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.

Clinical consequences of mast cell heterogeneity

The heterogeneous morphological, biochemical and functional characteristics of mast cells from different species and from different tissue sites in the same species have been described for over 30 years. Far from being mere histochemical or pharmacological curiosities these differences have far reaching implications for therapeutic practice. This review concentrates on two important areas affected by mast cell heterogeneity, those of adverse reactions to therapeutic agents and the efficacy of anti-allergy therapy.

Behavioural consequences of imagining intergroup contact with stigmatized outgroups

We investigated whether imagining contact with an outgroup member would change intergroup behaviour. Participants who had imagined a positive interaction with an outgroup member or an unspecified stranger were told that they were about to take part in a discussion task with an outgroup member. They were taken to a room and asked to set out two chairs ready for the discussion while the experimenter left, ostensibly to find the other participant. The distance between the two chairs was then measured. Undergraduate students who imagined talking to an obese individual (Experiment 1) or a Muslim individual (Experiment 2) placed the chairs significantly closer than those in the control condition. They also reported more positive feelings and beliefs regarding Muslims. These findings highlight an important practical application of imagined contact: preparing people for successful face-to-face contact.

The social consequences of broken urban structures: a case study of Belfast

This article explores how the design and layout of the urban environment can have significant social impacts on working class communities whose access to employment and other necessary services depends largely on public transport and safe walk-able streets. It does so by considering a case study of Belfast. Although Belfast has a distinctive recent history as the site of political violence and territorial division, it also has a spatial configuration that emerged out of a modernising roads and redevelopment programme in the 1960s and 1970s. However, an understanding of contemporary Belfast, particularly its urban structure and form, requires n analysis of how the social impacts of such ubiquitous regional and urban planning practices were not addressed. The article argues that a culture of ‘politically safe’ bureaucratic inaction developed during the ‘war years’ has been sustained in the ‘new democracy’. In turn, this has had significant consequences for the functioning of the city. Major areas of derelict land around the city core together with the impediments created by regional road infrastructure have combined to create a doughnut city that, on the one hand, facilitates a commuting middle class, while on the other, discriminates against the poorest inner city communities. The article goes on to examine how an activist urban design group, known as the Forum for Alternative Belfast, has responded to these challenges. It focuses particularly on action-research undertaken during its 2010 Summer School which aimed to address issues of disconnection in inner North Belfast that affect some of the most territorialised and deprived communities in the city.

Enabling Social Work Students to Deal with the Consequences of Political Conflict: Engaging with Victim/Survivor Service Users and a ‘Pedagogy of Discomfort’

This paper describes the evaluation of an educational project, delivered in a Bachelor in Social Work degree (BSW) program in Northern Ireland. The project aimed to equip social work students to be more culturally competent in this divided society, with a central focus on including victim/survivor service users in social work training. A number of pedagogical approaches are noted, with particular consideration of Boler's ‘pedagogy of discomfort’ as a model that includes the multidimensional nature of the learning process when topics carry a high emotional tariff. The evaluation of the students' experience indicated that: there was strong support among students for the project; the unique contribution of service users was affirmed; and the project appeared to increase students' awareness and capacity to practice in a divided society. The evaluation of the trainers' experience highlighted key processes in the delivery of collaborative training. The authors argue that the lessons learned are broadly applicable to other forms of service user and carer involvement in social work training and in other societies in which health and social care professionals have to deal with the legacies of political conflict.

Long-term consequences of pain in human neonates

The low tactile threshold in preterm infants when they are in the neonatal intensive care unit (NICU), while their physiological systems are unstable and immature, potentially renders them more vulnerable to the effects of repeated invasive procedures. There is a small but growing literature on pain and tactile responsivity following procedural pain in the NICU, or early surgery. Long-term effects of repeated pain in the neonatal period on neurodevelopment await further research. However, there are multiple sources of stress in the NICU, which contribute to inducing high overall 'allostatic load', therefore determining specific effects of neonatal pain in human infants is challenging.

