372 research outputs found
Black Holes in Einstein-Aether Theory
We study black hole solutions in general relativity coupled to a unit
timelike vector field dubbed the "aether". To be causally isolated a black hole
interior must trap matter fields as well as all aether and metric modes. The
theory possesses spin-0, spin-1, and spin-2 modes whose speeds depend on four
coupling coefficients. We find that the full three-parameter family of local
spherically symmetric static solutions is always regular at a metric horizon,
but only a two-parameter subset is regular at a spin-0 horizon. Asymptotic
flatness imposes another condition, leaving a one-parameter family of regular
black holes. These solutions are compared to the Schwarzschild solution using
numerical integration for a special class of coupling coefficients. They are
very close to Schwarzschild outside the horizon for a wide range of couplings,
and have a spacelike singularity inside, but differ inside quantitatively. Some
quantities constructed from the metric and aether oscillate in the interior as
the singularity is approached. The aether is at rest at spatial infinity and
flows into the black hole, but differs significantly from the the 4-velocity of
freely-falling geodesics.Comment: 22 pages, 6 figures; v2: minor editing; v3: corrected overall sign in
twist formula and an error in the equation for the aether stress tensor.
Results unchanged since correct form was used in calculations; v4: corrected
minor typ
Widespread recombination, reassortment, and transmission of unbalanced compound viral genotypes in natural arenavirus infections.
Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential
Einstein-aether as a quantum effective field theory
The possibility that Lorentz symmetry is violated in gravitational processes
is relatively unconstrained by experiment, in stark contrast with the level of
accuracy to which Lorentz symmetry has been confirmed in the matter sector. One
model of Lorentz violation in the gravitational sector is Einstein-aether
theory, in which Lorentz symmetry is broken by giving a vacuum expectation
value to a dynamical vector field. In this paper we analyse the effective
theory for quantised gravitational and aether perturbations. We show that this
theory possesses a controlled effective expansion within dimensional
regularisation, that is, for any process there are a finite number of Feynman
diagrams which will contribute to a given order of accuracy. We find that there
is no log-running of the two-derivative phenomenological parameters, justifying
the use of experimental constraints for these parameters obtained over many
orders of magnitude in energy scale. Given the stringent experimental bounds on
two-derivative Lorentz-violating operators, we estimate the size of matter
Lorentz-violation which arises due to loop effects. This amounts to an
estimation of the natural size of coefficients for Lorentz-violating
dimension-six matter operators, which in turn can be used to obtain a new bound
on the two-derivative parameters of this theory.Comment: 21 page
The Tensor-Vector-Scalar theory and its cosmology
Over the last few decades, astronomers and cosmologists have accumulated vast
amounts of data clearly demonstrating that our current theories of fundamental
particles and of gravity are inadequate to explain the observed discrepancy
between the dynamics and the distribution of the visible matter in the
Universe. The Modified Newtonian Dynamics (MOND) proposal aims at solving the
problem by postulating that Newton's second law of motion is modified for
accelerations smaller than ~10^{-10}m/s^2. This simple amendment, has had
tremendous success in explaining galactic rotation curves. However, being
non-relativistic, it cannot make firm predictions for cosmology.
A relativistic theory called Tensor-Vector-Scalar (TeVeS) has been proposed
by Bekenstein building on earlier work of Sanders which has a MOND limit for
non-relativistic systems.
In this article I give a short introduction to TeVeS theory and focus on its
predictions for cosmology as well as some non-cosmological studies.Comment: 44 pages, topical review for Classical and Quantum Gravit
Lorentz violation, Gravity, Dissipation and Holography
We reconsider Lorentz Violation (LV) at the fundamental level. We show that
Lorentz Violation is intimately connected with gravity and that LV couplings in
QFT must always be fields in a gravitational sector. Diffeomorphism invariance
must be intact and the LV couplings transform as tensors under coordinate/frame
changes. Therefore searching for LV is one of the most sensitive ways of
looking for new physics, either new interactions or modifications of known
ones. Energy dissipation/Cerenkov radiation is shown to be a generic feature of
LV in QFT. A general computation is done in strongly coupled theories with
gravity duals. It is shown that in scale invariant regimes, the energy
dissipation rate depends non-triviallly on two characteristic exponents, the
Lifshitz exponent and the hyperscaling violation exponent.Comment: LateX, 51 pages, 9 figures. (v2) References and comments added.
