438 research outputs found
Manipulating the 5 dimensions of the EuroQol instrument: the effects on self-reporting actual health and valuing hypothetical health states
Background. The EQ-5D instrument has 5 dimensions. This article reports on the effects of manipulating a) the order in which the 5 dimensions are presented (appearing first v. last), b) splitting of the composite dimensions (“pain or discomfort” and “anxiety or depression”), and c) removing or “bolting off” 1 of the 5 EQ-5D dimensions at a time. The effects were examined in 2 contexts: 1) self-reporting health and 2) health state valuations. Methods. Three different types of discrete choice experiments (DCE) including a duration attribute were designed. An online survey with 12 subtypes, each with 10 DCE tasks, was designed and completed by 2494 members of the UK general public. Results. Of the 3 manipulations in the self-reporting context, only b) splitting anxiety or depression had a significant effect. In the health state valuation context, b) splitting level 5 pain or discomfort (relative to pain) and splitting level 5 anxiety or depression (relative to anxiety) had significant effects as did c) bolting off dimensions. Conclusions. We find that the values given to certain health dimensions are sensitive to the way in which it is described and the other health dimensions presented. Of particular interest is the effect of splitting composite dimensions: a given EQ-5D(-5L) profile may mean different things depending on whether the profile is used to self-report one’s health or to value hypothetical states, so that the health state values of EQ-5D(-5L) in population tariffs may not correspond to the states that patients self-report themselves in
Increasing condom use in heterosexual men: development of a theory-based interactive digital intervention
Increasing condom use to prevent sexually transmitted infections is a key public health goal. Interventions are more likely to be effective if they are theory- and evidence-based. The Behaviour Change Wheel (BCW) provides a framework for intervention development. To provide an example of how the BCW was used to develop an intervention to increase condom use in heterosexual men (the MenSS website), the steps of the BCW intervention development process were followed, incorporating evidence from the research literature and views of experts and the target population. Capability (e.g. knowledge) and motivation (e.g. beliefs about pleasure) were identified as important targets of the intervention. We devised ways to address each intervention target, including selecting interactive features and behaviour change techniques. The BCW provides a useful framework for integrating sources of evidence to inform intervention content and deciding which influences on behaviour to target
Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey
Although jawless vertebrates are apparently capable of adaptive immune responses, they have not been found to possess the recombinatorial antigen receptors shared by all jawed vertebrates. Our search for the phylogenetic roots of adaptive immunity in the lamprey has instead identified a new type of variable lymphocyte receptors (VLRs) composed of highly diverse leucine-rich repeats (LRR) sandwiched between amino- and carboxy-terminal LRRs. An invariant stalk region tethers the VLRs to the cell surface by means of a glycosyl-phosphatidyl-inositol anchor. To generate rearranged VLR genes of the diversity necessary for an anticipatory immune system, the single lamprey VLR locus contains a large bank of diverse LRR cassettes, available for insertion into an incomplete germline VLR gene. Individual lymphocytes express a uniquely rearranged VLR gene in monoallelic fashion. Different evolutionary strategies were thus used to generate highly diverse lymphocyte receptors through rearrangement of LRR modules in agnathans ( jawless fish) and of immunoglobulin gene segments in gnathostomes ( jawed vertebrates).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62870/1/nature02740.pd
The Epstein-Barr Virus G-Protein-Coupled Receptor Contributes to Immune Evasion by Targeting MHC Class I Molecules for Degradation
Epstein-Barr virus (EBV) is a human herpesvirus that persists as a largely subclinical infection in the vast majority of adults worldwide. Recent evidence indicates that an important component of the persistence strategy involves active interference with the MHC class I antigen processing pathway during the lytic replication cycle. We have now identified a novel role for the lytic cycle gene, BILF1, which encodes a glycoprotein with the properties of a constitutive signaling G-protein-coupled receptor (GPCR). BILF1 reduced the levels of MHC class I at the cell surface and inhibited CD8+ T cell recognition of
endogenous target antigens. The underlying mechanism involves physical association of BILF1 with MHC class I molecules, an increased turnover from the cell surface, and enhanced degradation via lysosomal proteases. The BILF1 protein of the closely related CeHV15 c1-herpesvirus of the Rhesus Old World primate (80% amino acid sequence identity) downregulated surface MHC class I similarly to EBV BILF1. Amongst the human herpesviruses, the GPCR encoded by the ORF74 of the KSHV c2-herpesvirus is most closely related to EBV BILF1 (15% amino acid sequence identity) but did not affect levels of surface MHC class I. An engineered mutant of BILF1 that was unable to activate G protein signaling pathways retained the ability to downregulate MHC class I, indicating that the immune-modulating and GPCR-signaling properties are two distinct functions of BILF1. These findings extend our understanding of the normal biology of an important human pathogen. The discovery of a third EBV lytic cycle gene that cooperates to interfere with MHC class I antigen processing underscores the importance of the need for EBV to be able to evade CD8+ T cell responses during the lytic replication cycle, at a time when such a large number of potential viral targets are expressed
An affordable, quality-assured community-based system for high-resolution entomological surveillance of vector mosquitoes that reflects human malaria infection risk patterns.
