1,843 research outputs found
The Galactic Distribution of OH/IR Stars
Wetensch. publicatieFaculteit der Wiskunde en Natuurwetenschappe
Doubly charged silicon vacancy center, Si-N complexes, and photochromism in N and Si codoped diamond
Regulatory role of CD8(+ )T lymphocytes in bone marrow eosinophilopoiesis
BACKGROUND: There is a growing body of evidence to suggest that CD8(+ )T lymphocytes contribute to local allergen-induced eosinophilic inflammation. Since bone marrow (BM) responses are intricately involved in the induction of airway eosinophilia, we hypothesized that CD8(+ )T lymphocytes, as well as CD4(+ )T lymphocytes, may be involved in this process. METHODS: Several approaches were utilized. Firstly, mice overexpressing interleukin-5 (IL-5) in CD3(+ )T lymphocytes (NJ.1638; CD3(IL-5+ )mice) were bred with gene knockout mice lacking either CD4(+ )T lymphocytes (CD4(-/-)) or CD8(+ )T lymphocytes (CD8(-/-)) to produce CD3(IL-5+ )knockout mice deficient in CD4(+ )T lymphocytes (CD3(IL-5+)/CD4(-/-)) and CD8(+ )T lymphocytes (CD3(IL-5+)/CD8(-/-)), respectively. Secondly, CD3(+), CD4(+ )and CD8(+ )T lymphocytes from naïve CD3(IL-5+ )and C57BL/6 mice were adoptively transferred to immunodeficient SCID-bg mice to determine their effect on BM eosinophilia. Thirdly, CD3(IL-5+), CD3(IL-5+)/CD8(-/- )and CD3(IL-5+)/CD4(-/- )mice were sensitized and allergen challenged. Bone marrow and blood samples were collected in all experiments. RESULTS: The number of BM eosinophils was significantly reduced in CD3(IL-5+)/CD8(-/- )mice compared to CD3(IL-5+ )mice and CD3(IL-5+)/CD4(-/- )mice. Serum IL-5 was significantly higher in CD3(IL-5+)/CD4(-/- )mice compared to CD3(IL-5+ )mice but there was no difference in serum IL-5 between CD3(IL-5+)/CD4(-/- )and CD3(IL-5+)/CD8(-/- )mice. Adoptive transfer of CD8(+), but not CD4(+ )T lymphocytes from naïve CD3(IL-5+ )and C57BL/6 mice restored BM eosinophilia in immunodeficient SCID-bg mice. Additionally, allergen challenged CD3(IL-5+)/CD8(-/- )mice developed lower numbers of BM eosinophils compared to CD3(IL-5+ )mice and CD3(IL-5+)/CD4(-/- )mice. CONCLUSION: This study shows that CD8(+ )T lymphocytes are intricately involved in the regulation of BM eosinophilopoiesis, both in non-sensitized as well as sensitized and allergen challenged mice
The social value of a QALY : raising the bar or barring the raise?
Background: Since the inception of the National Institute for Health and Clinical Excellence (NICE) in England,
there have been questions about the empirical basis for the cost-per-QALY threshold used by NICE and whether
QALYs gained by different beneficiaries of health care should be weighted equally. The Social Value of a QALY
(SVQ) project, reported in this paper, was commissioned to address these two questions. The results of SVQ were
released during a time of considerable debate about the NICE threshold, and authors with differing perspectives
have drawn on the SVQ results to support their cases. As these discussions continue, and given the selective use of
results by those involved, it is important, therefore, not only to present a summary overview of SVQ, but also for
those who conducted the research to contribute to the debate as to its implications for NICE.
Discussion: The issue of the threshold was addressed in two ways: first, by combining, via a set of models, the
current UK Value of a Prevented Fatality (used in transport policy) with data on fatality age, life expectancy and
age-related quality of life; and, second, via a survey designed to test the feasibility of combining respondents’
answers to willingness to pay and health state utility questions to arrive at values of a QALY. Modelling resulted in
values of £10,000-£70,000 per QALY. Via survey research, most methods of aggregating the data resulted in values
of a QALY of £18,000-£40,000, although others resulted in implausibly high values. An additional survey, addressing
the issue of weighting QALYs, used two methods, one indicating that QALYs should not be weighted and the
other that greater weight could be given to QALYs gained by some groups.
Summary: Although we conducted only a feasibility study and a modelling exercise, neither present compelling
evidence for moving the NICE threshold up or down. Some preliminary evidence would indicate it could be
moved up for some types of QALY and down for others. While many members of the public appear to be open to
the possibility of using somewhat different QALY weights for different groups of beneficiaries, we do not yet have
any secure evidence base for introducing such a system
Endothelial Dysfunction in Resuscitated Cardiac Arrest (ENDO-RCA): safety and efficacy of low-dose prostacyclin administration and blood pressure target in addition to standard therapy, as compared to standard therapy alone, in post-cardiac arrest syndrome patients: study protocol for a randomized controlled trial
Association between sports type and overuse injuries of extremities in children and adolescents: a systematic review
Cooperation, Norms, and Revolutions: A Unified Game-Theoretical Approach
Cooperation is of utmost importance to society as a whole, but is often
challenged by individual self-interests. While game theory has studied this
problem extensively, there is little work on interactions within and across
groups with different preferences or beliefs. Yet, people from different social
or cultural backgrounds often meet and interact. This can yield conflict, since
behavior that is considered cooperative by one population might be perceived as
non-cooperative from the viewpoint of another.
