In-vitro investigation of out-of-field cell survival following the delivery of conformal, intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) plans

The aim of this work is to determine the out-of-field survival of cells irradiated with either the primary field or scattered radiation in the presence and absence of intercellular communication following delivery of conformal, IMRT and VMAT treatment plans. Single beam, conformal, IMRT and VMAT plans were created to deliver 3 Gy to half the area of a T80 flask containing either DU-145 or AGO-1522 cells allowing intercellular communication between the in-and out-of-field cell populations. The same plans were delivered to a similar custom made phantom used to hold two T25 culture flasks, one flask in-field and one out-of-field to allow comparison of cell survival responses when intercellular communication is physically inhibited. Plans were created for the delivery of 8 Gy to the more radio-resistant DU-145 cells only in the presence and absence of intercellular communication. Cell survival was determined by clonogenic assay. In both cell lines, the out-of-field survival was not statistically different between delivery techniques for either cell line or dose. There was however, a statistically significant difference between survival out-of-field when intercellular communication was intact (single T80 culture flask) or inhibited (multiple T25 culture flasks) to in-field for all plans. No statistically significant difference was observed in-field with or without cellular communication to out-of-field for all plans. These data demonstrate out-of-field effects as important determinants of cell survival following exposure to modulated irradiation fields when cellular communication between differentially irradiated cell populations is present. This data is further evidence that refinement of existing radiobiological models to include indirect cell killing effects is required.

Social Class Variation in Risk: A Comparative Analysis of the Dynamics of Economic Vulnerability

A joint concern with multidimensionality and dynamics is a defining feature of the pervasive use of the terminology of social exclusion in the European Union. The notion of social exclusion focuses attention on economic vulnerability in the sense of exposure to risk and uncertainty. Sociological concern with these issues has been associated with the thesis that risk and uncertainty have become more pervasive and extend substantially beyond the working class. This paper combines features of recent approaches to statistical modelling of poverty dynamics and multidimensional deprivation in order to develop our understanding of the dynamics of economic vulnerability. An analysis involving nine countries and covering the first five waves of the European Community Household Panel shows that, across nations and time, it is possible to identify an economically vulnerable class. This class is characterized by heightened risk of falling below a critical resource level, exposure to material deprivation and experience of subjective economic stress. Cross-national differentials in persistence of vulnerability are wider than in the case of income poverty and less affected by measurement error. Economic vulnerability profiles vary across welfare regimes in a manner broadly consistent with our expectations. Variation in the impact of social class within and across countries provides no support for the argument that its role in structuring such risk has become much less important. Our findings suggest that it is possible to accept the importance of the emergence of new forms of social risk and acknowledge the significance of efforts to develop welfare states policies involving a shift of opportunities and decision making on to individuals without accepting the 'death of social class' thesis.

Does Job Search Monitoring Intensity Affect Unemployment? Evidence from Northern Ireland

Because unemployment benefit reforms typically package together a number of changes, few existing evaluations have been able to isolate the effects of changes in job search monitoring intensity on benefit recipient stocks or flows. Those few studies that do so draw mixed conclusions. This paper provides new estimates of monitoring impacts by exploiting plausibly exogenous periods where search monitoring has been temporarily withdrawn - with the regime otherwise unchanged - during a series of benefit office refurbishments in Northern Ireland. As we would expect from search theory, withdrawal of monitoring significantly increases the stock of unemployment benefit recipients via reduced outflows. © The London School of Economics and Political Science 2008.

Job search monitoring intensity, unemployment exit and job entry: Quasi-experimental evidence from the UK

Because unemployment benefit reforms tend to package together changes to job search requirements, monitoring and assistance, few existing studies have been able to empirically isolate the effects of job search monitoring intensity on the behaviour of unemployment benefit claimants. This paper exploits periods where monitoring has been temporarily withdrawn during a series of Benefit Office refurbishments - with the regime otherwise unchanged - to allow such identification. During these periods of zero monitoring the hazard rates for exits from claimant unemployment and for job entry both fall. © 2008 Elsevier B.V. All rights reserved.

