Biological consequences of nanoscale energy deposition near irradiated heavy atom nanoparticles

Gold nanoparticles (GNPs) are being proposed as contrast agents to enhance X-ray imaging and radiotherapy, seeking to take advantage of the increased X-ray absorption of gold compared to soft tissue. However, there is a great discrepancy between physically predicted increases in X-ray energy deposition and experimentally observed increases in cell killing. In this work, we present the first calculations which take into account the structure of energy deposition in the nanoscale vicinity of GNPs and relate this to biological outcomes, and show for the first time good agreement with experimentally observed cell killing by the combination of X-rays and GNPs. These results are not only relevant to radiotherapy, but also have implications for applications of heavy atom nanoparticles in biological settings or where human exposure is possible because the localised energy deposition high-lighted by these results may cause complex DNA damage, leading to mutation and carcinogenesis.

Monitoring and repair of an impact damaged prestressed bridge

This paper details the monitoring and repair of an impact damaged prestressed concrete bridge. The repair was required following an impact from a low-loader carrying an excavator while passing underneath the bridge. The repair was carried out by preloading the bridge in the vicinity of the damage to relieve some prestressing. This preload was removed following the hardening and considerable strength gain of the repair material. The true behaviour of damaged prestressed concrete bridges during repair is difficult to estimate theoretically due to lack of benchmarking and inadequacy of assumed damage models. A network of strain gauges at locations of interest was thus installed during the entire period of repair. Effects of various activities were qualitatively and quantitatively observed. The interaction and rapid, model-free calibration of damaged and undamaged beams, including identification of damaged gauges were also probed. This full scale experiment is expected to be of interest and benefit to the practising engineer and the researcher alike.

The impact of biomarkers in multivariate algorithms for bladder cancer diagnosis in patients with hematuria

BACKGROUND: We appraised 23 biomarkers previously associated with urothelial cancer in a case-control study. Our aim was to determine whether single biomarkers and/or multivariate algorithms significantly improved on the predictive power of an algorithm based on demographics for prediction of urothelial cancer in patients presenting with hematuria. METHODS: Twenty-two biomarkers in urine and carcinoembryonic antigen (CEA) in serum were evaluated using enzyme-linked immunosorbent assays (ELISAs) and biochip array technology in 2 patient cohorts: 80 patients with urothelial cancer, and 77 controls with confounding pathologies. We used Forward Wald binary logistic regression analyses to create algorithms based on demographic variables designated prior predicted probability (PPP) and multivariate algorithms, which included PPP as a single variable. Areas under the curve (AUC) were determined after receiver-operator characteristic (ROC) analysis for single biomarkers and algorithms. RESULTS: After univariate analysis, 9 biomarkers were differentially expressed (t test; P

A phase I study of combined docetaxel and repeated high activity Re-186-HEDP in castration-resistant prostate cancer (CRPC) metastatic to bone (the TAXIUM trial)

Purpose Bone-seeking radiopharmaceuticals have palliative benefit in castration-resistant prostate cancer (CRPC) metastatic to bone. Recent studies have shown improvement of survival and quality of life when radiopharmaceuticals were given repeatedly or in combination with chemotherapy. We designed a phase I study combining docetaxel and Re-186-labelled hydroxyethylidene diphosphonate (HEDP) in men with CRPC and bone metastases to evaluate toxicity.

Service User and Carer Involvement in Role-Plays to Assess Readiness for Practice

Service user and carer involvement in social work education is now well established since its inception as a compulsory requirement in the social work curriculum in the United Kingdom in 2003. Since then, there have been many examples of how such involvement has been approached by education providers. Nevertheless, one of the key obstacles and challenges in this field continues to centre on the need to achieve non-tokenistic user involvement which cements the engagement of service users and carers at the heart of social work education. This paper describes one such initiative where service user and carer colleagues in a university in Northern Ireland have been actively involved in the assessment of first year social work students’ preparation for their first period of practice learning. The paper presents the background to this initiative explaining how the project unfolded; the detailed preparations that were involved and the evidence gathered from evaluations undertaken with the students, service users and carers, and academic colleagues who were all involved. We believe that the findings from this project can contribute to the advancement of existing knowledge in the field in exploring and recommending creative methodologies for user involvement in social work education.

Just how controversial is evidential holism?