Misprints correcte
Intravitreal antisense oligonucleotide sepofarsen in Leber congenital amaurosis type 10: a phase 1b/2 trial
CEP290-associated Leber congenital amaurosis type 10 (LCA10) is a retinal disease resulting in childhood blindness. Sepofarsen is an RNA antisense oligonucleotide targeting the c.2991+1655A>G variant in the CEP290 gene to treat LCA10. In this open-label, phase 1b/2 (NCT03140969), 12-month, multicenter, multiple-dose, dose-escalation trial, six adult patients and five pediatric patients received ≤4 doses of intravitreal sepofarsen into the worse-seeing eye. The primary objective was to evaluate sepofarsen safety and tolerability via the frequency and severity of ocular adverse events (AEs); secondary objectives were to evaluate pharmacokinetics and efficacy via changes in functional outcomes. Six patients received sepofarsen 160 µg/80 µg, and five patients received sepofarsen 320 µg/160 µg. Ten of 11 (90.9%) patients developed ocular AEs in the treated eye (5/6 with 160 µg/80 µg; 5/5 with 320 µg/160 µg) versus one of 11 (9.1%) in the untreated eye; most were mild in severity and dose dependent. Eight patients developed cataracts, of which six (75.0%) were categorized as serious (2/3 with 160 µg/80 µg; 4/5 with 320 µg/160 µg), as lens replacement was required. As the 160-µg/80-µg group showed a better benefit–risk profile, higher doses were discontinued or not initiated. Statistically significant improvements in visual acuity and retinal sensitivity were reported (post hoc analysis). The manageable safety profile and improvements reported in this trial support the continuation of sepofarsen development
Research, evidence and policymaking: the perspectives of policy actors on improving uptake of evidence in health policy development and implementation in Uganda
<p>Abstract</p> <p>Background</p> <p>Use of evidence in health policymaking plays an important role, especially in resource-constrained settings where informed decisions on resource allocation are paramount. Several knowledge translation (KT) models have been developed, but few have been applied to health policymaking in low income countries. If KT models are expected to explain evidence uptake and implementation, or lack of it, they must be contextualized and take into account the specificity of low income countries for example, the strong influence of donors. The main objective of this research is to elaborate a Middle Range Theory (MRT) of KT in Uganda that can also serve as a reference for other low- and middle income countries.</p> <p>Methods</p> <p>This two-step study employed qualitative approaches to examine the principal barriers and facilitating factors to KT. Step 1 involved a literature review and identification of common themes. The results informed the development of the initial MRT, which details the facilitating factors and barriers to KT at the different stages of research and policy development. In Step 2, these were further refined through key informant interviews with policymakers and researchers in Uganda. Deductive content and thematic analysis was carried out to assess the degree of convergence with the elements of the initial MRT and to identify other emerging issues.</p> <p>Results</p> <p>Review of the literature revealed that the most common emerging facilitating factors could be grouped under institutional strengthening for KT, research characteristics, dissemination, partnerships and political context. The analysis of interviews, however, showed that policymakers and researchers ranked institutional strengthening for KT, research characteristics and partnerships as the most important. New factors emphasized by respondents were the use of mainstreamed structures within MoH to coordinate and disseminate research, the separation of roles between researchers and policymakers, and the role of the community and civil society in KT.</p> <p>Conclusions</p> <p>This study refined an initial MRT on KT in policymaking in the health sector in Uganda that was based on a literature review. It provides a framework that can be used in empirical research of the process of KT on specific policy issues.</p
Effects of a demand-led evidence briefing service on the uptake and use of research evidence by commissioners of health services: protocol for a controlled before and after study
Background
Clinical Commissioning Groups (CCGs) are mandated to use research evidence effectively to ensure optimum use of resources by the National Health Service (NHS), both in accelerating innovation and in stopping the use of less effective practices and models of service delivery. We intend to evaluate whether access to a demand-led evidence service improves uptake and use of research evidence by NHS commissioners compared with less intensive and less targeted alternatives.
