2,663 research outputs found
Globular Cluster Distance Determinations
The present status of the distance scale to Galactic globular clusters is
reviewed. Six distance determination techniques which are deemed to be most
reliable are discussed in depth. These different techniques are used to
calibrate the absolute magnitude of the RR Lyrae stars. The various
calibrations fall into three groups. Main sequence fitting using Hipparcos
parallaxes, theoretical HB models and the RR Lyrae in the LMC all favor a
bright calibration, implying a `long' globular cluster distance scale. White
dwarf fitting and the astrometric distances yield a somewhat fainter RR Lyrae
calibration, while the statistical parallax solution yields faint RR Lyrae
stars implying a `short' distance scale to globular clusters. Various secondary
distance indicators discussed all favor the long distance scale. The `long' and
`short' distance scales differ by (0.31+/-0.16) mag. Averaging together all of
the different distance determinations yields Mv(RR) = (0.23+/-0.04)([Fe/H] +
1.6) + (0.56+/-0.12) mag.Comment: Invited review article to appear in: `Post-Hipparcos Cosmic Candles',
A. Heck & F. Caputo (Eds), Kluwer Academic Publ., Dordrecht, in pres
An eclipsing binary distance to the Large Magellanic Cloud accurate to 2 per cent
In the era of precision cosmology it is essential to determine the Hubble
Constant with an accuracy of 3% or better. Currently, its uncertainty is
dominated by the uncertainty in the distance to the Large Magellanic Cloud
(LMC) which as the second nearest galaxy serves as the best anchor point of the
cosmic distance scale. Observations of eclipsing binaries offer a unique
opportunity to precisely and accurately measure stellar parameters and
distances. The eclipsing binary method was previously applied to the LMC but
the accuracy of the distance results was hampered by the need to model the
bright, early-type systems used in these studies. Here, we present distance
determinations to eight long-period, late- type eclipsing systems in the LMC
composed of cool giant stars. For such systems we can accurately measure both
the linear and angular sizes of their components and avoid the most important
problems related to the hot early-type systems. Our LMC distance derived from
these systems is demonstrably accurate to 2.2 % (49.97 +/- 0.19 (statistical)
+/- 1.11 (systematic) kpc) providing a firm base for a 3 % determination of the
Hubble Constant, with prospects for improvement to 2 % in the future.Comment: 34 pages, 5 figures, 13 tables, published in the Nature, a part of
our data comes from new unpublished OGLE-IV photometric dat
Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer.
BackgroundT cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s.MethodsPatients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells). In trial C-9701 and C-9702, CART72 cells were administered in escalating doses up to 1010 total cells; in trial C-9701 CART72 cells were administered by intravenous infusion. In trial C-9702, CART72 cells were administered via direct hepatic artery infusion in patients with colorectal liver metastases. In both trials, a brief course of interferon-alpha (IFN-α) was given with each CART72 infusion to upregulate expression of TAG-72.ResultsFourteen patients were enrolled in C-9701 and nine in C-9702. CART72 manufacturing success rate was 100% with an average transduction efficiency of 38%. Ten patients were treated in CC-9701 and 6 in CC-9702. Symptoms consistent with low-grade, cytokine release syndrome were observed in both trials without clear evidence of on target/off tumor toxicity. Detectable, but mostly short-term (≤14 weeks), persistence of CART72 cells was observed in blood; one patient had CART72 cells detectable at 48 weeks. Trafficking to tumor tissues was confirmed in a tumor biopsy from one of three patients. A subset of patients had 111Indium-labeled CART72 cells injected, and trafficking could be detected to liver, but T cells appeared largely excluded from large metastatic deposits. Tumor biomarkers carcinoembryonic antigen (CEA) and TAG-72 were measured in serum; there was a precipitous decline of TAG-72, but not CEA, in some patients due to induction of an interfering antibody to the TAG-72 binding domain of humanized CC49, reflecting an anti-CAR immune response. No radiologic tumor responses were observed.ConclusionThese findings demonstrate the relative safety of CART72 cells. The limited persistence supports the incorporation of co-stimulatory domains in the CAR design and the use of fully human CAR constructs to mitigate immunogenicity
Do self-reported intentions predict clinicians behaviour: a systematic review.