Conformational Change of Mitochondrial Complex I Increases ROS Sensitivity During Ischemia

Aims: Myocardial ischemia/reperfusion (I/R) is associated with mitochondrial dysfunction and subsequent cardiomyocyte death. The generation of excessive quantities of reactive oxygen species (ROS) and resultant damage to mitochondrial enzymes is considered an important mechanism underlying reperfusion injury. Mitochondrial complex I can exist in two interconvertible states: active (A) and deactive or dormant (D). We have studied the active/deactive (A/D) equilibrium in several tissues under ischemic conditions in vivo and investigated the sensitivity of both forms of the heart enzyme to ROS.

Results: We found that in the heart, t½ of complex I deactivation during ischemia was 10?min, and that reperfusion resulted in the return of A/D equilibrium to its initial level. The rate of superoxide generation by complex I was higher in ischemic samples where content of the D-form was higher. Only the D-form was susceptible to inhibition by H2O2 or superoxide, whereas turnover-dependent activation of the enzyme resulted in formation of the A-form, which was much less sensitive to ROS. The mitochondrial-encoded subunit ND3, most likely responsible for the sensitivity of the D-form to ROS, was identified by redox difference gel electrophoresis.

Innovation: A combined in vivo and biochemical approach suggests that sensitivity of the mitochondrial system to ROS during myocardial I/R can be significantly affected by the conformational state of complex I, which may therefore represent a new therapeutic target in this setting.

Conclusion: The presented data suggest that transition of complex I into the D-form in the absence of oxygen may represent a key event in promoting cardiac injury during I/R.

‘Some Good Clean Fun’: Humour, Control and Subversion in an Advertising Agency

This article explores the relation between humour and control, drawing on participant observation in an organization in which humour was central to daily life. Keys is a leading advertising agency whose staff spent an unusually large amount of time sending humorous e-mails. Examining these e-mails in some depth, we unpack the role of humour in subverting various forms of control, including gender norms and managerial authority. We find the relation between humour, control and subversion to be ambiguous. Building upon current debates in organization studies, we develop the concept of humour based on our observations at Keys. Specifically, we argue that humour is always in excess of both control and subversion, a 'nicely impossible' object that cannot be captured. This article thus contributes to theoretical approaches on organizational humour, conceptualizing the concept of 'newness' through Judith Butler's re-reading of Derridean différance and the Lacanian Real. In addition, we contribute a novel empirical account of the study of e-mail list humour in a contemporary advertising firm. © 2012 Blackwell Publishing Ltd.

Insurgent Building: Spatial Practices of Resistance in the Bedouin-State Conflict in Southern Israel

In the con?ict between Bedouin representatives and government authorities in the southern Israeli Negev, the term ‘insurgent building’ refers to the construction of buildings erected in the full expectation that they will be demolished by the Israeli police shortly thereafter. This article analyses how insurgent building is employed as a spatial practice by emerging political actors to claim contested Bedouin landownership. Importantly, insurgent building relies on the ability of media and advocacy organizations to mobilize behind the issue. Most of the relevant scholarship takes the interpretative categories advanced by these actors at face value. Following anthropological debates regarding objecti?cation and categorization, I examine the context of a speci?c case of insurgent building. Emerging political actors who employ insurgent building often rely on prede?ned ethnic categories and clear-cut people–state polarities. This case demonstrates the need for a more differentiated understanding of multilayered local dynamics than the one offered by mainstream linear interpretations. At a more abstract level, political actors contribute to the reproduction of the very categories against which they mobilize.

Raiffeisenism abroad: why did German cooperative banking fail in Ireland but prosper in the Netherlands?

Why did imitations of Raiffeisen’s rural cooperative savings and loans associations work well in some European countries, but fail in others? This article considers the example of Raiffeisenism in Ireland and in the Netherlands. Raiffeisen banks arrived in both places at the same time, but had drastically different fates. In Ireland they were almost wiped out by the early 1920s, while in the Netherlands they proved to be a long-lasting institutional transplant. Raiffeisen banks were successful in the Netherlands because they operated in niche markets with few competitors, while rural financial markets in Ireland were unsegmented and populated by long- established incumbents, leaving little room for new players, whatever their institu- tional advantages. Dutch Raiffeisen banks were largely self-financing, closely integrated into the wider rural economy, and able to take advantage of economic and religious divisions in rural society. Their Irish counterparts were not.