Methods/design
This is a controlled before and after study involving CCGs in the North of England. Participating CCGs will receive one of three interventions to support the use of research evidence in their decision-making: 1) consulting plus responsive push of tailored evidence; 2) consulting plus an unsolicited push of non-tailored evidence; or 3) standard service unsolicited push of non-tailored evidence. Our primary outcome will be changed at 12 months from baseline of a CCGs ability to acquire, assess, adapt and apply research evidence to support decision-making. Secondary outcomes will measure individual clinical leads and managers’ intentions to use research evidence in decision making. Documentary evidence of the use of the outputs of the service will be sought. A process evaluation will evaluate the nature and success of the interactions both within the sites and between commissioners and researchers delivering the service.
Discussion
The proposed research will generate new knowledge of direct relevance and value to the NHS. The findings will help to clarify which elements of the service are of value in promoting the use of research evidence. Those involved in NHS commissioning will be able to use the results to inform how best to build the infrastructure they need to acquire, assess, adapt and apply research evidence to support decision-making and to fulfil their statutory duties under the Health and Social Care Act
Modern tests of Lorentz invariance
Motivated by ideas about quantum gravity, a tremendous amount of effort over
the past decade has gone into testing Lorentz invariance in various regimes.
This review summarizes both the theoretical frameworks for tests of Lorentz
invariance and experimental advances that have made new high precision tests
possible. The current constraints on Lorentz violating effects from both
terrestrial experiments and astrophysical observations are presented.Comment: Modified and expanded discussions of various points. Numerous
references added. Version matches that accepted by Living Reviews in
Relativit
Knowledge translation research in population health: establishing a collaborative research agenda
<p>Abstract</p> <p>Background</p> <p>Despite the increasing mobilization of researchers and funding organizations around knowledge translation (KT) in Canada and elsewhere, many questions have been only partially answered, particularly in the field of population health. This article presents the results of a systematic process to draw out possible avenues of collaboration for researchers, practitioners and decision-makers who work in the area of KT. The main objective was to establish a research agenda on knowledge translation in population health.</p> <p>Methods</p> <p>Using the Concept Mapping approach, the research team wanted to identify priority themes for the development of research on KT in population health. Mapping is based on multivariate statistical analyses (multidimensional scaling and hierarchical cluster analysis) in which statements produced during a brainstorming session are grouped in weighted clusters. The final maps are a visual representation of the priority themes of research on KT. Especially designed for facilitating consensus in the understanding and organization of various concepts, the Concept Mapping method proved suitable for achieving this objective.</p> <p>Results</p> <p>The maps were produced by 19 participants from university settings, and from institutions within the health and social services network. Three main perspectives emerge from this operation: (1) The evaluation of the effectiveness of KT efforts is one of the main research priorities; (2) The importance of taking into consideration user contexts in any KT effort; (3) The challenges related to sharing power for decision-making and action-taking among various stakeholder groups. These perspectives open up avenues of collaboration for stakeholders who are involved in research on KT. Besides these three main perspectives, the concept maps reveal three other trends which should be emphasized.</p> <p>Conclusion</p> <p>The Concept Mapping process reported in this article aimed to provoke collective reflection on the research questions that should be studied, in order to foster coherence in research activities in the field of population health. Based on this, it is appropriate to continue to support the development of research projects in KT and the formation of research teams in this field. Research on KT must lead to concrete outcomes within communities that are interested in the question.</p
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