Background: Implementation research is the scientific study of methods to promote the systematic uptake of
clinical research findings into routine clinical practice. Several interventions have been shown to be effective in
changing health care professionals' behaviour, but heterogeneity within interventions, targeted behaviours, and
study settings make generalisation difficult. Therefore, it is necessary to identify the 'active ingredients' in
professional behaviour change strategies. Theories of human behaviour that feature an individual's "intention" to
do something as the most immediate predictor of their behaviour have proved to be useful in non-clinical
populations. As clinical practice is a form of human behaviour such theories may offer a basis for developing a
scientific rationale for the choice of intervention to use in the implementation of new practice. The aim of this
review was to explore the relationship between intention and behaviour in clinicians and how this compares to
the intention-behaviour relationship in studies of non-clinicians.
Methods: We searched: PsycINFO, MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled
Trials, Science/Social science citation index, Current contents (social & behavioural med/clinical med), ISI
conference proceedings, and Index to Theses. The reference lists of all included papers were checked manually.
Studies were eligible for inclusion if they had: examined a clinical behaviour within a clinical context, included
measures of both intention and behaviour, measured behaviour after intention, and explored this relationship
quantitatively. All titles and abstracts retrieved by electronic searching were screened independently by two
reviewers, with disagreements resolved by discussion.
Discussion: Ten studies were found that examined the relationship between intention and clinical behaviours in
1623 health professionals. The proportion of variance in behaviour explained by intention was of a similar
magnitude to that found in the literature relating to non-health professionals. This was more consistently the case
for studies in which intention-behaviour correspondence was good and behaviour was self-reported. Though firm
conclusions are limited by a smaller literature, our findings are consistent with that of the non-health professional
literature. This review, viewed in the context of the larger populations of studies, provides encouragement for
the contention that there is a predictable relationship between the intentions of a health professional and their
subsequent behaviour. However, there remain significant methodological challenges
Multiple populations in globular clusters. Lessons learned from the Milky Way globular clusters
Recent progress in studies of globular clusters has shown that they are not
simple stellar populations, being rather made of multiple generations. Evidence
stems both from photometry and spectroscopy. A new paradigm is then arising for
the formation of massive star clusters, which includes several episodes of star
formation. While this provides an explanation for several features of globular
clusters, including the second parameter problem, it also opens new
perspectives about the relation between globular clusters and the halo of our
Galaxy, and by extension of all populations with a high specific frequency of
globular clusters, such as, e.g., giant elliptical galaxies. We review progress
in this area, focusing on the most recent studies. Several points remain to be
properly understood, in particular those concerning the nature of the polluters
producing the abundance pattern in the clusters and the typical timescale, the
range of cluster masses where this phenomenon is active, and the relation
between globular clusters and other satellites of our Galaxy.Comment: In press (The Astronomy and Astrophysics Review
The effectiveness of interventions to change six health behaviours: a review of reviews
Background: Several World Health Organisation reports over recent years have highlighted the high incidence of chronic diseases such as diabetes, coronary heart disease and cancer. Contributory factors include unhealthy diets, alcohol and tobacco use and sedentary lifestyles. This paper reports the findings of a review of reviews of behavioural change interventions to reduce unhealthy behaviours or promote healthy behaviours. We included six different health-related behaviours in the review: healthy eating, physical exercise, smoking, alcohol misuse, sexual risk taking (in young people) and illicit drug use. We excluded reviews which focussed on pharmacological treatments or those which required intensive treatments (e. g. for drug or alcohol dependency).
Methods: The Cochrane Library, Database of Abstracts of Reviews of Effectiveness (DARE) and several Ovid databases were searched for systematic reviews of interventions for the six behaviours (updated search 2008). Two reviewers applied the inclusion criteria, extracted data and assessed the quality of the reviews. The results were discussed in a narrative synthesis.
