which are identified 'Other protein targets' which fall outside of the subsequent categorisation, there are six areas of focus: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.</p
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