735 research outputs found
The clinical effectiveness and cost-effectiveness of computed tomography screening for lung cancer: systematic reviews.
Peer reviewedPublisher PD
A Signaling Protease Required for Melanization in Drosophila Affects Resistance and Tolerance of Infections
Organisms evolve two routes to surviving infectionsâthey can resist pathogen growth (resistance) and they can endure the pathogenesis of infection (tolerance). The sum of these two properties together defines the defensive capabilities of the host. Typically, studies of animal defenses focus on either understanding resistance or, to a lesser extent, tolerance mechanisms, thus providing little understanding of the relationship between these two mechanisms. We suggest there are nine possible pairwise permutations of these traits, assuming they can increase, decrease, or remain unchanged in an independent manner. Here we show that by making a single mutation in the gene encoding a protease, CG3066, active in the melanization cascade in Drosophila melanogaster, we observe the full spectrum of changes; these mutant flies show increases and decreases in their resistance and tolerance properties when challenged with a variety of pathogens. This result implicates melanization in fighting microbial infections and shows that an immune response can affect both resistance and tolerance to infections in microbe-dependent ways. The fly is often described as having an unsophisticated and stereotypical immune response where single mutations cause simple binary changes in immunity. We report a level of complexity in the fly's immune response that has strong ecological implications. We suggest that immune responses are highly tuned by evolution, since selection for defenses that alter resistance against one pathogen may change both resistance and tolerance to other pathogens
Drosophila eiger Mutants Are Sensitive to Extracellular Pathogens
We showed previously that eiger, the Drosophila tumor necrosis factor homolog, contributes to the pathology induced by infection with Salmonella typhimurium. We were curious whether eiger is always detrimental in the context of infection or if it plays a role in fighting some types of microbes. We challenged wild-type and eiger mutant flies with a collection of facultative intracellular and extracellular pathogens, including a fungus and Gram-positive and Gram-negative bacteria. The response of eiger mutants divided these microbes into two groups: eiger mutants are immunocompromised with respect to extracellular pathogens but show no change or reduced sensitivity to facultative intracellular pathogens. Hence, eiger helps fight infections but also can cause pathology. We propose that eiger activates the cellular immune response of the fly to aid clearance of extracellular pathogens. Intracellular pathogens, which can already defeat professional phagocytes, are unaffected by eiger
X-ray Emission and Corona of the Young Intermediate Mass Binary Ori E
Theta 1 Ori E is a young, moderate mass binary system, a rarely observed case
of spectral-type G-giants of about 3 Solar masses, which are still collapsing
towards the main sequence. We have obtained high resolution X-ray spectra with
Chandra and find that the system is very active and similar to coronal sources,
having emission typical of magnetically confined plasma: a broad temperature
distribution with a hot component and significant high energy continuum; narrow
emission lines from H- and He-like ions, as well as a range of Fe ions, and
relative luminosity, L_x/L_bol = 0.001. Density, while poorly constrained, is
consistent with the low density limits as determined from Mg XI and Ne IX
emission lines. Coronal elemental abundances are sub-Solar, with Ne being the
highest at about 0.4 times Solar. We find a possible trend in Trapezium hot
plasmas towards low relative abundances of Fe, O, and Ne, which is hard to
explain in terms of the dust depletion scenarios of low-mass young stars.
Variability was unusually low relative to other coronally active stars. The
emission is similar to post main-sequence G-stars. Coronal structures could be
compact or comparable to the dimensions of the stellar radii. We conclude that
the X-rays in theta 1 Ori E are generated by a convective dynamo.Comment: Accepted by ApJ (scheduled for Dec 2009, v707
The clinical effectiveness and cost-effectiveness of computed tomography screening for lung cancer : systematic reviews
Screening for lung cancer has been the subject of
debate for the past three decades. This has largely
stemmed from the results of chest X-ray screening
studies where improvements in survival were
obtained but without reductions in disease-specific,
or total, mortality. The debate raises two issues:
the design of studies to evaluate screening for
lung cancer, in particular the choice of
comparator; and the potential role of overdiagnosis of well-differentiated, slow-growing
tumours that would not have led to symptoms or
death in the lifetime of the affected patient.
Lung cancer is the leading cause of death from
cancer in the UK, killing approximately 34,000
people per year. By the time symptoms develop,
the tumour is often at an advanced stage and the
prognosis is bleak. Treatment at a less advanced
stage of disease with surgical resection has been
shown to substantially reduce mortality.
Screening would be attractive if it could detect
presymptomatic lung cancer at a stage when
surgical intervention is feasible
Peptide exchange on MHC-I by TAPBPR is driven by a negative allostery release cycle.
