876 research outputs found
Systems biological and mechanistic modelling of radiation-induced cancer
This paper summarises the five presentations at the First International Workshop on Systems Radiation Biology that were concerned with mechanistic models for carcinogenesis. The mathematical description of various hypotheses about the carcinogenic process, and its comparison with available data is an example of systems biology. It promises better understanding of effects at the whole body level based on properties of cells and signalling mechanisms between them. Of these five presentations, three dealt with multistage carcinogenesis within the framework of stochastic multistage clonal expansion models, another presented a deterministic multistage model incorporating chromosomal aberrations and neoplastic transformation, and the last presented a model of DNA double-strand break repair pathways for second breast cancers following radiation therapy
Dioxin Induces Genomic Instability in Mouse Embryonic Fibroblasts
Ionizing radiation and certain other exposures have been shown to induce genomic instability (GI), i.e., delayed genetic damage observed many cell generations later in the progeny of the exposed cells. The aim of this study was to investigate induction of GI by a nongenotoxic carcinogen, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Mouse embryonic fibroblasts (C3H10T1/2) were exposed to 1, 10 or 100 nM TCDD for 2 days. Micronuclei (MN) and expression of selected cancer-related genes were assayed both immediately and at a delayed point in time (8 days). For comparison, similar experiments were done with cadmium, a known genotoxic agent. TCDD treatment induced an elevated frequency of MN at 8 days, but not directly after the exposure. TCDD-induced alterations in gene expression were also mostly delayed, with more changes observed at 8 days than at 2 days. Exposure to cadmium produced an opposite pattern of responses, with pronounced effects immediately after exposure but no increase in MN and few gene expression changes at 8 days. Although all responses to TCDD alone were delayed, menadione-induced DNA damage (measured by the Comet assay), was found to be increased directly after a 2-day TCDD exposure, indicating that the stability of the genome was compromised already at this time point. The results suggested a flat dose-response relationship consistent with dose-response data reported for radiation-induced GI. These findings indicate that TCDD, although not directly genotoxic, induces GI, which is associated with impaired DNA damage response
Service use and costs for people with headache: a UK primary care study
This paper aims to estimate the service and social costs of headache presenting in primary care and to identify predictors of headache costs. Patients were recruited from GP practices in England and service use and lost employment recorded. Predictors of cost were identified using regression models. Service and social costs were available on 288 and 282 patients, respectively. Average service costs over 3 months were ÂŁ117 whilst total costs (including lost production) were ÂŁ582. Patients referred to neurologists had service costs that were ÂŁ82 higher than those not referred (90% CI ÂŁ36âÂŁ128). Costs including lost employment were higher by ÂŁ150, but this was not significant (90% CI -ÂŁ139âÂŁ439). The annual mean service and social costs, weighted to represent population rates of referral, were ÂŁ468 and ÂŁ2328, respectively. Higher costs were significantly related to pain. Age was linked to higher service costs and lower social costs. The figures extrapolated to the whole of the UK suggest ÂŁ956 million due to service use and ÂŁ4.8 billion including lost employment. These are likely to be underestimates because many people experiencing headaches do not consult their GP
Cellular Radiosensitivity: How much better do we understand it?
Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies.
Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation
Magnetization dynamics of weakly interacting sub-100 nm square artificial spin ices
Artificial Spin Ice (ASI), consisting of a two dimensional array of nanoscale magnetic elements, provides a fascinating opportunity to observe the physics of out-of-equilibrium systems. Initial studies concentrated on the static, frozen state, whilst more recent studies have accessed the out-of-equilibrium dynamic, fluctuating state. This opens up exciting possibilities such as the observation of systems exploring their energy landscape through monopole quasiparticle creation, potentially leading to ASI magnetricity, and to directly observe unconventional phase transitions. In this work we have measured and analysed the magnetic relaxation of thermally active ASI systems by means of SQUID magnetometry. We have investigated the effect of the interaction strength on the magnetization dynamics at different temperatures in the range where the nanomagnets are thermally active. We have observed that they follow an Arrhenius-type NĂ©el-Brown behaviour. An unexpected negative correlation of the average blocking temperature with the interaction strength is also observed, which is supported by Monte Carlo simulations. The magnetization relaxation measurements show faster relaxation for more strongly coupled nanoelements with similar dimensions. The analysis of the stretching exponents obtained from the measurements suggest 1-D chain-like magnetization dynamics. This indicates that the nature of the interactions between nanoelements lowers the dimensionality of the ASI from 2-D to 1-D. Finally, we present a way to quantify the effective interaction energy of a square ASI system, and compare it to the interaction energy computed with micromagnetic simulations
Standardisation of labial salivary gland histopathology in clinical trials in primary Sjögren's syndrome
Labial salivary gland (LSG) biopsy is used in the classification of primary Sjögren's syndrome (PSS) and in patient stratification in clinical trials. It may also function as a biomarker. The acquisition of tissue and histological interpretation is variable and needs to be standardised for use in clinical trials. A modified European League Against Rheumatism consensus guideline development strategy was used. The steering committee of the ad hoc working group identified key outstanding points of variability in LSG acquisition and analysis. A 2-day workshop was held to develop consensus where possible and identify points where further discussion/data was needed. These points were reviewed by a subgroup of experts on PSS histopathology and then circulated via an online survey to 50 stakeholder experts consisting of rheumatologists, histopathologists and oral medicine specialists, to assess level of agreement (0â10 scale) and comments. Criteria for agreement were a mean score â„6/10 and 75% of respondents scoring â„6/10. Thirty-nine (78%) experts responded and 16 points met criteria for agreement. These points are focused on tissue requirements, identification of the characteristic focal lymphocytic sialadenitis, calculation of the focus score, identification of germinal centres, assessment of the area of leucocyte infiltration, reporting standards and use of prestudy samples for clinical trials. We provide standardised consensus guidance for the use of labial salivary gland histopathology in the classification of PSS and in clinical trials and identify areas where further research is required to achieve evidence-based consensus
Search for rare quark-annihilation decays, B --> Ds(*) Phi
We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context
of the Standard Model, these decays are expected to be highly suppressed since
they proceed through annihilation of the b and u-bar quarks in the B- meson.
Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected
with the BABAR detector at SLAC. We find no evidence for these decays, and we
set Bayesian 90% confidence level upper limits on the branching fractions BF(B-
--> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results
are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid
Communications
Accreting Millisecond X-Ray Pulsars
Accreting Millisecond X-Ray Pulsars (AMXPs) are astrophysical laboratories
without parallel in the study of extreme physics. In this chapter we review the
past fifteen years of discoveries in the field. We summarize the observations
of the fifteen known AMXPs, with a particular emphasis on the multi-wavelength
observations that have been carried out since the discovery of the first AMXP
in 1998. We review accretion torque theory, the pulse formation process, and
how AMXP observations have changed our view on the interaction of plasma and
magnetic fields in strong gravity. We also explain how the AMXPs have deepened
our understanding of the thermonuclear burst process, in particular the
phenomenon of burst oscillations. We conclude with a discussion of the open
problems that remain to be addressed in the future.Comment: Review to appear in "Timing neutron stars: pulsations, oscillations
and explosions", T. Belloni, M. Mendez, C.M. Zhang Eds., ASSL, Springer;
[revision with literature updated, several typos removed, 1 new AMXP added
Cost-efficiency assessment of Advanced Life Support (ALS) courses based on the comparison of advanced simulators with conventional manikins
<p>Abstract</p> <p>Background</p> <p>Simulation is an essential tool in modern medical education. The object of this study was to assess, in cost-effective measures, the introduction of new generation simulators in an adult life support (ALS) education program.</p> <p>Methods</p> <p>Two hundred fifty primary care physicians and nurses were admitted to ten ALS courses (25 students per course). Students were distributed at random in two groups (125 each). Group A candidates were trained and tested with standard ALS manikins and Group B ones with new generation emergency and life support integrated simulator systems.</p> <p>Results</p> <p>In group A, 98 (78%) candidates passed the course, compared with 110 (88%) in group B (p < 0.01). The total cost of conventional courses was âŹ7689 per course and the cost of the advanced simulator courses was âŹ29034 per course (p < 0.001). Cost per passed student was âŹ392 in group A and âŹ1320 in group B (p < 0.001).</p> <p>Conclusion</p> <p>Although ALS advanced simulator systems may slightly increase the rate of students who pass the course, the cost-effectiveness of ALS courses with standard manikins is clearly superior.</p
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