Results: We included 103 reviews published between 1995 and 2008. The focus of interventions varied, but those targeting specific individuals were generally designed to change an existing behaviour (e. g. cigarette smoking, alcohol misuse), whilst those aimed at the general population or groups such as school children were designed to promote positive behaviours (e. g. healthy eating). Almost 50% (n = 48) of the reviews focussed on smoking (either prevention or cessation). Interventions that were most effective across a range of health behaviours included physician advice or individual counselling, and workplace- and school-based activities. Mass media campaigns and legislative interventions also showed small to moderate effects in changing health behaviours. Generally, the evidence related to short-term effects rather than sustained/longer-term impact and there was a relative lack of evidence on how best to address inequalities.
Conclusions: Despite limitations of the review of reviews approach, it is encouraging that there are interventions that are effective in achieving behavioural change. Further emphasis in both primary studies and secondary analysis (e.g. systematic reviews) should be placed on assessing the differential effectiveness of interventions across different population subgroups to ensure that health inequalities are addressed.</p
Component analysis of nutritionally rich chloroplasts: recovery from conventional and unconventional green plant species
A study of the literature indicates that chloroplasts synthesise a range of molecules, many of which have nutritional value for humans, but as yet no one has established the nutritional credentials of chloroplasts recovered from plant cells. Chloroplast-rich-fractions (CRFs) were prepared from green plant species and the macro- and micronutrient composition compared with the whole leaf materials (WLMs). The results indicated that, on a dry weight basis, CRF material from a range of green biomass was enriched in lipids and proteins, and in a range of micronutrients compared with the WLM. Vitamins E, pro-vitamin A, and lutein were all greater in CRF preparations. Of the minerals, iron was most notably concentrated in CRF. Spinach CRFs possessed the highest α-tocopherol (62 mg 100 g-1 , dry weight (DW)), β-carotene (336 mg 100 g- 1 DW) and lutein (341 mg 100 g-1 DW) contents, whilst grass CRFs had the highest concentration of alpha-linolenic acid (ALA) (69.5 mg g-1). The higher concentrations of α-tocopherol, β-carotene, lutein, ALA and trace minerals (Fe and Mn) in CRFs suggest their potential use as concentrated ingredients in food formulations deficient in these nutrients
Systematically missing confounders in individual participant data meta-analysis of observational cohort studies.
One difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between an exposure and disease either are restricted to cohorts with full confounder information, or use all cohorts but do not fully adjust for confounding. We propose using a bivariate random-effects meta-analysis model to use information from all available cohorts while still adjusting for all the potential confounders. Our method uses both the fully adjusted and the partially adjusted estimated effects in the cohorts with full confounder information, together with an estimate of their within-cohort correlation. The method is applied to estimate the association between fibrinogen level and coronary heart disease incidence using data from 154,012 participants in 31 cohort
Agent based modelling helps in understanding the rules by which fibroblasts support keratinocyte colony formation
Background: Autologous keratincoytes are routinely expanded using irradiated mouse fibroblasts and bovine serum for clinical use. With growing concerns about the safety of these xenobiotic materials, it is desirable to culture keratinocytes in media without animal derived products. An improved understanding of epithelial/mesenchymal interactions could assist in this.
Methodology/Principal Findings: A keratincyte/fibroblast o-culture model was developed by extending an agent-based keratinocyte colony formation model to include the response of keratinocytes to both fibroblasts and serum. The model was validated by comparison of the in virtuo and in vitro multicellular behaviour of keratinocytes and fibroblasts in single and co-culture in Greens medium. To test the robustness of the model, several properties of the fibroblasts were changed to investigate their influence on the multicellular morphogenesis of keratinocyes and fibroblasts. The model was then used to generate hypotheses to explore the interactions of both proliferative and growth arrested fibroblasts with keratinocytes. The key predictions arising from the model which were confirmed by in vitro experiments were that 1) the ratio of fibroblasts to keratinocytes would critically influence keratinocyte colony expansion, 2) this ratio needed to be optimum at the beginning of the co-culture, 3) proliferative fibroblasts would be more effective than irradiated cells in expanding keratinocytes and 4) in the presence of an adequate number of fibroblasts, keratinocyte expansion would be independent of serum.
Conclusions: A closely associated computational and biological approach is a powerful tool for understanding complex biological systems such as the interactions between keratinocytes and fibroblasts. The key outcome of this study is the finding that the early addition of a critical ratio of proliferative fibroblasts can give rapid keratinocyte expansion without the use of irradiated mouse fibroblasts and bovine serum
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