Chaperones TAPBPR and tapasin associate with class I major histocompatibility complexes (MHC-I) to promote optimization (editing) of peptide cargo. Here, we use solution NMR to investigate the mechanism of peptide exchange. We identify TAPBPR-induced conformational changes on conserved MHC-I molecular surfaces, consistent with our independently determined X-ray structure of the complex. Dynamics present in the empty MHC-I are stabilized by TAPBPR and become progressively dampened with increasing peptide occupancy. Incoming peptides are recognized according to the global stability of the final pMHC-I product and anneal in a native-like conformation to be edited by TAPBPR. Our results demonstrate an inverse relationship between MHC-I peptide occupancy and TAPBPR binding affinity, wherein the lifetime and structural features of transiently bound peptides control the regulation of a conformational switch located near the TAPBPR binding site, which triggers TAPBPR release. These results suggest a similar mechanism for the function of tapasin in the peptide-loading complex
The Role of Anorexia in Resistance and Tolerance to Infections in Drosophila
Infections initiate a signaling loop in which sick animals become anorexic, and the resulting change in diet alters the body's ability to fight infections in good and bad ways
Eff ect of antenatal multiple micronutrient supplementation on anthropometry and blood pressure in mid-childhood in Nepal: follow-up of a double-blind randomised controlled trial
Background In 2002â04, we did a randomised controlled trial in southern Nepal, and reported that children born to
mothers taking multiple micronutrient supplements during pregnancy had a mean birthweight 77 g greater than
children born to mothers taking iron and folic acid supplements. Children born to mothers in the study group were a
mean 204 g heavier at 2·5 years of age and their systolic blood pressure was a mean 2·5 mm Hg lower than children
born to mothers in the control group. We aimed to follow up the same children to mid-childhood (age 8·5 years) to
investigate whether these diff erences would be sustained.
Methods For this follow-up study, we identifi ed children from the original trial and measured anthropometry, body
composition with bioelectrical impedance (with population-specifi c isotope calibration), blood pressure, and renal
dimensions by ultrasound. We documented socioeconomic status, household food security, and air pollution. Main
outcomes of the follow-up at 8 years were Z scores for weight-for-age, height-for-age, and body-mass index (BMI)-forage
according to WHO Child Growth Standards for children aged 5â19 years, and blood pressure. This study is
registered with the International Standard Randomised Controlled Trial register, number ISRCTN88625934.
Findings Between Sept 21, 2011, and Dec 7, 2012, we assessed 841 children (422 in the control group and 419 in the
intervention group). Unadjusted diff erences (intervention minus control) in Z scores were 0·05 for weight-for-age
(95% CI â0·09 to 0·19), 0·02 in height-for-age (â0·10 to 0·15), and 0·04 in BMI-for-age (â0·09 to 0·18). We recorded
no diff erence in blood pressure. Adjusted diff erences were similar for all outcomes.
Interpretation We recorded no diff erences in phenotype between children born to mothers who received antenatal
multiple micronutrient or iron and folate supplements at age 8·5 years. Our fi ndings did not extend to physiological
diff erences or potential longer-term eff ects
Simplified Models for LHC New Physics Searches
This document proposes a collection of simplified models relevant to the
design of new-physics searches at the LHC and the characterization of their
results. Both ATLAS and CMS have already presented some results in terms of
simplified models, and we encourage them to continue and expand this effort,
which supplements both signature-based results and benchmark model
interpretations. A simplified model is defined by an effective Lagrangian
describing the interactions of a small number of new particles. Simplified
models can equally well be described by a small number of masses and
cross-sections. These parameters are directly related to collider physics
observables, making simplified models a particularly effective framework for
evaluating searches and a useful starting point for characterizing positive
signals of new physics. This document serves as an official summary of the
results from the "Topologies for Early LHC Searches" workshop, held at SLAC in
September of 2010, the purpose of which was to develop a set of representative
models that can be used to cover all relevant phase space in experimental
searches. Particular emphasis is placed on searches relevant for the first
~50-500 pb-1 of data and those motivated by supersymmetric models. This note
largely summarizes material posted at http://lhcnewphysics.org/, which includes
simplified model definitions, Monte Carlo material, and supporting contacts
within the theory community. We also comment on future developments that may be
useful as more data is gathered and analyzed by the experiments.Comment: 40 pages, 2 figures. This document is the official summary of results
from "Topologies for Early LHC Searches" workshop (SLAC, September 2010).
Supplementary material can be found at http://lhcnewphysics.or
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