This paper is an examination of evidential holism, a prominent position in epistemology and the philosophy of science which claims that experiments only ever confirm or refute entire theories. The position is historically associated with W.V. Quine, and it is at once both popular and notorious, as well as being largely under-described. But even though there’s no univocal statement of what holism is or what it does, philosophers have nevertheless made substantial assumptions about its content and its truth. Moreover they have drawn controversial and important conclusions from these assumptions. In this paper I distinguish three types of evidential holism and argue that the most oft-cited and controversial thesis is entirely unmotivated. The other two theses are much overlooked, but are well-motivated and free from controversial implications.

Evidential Holism and Indispensability Arguments

The indispensability argument is a method for showing that abstract mathematical objects exist (call this mathematical Platonism). Various versions of this argument have been proposed (§1). Lately, commentators seem to have agreed that a holistic indispensability argument (§2) will not work, and that an explanatory indispensability argument is the best candidate. In this paper I argue that the dominant reasons for rejecting the holistic indispensability argument are mistaken. This is largely due to an overestimation of the consequences that follow from evidential holism. Nevertheless, the holistic indispensability argument should be rejected, but for a different reason (§3)—in order that an indispensability argument relying on holism can work, it must invoke an unmotivated version of evidential holism. Such an argument will be unsound. Correcting the argument with a proper construal of evidential holism means that it can no longer deliver mathematical Platonism as a conclusion: such an argument for Platonism will be invalid. I then show how the reasons for rejecting the holistic indispensability argument importantly constrain what kind of account of explanation will be permissible in explanatory versions (§4).

Social Work Students Learn about Social Work Values from Service Users and Carers

Teaching on social work values is centrally important in social work education as a core aspect of underpinning knowledge in preparing students for practice. This paper describes an innovative project occurring within the first year of the degree in social work, where service users and carers have assisted students with their understanding of social work values. The positive contribution of service users and carers in facilitating students to make links between theory and practice is now well documented. Applying this user perspective to the educational domain of values, however, is relatively uncharted territory given the challenges that have traditionally accompanied the teaching of values. Importantly, this paper describes the ‘value talk’ which occurred when first-year students sought further meaning from service-user and carer groups in their community settings following classroom teaching on values. The paper not only discusses the detailed preparations involved in the project but also the learning which resulted, drawing on the evaluation findings from the students and participating groups. Whilst the findings show that the students' understanding of social work values has been most significantly influenced by the contributions from service users and carers, it is recognized that further research is needed to monitor the longer term impact on social work students' practice after they qualify.

Nanodosimetric effects of gold nanoparticles in megavoltage radiation therapy

Background and purpose: The addition of gold nanoparticles (GNPs) to tumours leads to an increase in dose due to their high density and energy absorption coefficient, making it a potential radiosensitiser. However, experiments have observed radiosensitisations significantly larger than the increase in dose alone, including at megavoltage energies where gold's relative energy absorption is lowest. This work investigates whether GNPs create dose inhomogeneities on a sub-cellular scale which combine with non-linear dose dependence of cell survival to be the source of radiosensitisation at megavoltage energies.

Cell survival responses after exposure to modulated radiation fields.

In the present study survival responses were determined in cells with differing radiosensitivity, specifically primary fibroblast (AG0-1522B), human breast cancer (MDA-MB-231), human prostate cancer (DU-145) and human glioma (T98G) cells, after exposure to modulated radiation fields delivered by shielding 50% of the tissue culture flask. A significant decrease (P < 0.05) in cell survival was observed in the shielded area, outside the primary treatment field (out-of-field), that was lower than predicted when compared to uniform exposures fitted to the linear-quadratic model. Cellular radiosensitivity was demonstrated to be an important factor in the level of response for both the in- and out-of-field regions. These responses were shown to be dependent on secretion-mediated intercellular communication, because inhibition of cellular secreted factors between the in- and out-of-field regions abrogated the response. Out-of-field cell survival was shown to increase after pretreatment of cells with agents known to inhibit factors involved in mediating radiation-induced bystander signaling (aminoguanidine, DMSO or cPTIO). These data illustrate a significant decrease in survival out-of-field, dependent upon intercellular communication, in several cell lines with varying radiosensitivity after exposure to a modulated radiation field. This study provides further evidence for the importance of intercellular signaling in modulated exposures, where dose gradients are present, and may inform the refinement of established radiobiological models to facilitate the optimization of advanced radiotherapy treatment plans.