To understand the dynamics and outcome of the competitive interactions within
and between groups, we study game-dynamical replicator equations for multiple
populations with incompatible interests and different power (be this due to
different population sizes, material resources, social capital, or other
factors). These equations allow us to address various important questions: For
example, can cooperation in the prisoner's dilemma be promoted, when two
interacting groups have different preferences? Under what conditions can costly
punishment, or other mechanisms, foster the evolution of norms? When does
cooperation fail, leading to antagonistic behavior, conflict, or even
revolutions? And what incentives are needed to reach peaceful agreements
between groups with conflicting interests?
Our detailed quantitative analysis reveals a large variety of interesting
results, which are relevant for society, law and economics, and have
implications for the evolution of language and culture as well
Long-term (trophic) purinergic signalling: purinoceptors control cell proliferation, differentiation and death
The purinergic signalling system, which uses purines and pyrimidines as chemical transmitters, and purinoceptors as effectors, is deeply rooted in evolution and development and is a pivotal factor in cell communication. The ATP and its derivatives function as a 'danger signal' in the most primitive forms of life. Purinoceptors are extraordinarily widely distributed in all cell types and tissues and they are involved in the regulation of an even more extraordinary number of biological processes. In addition to fast purinergic signalling in neurotransmission, neuromodulation and secretion, there is long-term (trophic) purinergic signalling involving cell proliferation, differentiation, motility and death in the development and regeneration of most systems of the body. In this article, we focus on the latter in the immune/defence system, in stratified epithelia in visceral organs and skin, embryological development, bone formation and resorption, as well as in cancer. Cell Death and Disease (2010) 1, e9; doi:10.1038/cddis.2009.11; published online 14 January 201
The Expression of BAFF, APRIL and TWEAK Is Altered in Eczema Skin but Not in the Circulation of Atopic and Seborrheic Eczema Patients
The TNF family cytokines BAFF (B-cell activating factor of the TNF family) and APRIL (a proliferation-inducing ligand) are crucial survival factors for B-cell development and activation. B-cell directed treatments have been shown to improve atopic eczema (AE), suggesting the involvement of these cytokines in the pathogenesis of AE. We therefore analyzed the expression of these TNF cytokines in AE, seborrheic eczema (SE) and healthy controls (HC). The serum/plasma concentration of BAFF, APRIL and a close TNF member TWEAK (TNF-like weak inducer of apoptosis) was measured by ELISA. The expression of these cytokines and their receptors in skin was analyzed by quantitative RT-PCR and immunofluorescence. Unlike other inflammatory diseases including autoimmune diseases and asthma, the circulating levels of BAFF, APRIL and TWEAK were not elevated in AE or SE patients compared with HCs and did not correlate with the disease severity or systemic IgE levels in AE patients. Interestingly, we found that the expression of these cytokines and their receptors was altered in positive atopy patch test reactions in AE patients (APT-AE) and in lesional skin of AE and SE patients. The expression of APRIL was decreased and the expression of BAFF was increased in eczema skin of AE and SE, which could contribute to a reduced negative regulatory input on B-cells. This was found to be more pronounced in APT-AE, the initiating acute stage of AE, which may result in dysregulation of over-activated B-cells. Furthermore, the expression levels of TWEAK and its receptor positively correlated to each other in SE lesions, but inversely correlated in AE lesions. These results shed light on potential pathogenic roles of these TNF factors in AE and SE, and pinpoint a potential of tailored treatments towards these factors in AE and SE
Increased activation of blood neutrophils after cigarette smoking in young individuals susceptible to COPD
Background: Cigarette smoking is the most important risk factor for Chronic Obstructive Pulmonary Disease (COPD). Only a subgroup of smokers develops COPD and it is unclear why these individuals are more susceptible to the detrimental effects of cigarette smoking. The risk to develop COPD is known to be higher in individuals with familial aggregation of COPD. This study aimed to investigate if acute systemic and local immune responses to cigarette smoke differentiate between individuals susceptible or non-susceptible to develop COPD, both at young (18-40 years) and old (40-75 years) age. Methods: All participants smoked three cigarettes in one hour. Changes in inflammatory markers in peripheral blood (at 0 and 3 hours) and in bronchial biopsies (at 0 and 24 hours) were investigated. Acute effects of smoking were analyzed within and between susceptible and non-susceptible individuals, and by multiple regression analysis. Results: Young susceptible individuals showed significantly higher increases in the expression of Fc gamma RII (CD32) in its active forms (A17 and A27) on neutrophils after smoking (p = 0.016 and 0.028 respectively), independently of age, smoking status and expression of the respective markers at baseline. Smoking had no significant effect on mediators in blood or inflammatory cell counts in bronchial biopsies. In the old group, acute effects of smoking were comparable between healthy controls and COPD patients. Conclusions: We show for the first time that COPD susceptibility at young age associates with an increased systemic innate immune response to cigarette smoking. This suggests a role of systemic inflammation in the early induction phase of COPD
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