2,091 research outputs found
Reputation Agent: Prompting Fair Reviews in Gig Markets
Our study presents a new tool, Reputation Agent, to promote fairer reviews
from requesters (employers or customers) on gig markets. Unfair reviews,
created when requesters consider factors outside of a worker's control, are
known to plague gig workers and can result in lost job opportunities and even
termination from the marketplace. Our tool leverages machine learning to
implement an intelligent interface that: (1) uses deep learning to
automatically detect when an individual has included unfair factors into her
review (factors outside the worker's control per the policies of the market);
and (2) prompts the individual to reconsider her review if she has incorporated
unfair factors. To study the effectiveness of Reputation Agent, we conducted a
controlled experiment over different gig markets. Our experiment illustrates
that across markets, Reputation Agent, in contrast with traditional approaches,
motivates requesters to review gig workers' performance more fairly. We discuss
how tools that bring more transparency to employers about the policies of a gig
market can help build empathy thus resulting in reasoned discussions around
potential injustices towards workers generated by these interfaces. Our vision
is that with tools that promote truth and transparency we can bring fairer
treatment to gig workers.Comment: 12 pages, 5 figures, The Web Conference 2020, ACM WWW 202
Tissue-specific calibration of extracellular matrix material properties by transforming growth factor-beta and Runx2 in bone is required for hearing
Publisher version: http://www.nature.com/embor/journal/v11/n10/full/embor2010135.htmlDA - 20100917 IS - 1469-3178 (Electronic) IS - 1469-221X (Linking) LA - ENG PT - JOURNAL ARTICLEDA - 20100917 IS - 1469-3178 (Electronic) IS - 1469-221X (Linking) LA - ENG PT - JOURNAL ARTICLEDA - 20100917 IS - 1469-3178 (Electronic) IS - 1469-221X (Linking) LA - ENG PT - JOURNAL ARTICLEPhysical cues, such as extracellular matrix stiffness, direct cell differentiation and support tissue-specific function. Perturbation of these cues underlies diverse pathologies, including osteoarthritis, cardiovascular disease and cancer. However, the molecular mechanisms that establish tissue-specific material properties and link them to healthy tissue function are unknown. We show that Runx2, a key lineage-specific transcription factor, regulates the material properties of bone matrix through the same transforming growth factor-beta (TGFbeta)-responsive pathway that controls osteoblast differentiation. Deregulated TGFbeta or Runx2 function compromises the distinctly hard cochlear bone matrix and causes hearing loss, as seen in human cleidocranial dysplasia. In Runx2(+/-) mice, inhibition of TGFbeta signalling rescues both the material properties of the defective matrix, and hearing. This study elucidates the unknown cause of hearing loss in cleidocranial dysplasia, and demonstrates that a molecular pathway controlling cell differentiation also defines material properties of extracellular matrix. Furthermore, our results suggest that the careful regulation of these properties is essential for healthy tissue functio
Complete analysis of the B-cell response to a protein antigen, from in vivo germinal centre formation to 3-D modelling of affinity maturation
Somatic hypermutation of immunoglobulin variable region genes occurs within germinal centres (GCs) and is the process responsible for affinity maturation of antibodies during an immune response. Previous studies have focused almost exclusively on the immune response to haptens, which may be unrepresentative of epitopes on protein antigens. In this study, we have exploited a model system that uses transgenic B and CD4<sup>+</sup> T cells specific for hen egg lysozyme (HEL) and a chicken ovalbumin peptide, respectively, to investigate a tightly synchronized immune response to protein antigens of widely differing affinities, thus allowing us to track many facets of the development of an antibody response at the antigen-specific B cell level in an integrated system <i>in</i> <i>vivo</i>. Somatic hypermutation of immunoglobulin variable genes was analysed in clones of transgenic B cells proliferating in individual GCs in response to HEL or the cross-reactive low-affinity antigen, duck egg lysozyme (DEL). Molecular modelling of the antibody–antigen interface demonstrates that recurring mutations in the antigen-binding site, selected in GCs, enhance interactions of the antibody with DEL. The effects of these mutations on affinity maturation are demonstrated by a shift of transgenic serum antibodies towards higher affinity for DEL in DEL-cOVA immunized mice. The results show that B cells with high affinity antigen receptors can revise their specificity by somatic hypermutation and antigen selection in response to a low-affinity, cross-reactive antigen. These observations shed further light on the nature of the immune response to pathogens and autoimmunity and demonstrate the utility of this novel model for studies of the mechanisms of somatic hypermutation
Optimality of mutation and selection in germinal centers
The population dynamics theory of B cells in a typical germinal center could
play an important role in revealing how affinity maturation is achieved.