ABSTRACT: BACKGROUND: More sensitive and scalable entomological surveillance tools are required to monitor low levels of transmission that are increasingly common across the tropics, particularly where vector control has been successful. A large-scale larviciding programme in urban Dar es Salaam, Tanzania is supported by a community-based (CB) system for trapping adult mosquito densities to monitor programme performance. Methodology An intensive and extensive CB system for routine, longitudinal, programmatic surveillance of malaria vectors and other mosquitoes using the Ifakara Tent Trap (ITT-C) was developed in Urban Dar es Salaam, Tanzania, and validated by comparison with quality assurance (QA) surveys using either ITT-C or human landing catches (HLC), as well as a cross-sectional survey of malaria parasite prevalence in the same housing compounds. RESULTS: Community-based ITT-C had much lower sensitivity per person-night of sampling than HLC (Relative Rate (RR) [95% Confidence Interval (CI)] = 0.079 [0.051, 0.121], P < 0.001 for Anopheles gambiae s.l. and 0.153 [0.137, 0.171], P < 0.001 for Culicines) but only moderately differed from QA surveys with the same trap (0.536 [0.406,0.617], P = 0.001 and 0.747 [0.677,0.824], P < 0.001, for An. gambiae or Culex respectively). Despite the poor sensitivity of the ITT per night of sampling, when CB-ITT was compared with QA-HLC, it proved at least comparably sensitive in absolute terms (171 versus 169 primary vectors caught) and cost-effective (153US per An. gambiae caught) because it allowed more spatially extensive and temporally intensive sampling (4284 versus 335 trap nights distributed over 615 versus 240 locations with a mean number of samples per year of 143 versus 141). Despite the very low vectors densities (Annual estimate of about 170 An gambiae s.l bites per person per year), CB-ITT was the only entomological predictor of parasite infection risk (Odds Ratio [95% CI] = 4.43[3.027,7. 454] per An. gambiae or Anopheles funestus caught per night, P =0.0373). Discussion and conclusion CB trapping approaches could be improved with more sensitive traps, but already offer a practical, safe and affordable system for routine programmatic mosquito surveillance and clusters could be distributed across entire countries by adapting the sample submission and quality assurance procedures accordingly
The Pioneer Anomaly
Radio-metric Doppler tracking data received from the Pioneer 10 and 11
spacecraft from heliocentric distances of 20-70 AU has consistently indicated
the presence of a small, anomalous, blue-shifted frequency drift uniformly
changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was
interpreted as a constant sunward deceleration of each particular spacecraft at
the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of
the Newton's gravitational inverse-square law has become known as the Pioneer
anomaly; the nature of this anomaly remains unexplained. In this review, we
summarize the current knowledge of the physical properties of the anomaly and
the conditions that led to its detection and characterization. We review
various mechanisms proposed to explain the anomaly and discuss the current
state of efforts to determine its nature. A comprehensive new investigation of
the anomalous behavior of the two Pioneers has begun recently. The new efforts
rely on the much-extended set of radio-metric Doppler data for both spacecraft
in conjunction with the newly available complete record of their telemetry
files and a large archive of original project documentation. As the new study
is yet to report its findings, this review provides the necessary background
for the new results to appear in the near future. In particular, we provide a
significant amount of information on the design, operations and behavior of the
two Pioneers during their entire missions, including descriptions of various
data formats and techniques used for their navigation and radio-science data
analysis. As most of this information was recovered relatively recently, it was
not used in the previous studies of the Pioneer anomaly, but it is critical for
the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living
Reviews in Relativit
An energetic stellar outburst accompanied by circumstellar light echoes
Some classes of stars, including supernovae and novae, undergo explosive
outbursts that eject stellar material into space. In 2002, the previously
unknown variable star V838 Monocerotis brightened suddenly by a factor of about
10^4. Unlike a supernova or nova, V838 Mon did not explosively eject its outer
layers; rather, it simply expanded to become a cool supergiant with a
moderate-velocity stellar wind. Superluminal light echoes were discovered as
light from the outburst propagated into surrounding, pre-existing circumstellar
dust. Here we report high-resolution imaging and polarimetry of the light
echoes, which allow us to set direct geometric distance limits to the object.
At a distance of >6 kpc, V838 Mon at its maximum brightness was temporarily the
brightest star in the Milky Way. The presence of the circumstellar dust implies
that previous eruptions have occurred, and spectra show it to be a binary
system. When combined with the high luminosity and unusual outburst behavior,
these characteristics indicate that V838 Mon represents a hitherto unknown type
of stellar outburst, for which we have no completely satisfactory physical
explanation.Comment: To appear in Nature, March 27, 2003. 9 pages, 6 figure
Planetary population synthesis
In stellar astrophysics, the technique of population synthesis has been
successfully used for several decades. For planets, it is in contrast still a
young method which only became important in recent years because of the rapid
increase of the number of known extrasolar planets, and the associated growth
of statistical observational constraints. With planetary population synthesis,
the theory of planet formation and evolution can be put to the test against
these constraints. In this review of planetary population synthesis, we first
briefly list key observational constraints. Then, the work flow in the method
and its two main components are presented, namely global end-to-end models that
predict planetary system properties directly from protoplanetary disk
properties and probability distributions for these initial conditions. An
overview of various population synthesis models in the literature is given. The
sub-models for the physical processes considered in global models are
described: the evolution of the protoplanetary disk, the planets' accretion of
solids and gas, orbital migration, and N-body interactions among concurrently
growing protoplanets. Next, typical population synthesis results are
illustrated in the form of new syntheses obtained with the latest generation of
the Bern model. Planetary formation tracks, the distribution of planets in the
mass-distance and radius-distance plane, the planetary mass function, and the
distributions of planetary radii, semimajor axes, and luminosities are shown,
linked to underlying physical processes, and compared with their observational
counterparts. We finish by highlighting the most important predictions made by
population synthesis models and discuss the lessons learned from these
predictions - both those later observationally confirmed and those rejected.Comment: 47 pages, 12 figures. Invited review accepted for publication in the
'Handbook of Exoplanets', planet formation section, section editor: Ralph
Pudritz, Springer reference works, Juan Antonio Belmonte and Hans Deeg, Ed
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