Simulating photodynamic therapy for the treatment of glioblastoma using Monte Carlo radiative transport

Funding: LF acknowledges financial support from the UK Research and Innovation (UKRI) Engineering and Physical Sciences Research Council (EPSRC) Centre for Doctoral Training in Applied Photonics (Grant No. EP/S022821/1) and the Laser Research and Therapy Fund (Grant No. SC030850).Significance Glioblastoma (GBM) is a rare but deadly form of brain tumor with a low median survival rate of 14.6 months, due to its resistance to treatment. An independent simulation of the INtraoperative photoDYnamic therapy for GliOblastoma (INDYGO) trial, a clinical trial aiming to treat the GBM resection cavity with photo- dynamic therapy (PDT) via a laser coupled balloon device, is demonstrated. Aim To develop a framework providing increased understanding for the PDT treatment, its parameters, and their impact on the clinical outcome. Approach We use Monte Carlo radiative transport techniques within a computational brain model containing a GBM to simulate light path and PDT effects. Treatment parameters (laser power, photosensitizer concentration, and irradiation time) are considered, as well as PDT’s impact on brain tissue temperature.  Results The simulation suggests that 39% of post-resection GBM cells are killed at the end of treatment when using the standard INDYGO trial protocol (light fluence = 200 J∕cm2 at balloon wall) and assuming an initial photosensitizer concentration of 5 μM. Increases in treatment time and light power (light fluence = 400 J∕cm2 at balloon wall) result in further cell kill but increase brain cell temperature, which potentially affects treatment safety. Increasing the p hotosensitizer concentration produces the most significant increase in cell kill, with 61% of GBM cells killed when doubling concentration to 10 μM and keeping the treatment time and power the same. According to these simulations, the standard trial protocol is reasonably well optimized with improvements in cell kill difficult to achieve without potentially dangerous increases in temperature. To improve treatment outcome, focus should be placed on improving the photosensitizer.  Conclusions With further development and optimization, the simulation could have potential clinical benefit and be used to help plan and optimize intraoperative PDT treatment for GBM.Peer reviewe

"Engaging with birth stories in pregnancy: a hermeneutic phenomenological study of women's experiences across two generations"

BACKGROUND: The birth story has been widely understood as a crucial source of knowledge about childbirth. What has not been reported is the effect that birth stories may have on primigravid women's understandings of birth. Findings are presented from a qualitative study exploring how two generations of women came to understand birth in the milieu of other's stories. The prior assumption was that birth stories must surely have a positive or negative influence on listeners, steering them towards either medical or midwifery-led models of care. METHODS: A Heideggerian hermeneutic phenomenological approach was used. Twenty UK participants were purposively selected and interviewed. Findings from the initial sample of 10 women who were pregnant in 2012 indicated that virtual media was a primary source of birth stories. This led to recruitment of a second sample of 10 women who gave birth in the 1970s-1980s, to determine whether they were more able to translate information into knowledge via stories told through personal contact and not through virtual technologies RESULTS: Findings revealed the experience of 'being-in-the-world' of birth and of stories in that world. From a Heideggerian perspective, the birth story was constructed through 'idle talk' (the taken for granted assumptions of things, which come into being through language). Both oral stories and those told through technology were described as the 'modern birth story'. The first theme 'Stories are difficult like that', examines the birth story as problematic and considers how stories shape meaning. The second 'It's a generational thing', considers how women from two generations came to understand what their experience might be. The third 'Birth in the twilight of certainty,' examines women's experience of Being in a system of birth as constructed, portrayed and sustained in the stories being shared. CONCLUSIONS: The women pregnant in 2012 framed their expectations in the language of choice, whilst the women who birthed in the 1970s-1980s framed their experience in the language of safety. For both, however, the world of birth was the same; saturated with, and only legitimised by the birth of a healthy baby. Rather than creating meaningful understanding, the 'idle talk' of birth made both cohorts fearful of leaving the relative comfort of the 'system', and of claiming an alternative birth

Revolution from above in English schools: neoliberalism, the democratic commons and education

The ideas of the New Left and the recently emerged alter-globalisation movements are marginal within current policy debates concerning the English education system. Here I seek to demonstrate the interconnections between the New Left and the alter-globalisation movement and suggest that these ideas contain a powerful corrective to the increasingly authoritarian present. The next part of the article considers the development of neoliberalism both in a theoretical context and since the arrival of the new Conservative–Liberal government in the UK. Here I outline the rapid transformation of English schools under the academies programme and look at how it has been explicitly linked to ideas of ‘moral collapse’ evident in the popular discourse of ‘Broken Britain’. Especially significant in this respect has been the labelling of comprehensive schools as ‘failures’ and the explicit imposition of more authoritarian understandings of pedagogy. I seek to explore both the rapidity of this transformation in the context of the dissatisfaction with the idea of comprehensive schools shown by the political Right and the Third Way’s reworking of socialism. Finally I briefly consider more progressive alternatives for schools and education by returning to the idea of the democratic commons. In this respect, the cultural Left needs to explore more radical alternatives beyond the defence of comprehensive schooling which sounds both nostalgic and misplaced within our global times