Dose, dose-rate and field size effects on cell survival following exposure to non-uniform radiation fields

For the delivery of intensity-modulated radiation therapy (IMRT), highly modulated fields are used to achieve dose conformity across a target tumour volume. Recent in vitro evidence has demonstrated significant alterations in cell survival occurring out-of-field which cannot be accounted for on the basis of scattered dose. The radiobiological effect of area, dose and dose-rate on out-of-field cell survival responses following exposure to intensity-modulated radiation fields is presented in this study. Cell survival was determined by clonogenic assay in human prostate cancer (DU-145) and primary fibroblast (AG0-1522) cells following exposure to different modulated field configurations delivered using a X-Rad 225 kVp x-ray source. Uniform survival responses were compared to in- and out-of-field responses in which 25-99% of the cell population was shielded. Dose delivered to the out-of-field region was varied from 1.6-37.2% of that delivered to the in-field region using different levels of brass shielding. Dose rate effects were determined for 0.2-4 Gy min⁻¹ for uniform and modulated exposures with no effect seen in- or out-of-field. Survival responses showed little dependence on dose rate and area in- and out-of-field with a trend towards increased survival with decreased in-field area. Out-of-field survival responses were shown to scale in proportion to dose delivered to the in-field region and also local dose delivered out-of-field. Mathematical modelling of these findings has shown survival response to be highly dependent on dose delivered in- and out-of-field but not on area or dose rate. These data provide further insight into the radiobiological parameters impacting on cell survival following exposure to modulated irradiation fields highlighting the need for refinement of existing radiobiological models to incorporate non-targeted effects and modulated dose distributions.

The Relationship between Components of the Behavioural Phenotype in Prader-Willi Syndrome

Background

Repetitive questions and temper outbursts form part of the behavioural phenotype of Prader-Willi syndrome (PWS). We investigated the phenomenology of temper outbursts in PWS and their relationship with other PWS behavioural characteristics.

Method

Four individuals with PWS were observed (5-10 h), during a number of experimental and natural environment challenges, some of which were expected to trigger temper outbursts. Individual behaviours including crying, ignoring, arguing, questioning, stereotypy, frowning and posture changes were recorded and subjected to lag sequential analysis.

Results

All participants were significantly more likely to show repetitive questioning before more challenging behaviours such as crying, arguing or ignoring requests. Precursor behaviours such as frowning and stereotypical behaviour were identified in three participants.

Conclusions

Temper outbursts in PWS may be associated with other PWS behavioural phenotypic characteristics such as repetitive questions and 'stubbornness'. A progression of behaviours may lead up to the most challenging temper outburst behaviours. This may have important implications for effective coping strategies.

The relationship between the recognition of facial expressions and self-reported anger in people with intellectual disabilities

Background This study aims to examine the relationship between how individuals with intellectual disabilities report their own levels of anger, and the ability of those individuals to recognize emotions. It was hypothesized that increased expression of anger would be linked to lower ability to recognize facial emotional expressions and increased tendency to interpret facial expressions in a hostile or negative manner. It was also hypothesized increased levels of anger may lead to the altered perception of a particular emotion.

Method A cross-sectional survey design was used. Thirty participants completed a test of facial emotion recognition (FER), and a self-report anger inventory (Benson & Ivins 1992) as part of a structured interview.

Results Individuals with higher self-reported anger did not show significantly reduced performance in FER, or interpret facial expressions in a more hostile manner compared with individuals with less self-reported anger. However, they were less accurate in recognizing neutral facial emotions.

Conclusions It is tentatively suggested that individuals with high levels of anger may be likely to perceive emotional content in a neutral facial expression because of their high levels of emotional arousal.

The impact of foreign postings on accompanying military spouses: an ethnographic study

As part of an ethnographic study, the impact of foreign postings on spouses who accompany military personnel was explored. Individual interviews and focus groups with 34 British military spouses based in one location in southern Europe were conducted. Key findings suggested that reaction to a foreign posting was a reflection of personal attitudes, prior experiences, support, ability to adjust to change and strength of relationship with the serving spouse and community. For many the experience was positive due to the increased opportunity for family time, for others this helped to compensate for the difficulties experienced. Some military spouses experienced significant distress on the posting, particularly if the family was not well-supported. The potential implications of military spouses not adapting to foreign postings have significant implications for healthcare practice. Provision of more appropriate support resources before and during the posting would facilitate the transition for the military spouse and their family.