However, the existing models encountered some conflicts with experiments. To
resolve these conflicts, we present a coarse-grained model to calculate the B
cell population development in affinity maturation, which allows a
comprehensive analysis of its parameter space to look for optimal values of
mutation rate, selection strength, and initial antibody-antigen binding level
that maximize the affinity improvement. With these optimized parameters, the
model is compatible with the experimental observations such as the ~100-fold
affinity improvements, the number of mutations, the hypermutation rate, and the
"all or none" phenomenon. Moreover, we study the reasons behind the optimal
parameters. The optimal mutation rate, in agreement with the hypermutation rate
in vivo, results from a tradeoff between accumulating enough beneficial
mutations and avoiding too many deleterious or lethal mutations. The optimal
selection strength evolves as a balance between the need for affinity
improvement and the requirement to pass the population bottleneck. These
findings point to the conclusion that germinal centers have been optimized by
evolution to generate strong affinity antibodies effectively and rapidly. In
addition, we study the enhancement of affinity improvement due to B cell
migration between germinal centers. These results could enhance our
understandings to the functions of germinal centers.Comment: 5 figures in main text, and 4 figures in Supplementary Informatio
The a-theorem and conformal symmetry breaking in holographic RG flows
We study holographic models describing an RG flow between two fixed points
driven by a relevant scalar operator. We show how to introduce a spurion field
to restore Weyl invariance and compute the anomalous contribution to the
generating functional in even dimensional theories. We find that the
coefficient of the anomalous term is proportional to the difference of the
conformal anomalies of the UV and IR fixed points, as expected from anomaly
matching arguments in field theory. For any even dimensions the coefficient is
positive as implied by the holographic a-theorem. For flows corresponding to
spontaneous breaking of conformal invariance, we also compute the two-point
functions of the energy-momentum tensor and the scalar operator and identify
the dilaton mode. Surprisingly we find that in the simplest models with just
one scalar field there is no dilaton pole in the two-point function of the
scalar operator but a stronger singularity. We discuss the possible
implications.Comment: 50 pages. v2: minor changes, added references, extended discussion.
v3: we have clarified some of the calculations and assumptions, results
unchanged. v4: published version in JHE
Multi-centre parallel arm randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based cognitive behavioural approach to managing fatigue in people with multiple sclerosis
Abstract (provisional)
Background
Fatigue is one of the most commonly reported and debilitating symptoms of multiple sclerosis (MS); approximately two-thirds of people with MS consider it to be one of their three most troubling symptoms. It may limit or prevent participation in everyday activities, work, leisure, and social pursuits, reduce psychological well-being and is one of the key precipitants of early retirement. Energy effectiveness approaches have been shown to be effective in reducing MS-fatigue, increasing self-efficacy and improving quality of life. Cognitive behavioural approaches have been found to be effective for managing fatigue in other conditions, such as chronic fatigue syndrome, and more recently, in MS. The aim of this pragmatic trial is to evaluate the clinical and cost-effectiveness of a recently developed group-based fatigue management intervention (that blends cognitive behavioural and energy effectiveness approaches) compared with current local practice.
Methods
This is a multi-centre parallel arm block-randomised controlled trial (RCT) of a six session group-based fatigue management intervention, delivered by health professionals, compared with current local practice. 180 consenting adults with a confirmed diagnosis of MS and significant fatigue levels, recruited via secondary/primary care or newsletters/websites, will be randomised to receive the fatigue management intervention or current local practice. An economic evaluation will be undertaken alongside the trial. Primary outcomes are fatigue severity, self-efficacy and disease-specific quality of life. Secondary outcomes include fatigue impact, general quality of life, mood, activity patterns, and cost-effectiveness. Outcomes in those receiving the fatigue management intervention will be measured 1 week prior to, and 1, 4, and 12 months after the intervention (and at equivalent times in those receiving current local practice). A qualitative component will examine what aspects of the fatigue management intervention participants found helpful/unhelpful and barriers to change.