Assessing the consequences of traumatic brain injury

Research concerned with assessing the rehabilitation outcome for the survivor of traumatic brain injury has suffered from both conceptual and procedural difficulties. The purpose of this paper is twofold: to assess the psychometric features in instruments used in assessing outcome; and to describe a test development framework based on the principles of construct validity. A construct validation approach is viewed as a means of avoiding common measurement difficulties, as well as integrating perspectives important to this population. Emphasis has been given to the cognitive/social dimensions of recovery, as it is this area which has the greatest impact for rehabilitation success.

Consequences of infant maltreatment on child wellbeing

Child maltreatment is a major public health and social welfare problem. Evidence consistently shows that infants under one are more at risk of fatal injury, physical abuse and neglect than any other age group, mainly because they are almost completely dependent on others for their overall wellbeing and development. This article discusses the impact of infant maltreatment on children's health and wellbeing. It highlights the sizeable body of literature on the relationship between types of infant maltreatment and a variety of negative developmental, health and mental health consequences

Effect of membrane stiffness and cytoskeletal element density on mechanical stimuli within cells: an analysis of the consequences of ageing in cells

A finite element model of a single cell was created and used to investigate the effects of ageing on biophysical stimuli generated within a cell. Major cellular components were incorporated in the model: the membrane, cytoplasm, nucleus, microtubules, actin filaments, intermediate filaments, nuclear lamina, and chromatin. The model used multiple sets of tensegrity structures. Viscoelastic properties were assigned to the continuum components. To corroborate the model, a simulation of Atomic Force Microscopy (AFM) indentation was performed and results showed a force/indentation simulation with the range of experimental results.

Ageing was simulated by both increasing membrane stiffness (thereby modelling membrane peroxidation with age) and decreasing density of cytoskeletal elements (thereby modelling reduced actin density with age). Comparing normal and aged cells under indentation predicts that aged cells have a lower membrane area subjected to high strain compared to young cells, but the difference, surprisingly, is very small and would not be measurable experimentally. Ageing is predicted to have more significant effect on strain deep in the nucleus. These results show that computation of biophysical stimuli within cells are achievable with single-cell computational models whose force/displacement behaviour is within experimentally observed ranges. the models suggest only small, though possibly physiologically-significant, differences in internal biophysical stimuli between normal and aged cells.

Consequences of unlocking the cardiac myosin molecule in human myocarditis and cardiomyopathies

Myocarditis, often initiated by viral infection, may progress to autoimmune inflammatory heart disease, dilated cardiomyopathy and heart failure. Although cardiac myosin is a dominant autoantigen in animal models of myocarditis and is released from the heart during viral myocarditis, the characterization, role and significance of anti-cardiac myosin autoantibodies is poorly defined. In our study, we define the human cardiac myosin epitopes in human myocarditis and cardiomyopathies and establish a mechanism to explain how anti-cardiac myosin autoantibodies may contribute to heart disease. We show that autoantibodies to cardiac myosin in sera from myocarditis and dilated cardiomyopathies in humans targeted primarily epitopes in the S2 hinge region of cardiac myosin. In addition, anti-cardiac myosin antibodies in sera or purified IgG from myocarditis and cardiomyopathy targeted the beta-adrenergic receptor and induced antibody-mediated cAMP-dependent protein kinase A (PKA) cell signaling activity in heart cells. Antibody-mediated PKA activity in sera was abrogated by absorption with anti-human IgG. Antibody-mediated cell signaling of PKA was blocked by antigen-specific inhibition by human cardiac myosin or the beta-adrenergic receptor but not the alpha adrenergic receptor or bovine serum albumin. Propranolol, a beta blocker and inhibitor of the beta-adrenergic receptor pathway also blocked the antibody-mediated signaling of the beta-adrenergic receptor and PKA. The data suggest that IgG antibody against human cardiac myosin reacts with the beta-adrenergic receptor and triggers PKA signaling in heart cells. In summary, we have identified a new class of crossreactive autoantibodies against human cardiac myosin and the beta-adrenergic receptor in the heart. In addition, we have defined disease specific peptide epitopes in the human cardiac myosin rod S2 region in human myocarditis and cardiomyopathy as well as a mechanistic role of autoantibody in the pathogenesis of disease.