Constitutivism

A brief explanation and overview of constitutivism

The development and validation of the Addiction-like Eating Behaviour Scale

Background: Overeating and obesity are frequently attributed to an addiction to food. However, there is currently a lack of evidence to support the idea that certain foods contain any specific addictive substance. An alternative approach is to focus on dimensions of observable behaviour, which may underpin a behavioural addiction to eating. To facilitate this, it is necessary to develop a tool to quantify addiction-like eating behaviour, which is not based on the clinical criteria for substance dependence. The current study provides initial validation of the Addiction-like Eating Behaviour Scale (AEBS). Methods: English speaking male and female participants (N=511) from a community sample completed the AEBS, alongside a range of other health- and eating-related questionnaires including the Yale Food Addiction Scale (YFAS) and Binge Eating Scale (BES). Participants also provided their height and weight to enable calculation of body mass index (BMI). Finally, to assess test–retest reliability, an additional 70 participants completed the AEBS twice, 2 weeks apart. Results: Principle components analysis revealed that a two-factor structure best accounted for the data. Factor 1 consisted of items that referred to appetitive drive, whereas factor two consisted of items that referred to dietary control practices. Both subscales demonstrated good internal reliability and test–retest reliability, and a confirmatory factor analysis confirmed the two-factor scale structure. AEBS scores correlated positively with body mass index (BMI) (P<0.001) and other self-report measures of overeating. Importantly, the AEBS significantly predicted variance in BMI above that accounted for by both the YFAS and BES (P=0.027). Conclusions: The AEBS provides a valid and reliable tool to quantify the behavioural features of a potential ‘eating addiction’. In doing so, the AEBS overcomes many limitations associated with applying substance-dependence criteria to eating

E.P. Thompson and cultural sociology: questions of poetics, capitalism and the commons

There is currently a need for cultural sociology to readdress the work of humanistic and cultural Marxism. While more recently much of this work has been dismissed the appearance of more radical social movements and the on-going crisis of neoliberalism suggests that it still has much to tell us. In this respect, this article seeks to readdress the writing of historian E.P.Thompson arguing that his work on the class based and other social movements, poetics, critique of positivism and economic reason, utopia and work on the idea of the commons all has much to offer more contemporary scholarship. While the article recognises that the cultural Marxism of figures like Thompson can-not simply be resurrected it does continue to offer a number of critical insights lacking from other traditions within cultural sociology. By readdressing the internal complexity of Thompson’s writing the argumentative strategy of this article suggests that cultural sociology needs to move beyond more simplistic understandings of cultural Marxism and more carefully explore what it has to offer

Non-pharmacological management of osteoporosis: a consensus of the Belgian Bone Club

This consensus article reviews the various aspects of the non-pharmacological management of osteoporosis, including the effects of nutriments, physical exercise, lifestyle, fall prevention, and hip protectors. Vertebroplasty is also briefly reviewed. Non-pharmacological management of osteoporosis is a broad concept. It must be viewed as an essential part of the prevention of fractures from childhood through adulthood and the old age. The topic also includes surgical procedures for the treatment of peripheral and vertebral fractures and the post-fracture rehabilitation. The present document is the result of a consensus, based on a systematic review and a critical appraisal of the literature. Diets deficient in calcium, proteins or vitamin D impair skeletal integrity. The effect of other nutriments is less clear, although an excessive consumption of sodium, caffeine, or fibres exerts negative effects on calcium balance. The deleterious effects of tobacco, excessive alcohol consumption and a low BMI are well accepted. Physical activity is of primary importance to reach optimal peak bone mass but, if numerous studies have shown the beneficial effects of various types of exercise on bone mass, fracture data as an endpoint are scanty. Fall prevention strategies are especially efficient in the community setting, but less evidence is available about their effectiveness in preventing fall-related injuries and fractures. The efficacy of hip protectors remains controversial. This is also true for vertebroplasty and kyphoplasty. Several randomized controlled studies had reported a short-term advantage of vertebroplasty over medical treatment for pain relief, but these findings have been questioned by recent sham-controlled randomized clinical studies

Philosophy of action

The philosophical study of human action begins with Plato and Aristotle. Their influence in late antiquity and the Middle Ages yielded sophisticated theories of action and motivation, notably in the works of Augustine and Aquinas.1 But the ideas that were dominant in 1945 have their roots in the early modern period, when advances in physics and mathematics reshaped philosophy

(Re) Locating community in relationships: questions for public policy

This is the author accepted manuscript. The final version is available from SAGE Publications via the DOI in this record.This paper argues that we should think of community as being about social relationships rather than a ‘thing’ that is ‘lost’, ‘found’ or ‘made’. The paper draws on the philosophy of Roberto Esposito and the sociology of David Studdert to highlight the overlaps in their approaches to community. Both argue that community is ontological, as unavoidably ‘with us’. The paper then draws upon two empirical examples to argue that this approach could enable a different kind of public policy in relation to community. Policy would focus on existing relationships as the starting point for any efforts to effect social change. The implications for contemporary debates about localism are explored at the end of the paper.I am very grateful to David Studdert and Valerie Walkerdine for inviting me to the workshop on community and localism held at Cardiff University in April 2014 that stimulated this special issue of Sociological Review. I am also very grateful to the Leverhulme Trust for the research funding and to Nick Coke, Tessy Britton and Laura Billings for their invaluable contributions to the arguments made. The comments from three referees, the editors and Patrick Devine-Wright were extremely helpful in improving the paper

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children