Discussion
This trial is the fourth stage of a research programme that has followed the Medical Research Council guidance for developing and evaluating complex interventions. What makes the intervention unique is that it blends cognitive behavioural and energy effectiveness approaches. A potential strength of the intervention is that it could be integrated into existing service delivery models as it has been designed to be delivered by staff already working with people with MS. Service users will be involved throughout this research. Trial registration: Current Controlled Trials ISRCTN7651747
Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin
One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution
The utilisation of health research in policy-making: Concepts, examples and methods of assessment
The importance of health research utilisation in policy-making, and of understanding the
mechanisms involved, is increasingly recognised. Recent reports calling for more resources to
improve health in developing countries, and global pressures for accountability, draw greater
attention to research-informed policy-making. Key utilisation issues have been described for at
least twenty years, but the growing focus on health research systems creates additional dimensions.
The utilisation of health research in policy-making should contribute to policies that may eventually
lead to desired outcomes, including health gains. In this article, exploration of these issues is
combined with a review of various forms of policy-making. When this is linked to analysis of
different types of health research, it assists in building a comprehensive account of the diverse
meanings of research utilisation.
Previous studies report methods and conceptual frameworks that have been applied, if with varying
degrees of success, to record utilisation in policy-making. These studies reveal various examples of
research impact within a general picture of underutilisation.
Factors potentially enhancing utilisation can be identified by exploration of: priority setting;
activities of the health research system at the interface between research and policy-making; and
the role of the recipients, or 'receptors', of health research. An interfaces and receptors model
provides a framework for analysis.
Recommendations about possible methods for assessing health research utilisation follow
identification of the purposes of such assessments. Our conclusion is that research utilisation can
be better understood, and enhanced, by developing assessment methods informed by conceptual
analysis and review of previous studies
Risk Of Incidence Of Hock Burn And Pododermatitis In Broilers Reared Under Commercial Conditions
The most common lesions observed in commercial broiler farms are hock burns and pododermatitis, defined as necrotic lesions on the plantar surface of the footpads and in the hock of growing broilers, causing pain and compromising broiler welfare. The present study aimed at identifying the risks of hock burns and pododermatitis in broilers reared under commercial conditions on new or reused litter. Twenty-four 40-d-old broilers reared in two houses in a commercial broiler farm. The plantar surface of the footpads and the hocks of broiler were recorded using infrared thermal images. The incidence of hock burns in broilers reared on new litter was 0.72 times lower than those on reused litter. Broilers reared on new litter presented lower risk (0.75, RR<1) of presenting pododermatitis when compared to those reared on reused litter. When simulating the risk using a larger sample, the simulated risk of broilers presenting footpad and hock lesions when reared on new litter was 38% higher those reared on reused litter.19335736
A Measurement of Rb using a Double Tagging Method
The fraction of Z to bbbar events in hadronic Z decays has been measured by
the OPAL experiment using the data collected at LEP between 1992 and 1995. The
Z to bbbar decays were tagged using displaced secondary vertices, and high
momentum electrons and muons. Systematic uncertainties were reduced by
measuring the b-tagging efficiency using a double tagging technique. Efficiency
correlations between opposite hemispheres of an event are small, and are well
understood through comparisons between real and simulated data samples. A value
of Rb = 0.2178 +- 0.0011 +- 0.0013 was obtained, where the first error is
statistical and the second systematic. The uncertainty on Rc, the fraction of Z
to ccbar events in hadronic Z decays, is not included in the errors. The
dependence on Rc is Delta(Rb)/Rb = -0.056*Delta(Rc)/Rc where Delta(Rc) is the
deviation of Rc from the value 0.172 predicted by the Standard Model. The
result for Rb agrees with the value of 0.2155 +- 0.0003 predicted by the
Standard Model.Comment: 42 pages, LaTeX, 14 eps figures included, submitted to European
Physical Journal
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