Light the towel : narrative and the negotiated unconscious

This investigation is a practice-based inquiry. It takes place in the context of writing and editing a novel manuscript: The earth does not get fat (Prendergast 2012). The unpublished novel manuscript is a fractured narrative, a tale told in multiple first-person voices. One of the problems the writer encountered, as the novel developed, was a problem from the perspective of logic and continuity: the stories did not fit together in a linear way. As a result, the writer felt estranged from the writing and, at the same time, strangely familiar with it. Despite having produced the narrative, the writer felt that it was ‘other’. This paper summarises the writer's methodology; it explains the writer's attachment to this fractured style of telling. This fractured style is assessed within the context of the mind's ability to produce its effects without full consciousness. The analysis of authorial intention therefore focuses upon the influence of altered states of consciousness upon narrative material. In particular, the writer uses Andreas Mavromatis’ (1987) work on hypnagogia: described as ‘the unique state of consciousness between wakefulness and sleep’ to describe the experience of the operation of the unconscious in authorial intention.

X-ray velocimetry within the ex vivo carotid artery

X-ray velocimetry offers a non-invasive method by which blood flow, blood velocity and wall shear stress can be measured in arteries prone to atherosclerosis. Analytical tools for measuring haemodynamics in artificial arteries have previously been developed and here the first quantification of haemodynamics using X-ray velocimetry in a living mammalian artery under physiologically relevant conditions is demonstrated. Whole blood seeded with a clinically used ultrasound contrast agent was pumped with a steady flow through live carotid arterial tissue from a rat, which was kept alive in a physiological salt solution. Pharmacological agents were then used to produce vascular relaxation. Velocity measurements were acquired with a spatial resolution of 14 µm × 14 µm and at a rate of 5000 acquisitions per second. Subtle velocity changes that occur are readily measurable, demonstrating the ability of X-ray velocimetry to sensitively and accurately measure haemodynamics ex vivo. Future applications and possible limitations of the technique are discussed, which allows for detailed living tissue investigations to be carried out for various disease models, including atherosclerosis and diabetic vasculopathy.

Functional imaging to understand biomechanics : a critical tool for the study of biology, pathology and the development of pharmacological solutions

We present four case studies of the literature discussing the effects of physical forces on biological function. While the field of biomechanics has existed for many decades, it may be considered by some a poor cousin to biochemistry and other traditional fields of medical research. In these case studies, including cardiovascular and respiratory systems, we demonstrate that, in fact, many systems historically believed to be controlled by biochemistry are dominated by biomechanics. We discuss both the previous paradigms that have advanced research in these fields and the changing paradigms that will define the progressions of these fields for decades to come. In the case of biomechanical effects of flowing blood on the endothelium, this has been well understood for decades. In the cases of platelet activation and liquid clearance from the lungs during birth, these discoveries are far more recent and perhaps not as universally accepted. While only a few specific examples are examined here, it is clear that not enough attention is paid to the possible mechanical links to biological function. The continued development of these research areas, with the inclusion of physical effects, will hopefully provide new insight into disease development, progression, diagnosis and effective therapies.

Phase II trial of continuous low-dose temozolomide for patients with recurrent malignant glioma

Background In this phase II trial, we investigated the efficacy of a metronomic temozolomide schedule in the treatment of recurrent malignant gliomas (MGs).

Methods Eligible patients received daily temozolomide (50 mg/m2) continuously until progression. The primary endpoint was progression-free survival rate at 6 months in the glioblastoma cohort (N = 37). In an exploratory analysis, 10 additional recurrent grade III MG patients were enrolled. Correlative studies included evaluation of 76 frequent mutations in glioblastoma (iPLEX assay, Sequenom) aiming at establishing the frequency of potentially “drugable” mutations in patients entering recurrent MG clinical trials.

Results Among glioblastoma patients, median age was 56 y; median Karnofsky Performance Score (KPS) was 80; 62% of patients had been treated for ≥2 recurrences, including 49% of patients having failed bevacizumab. Treatment was well tolerated; clinical benefit (complete response + partial response + stable disease) was seen in 10 (36%) patients. Progression-free survival rate at 6 months was 19% and median overall survival was 7 months. Patients with previous bevacizumab exposure survived significantly less than bevacizumab-naive patients (median overall survival: 4.3 mo vs 13 mo; hazard ratio = 3.2; P = .001), but those patients had lower KPS (P = .04) and higher number of recurrences (P < .0001). Mutations were found in 13 of the 38 MGs tested, including mutations of EGFR (N = 10), IDH1 (N = 5), and ERBB2 (N = 1).

Conclusions In spite of a heavily pretreated population, including nearly half of patients having failed bevacizumab, the primary endpoint was met, suggesting that this regimen deserves further investigation. Results in bevacizumab-naive patients seemed particularly favorable, while results in bevacizumab-failing patients highlight the need to develop further treatment strategies for advanced MG.

Religious/spiritual well-being, coping styles and personality dimensions in people with substance use disorders

Religiosity and spirituality have been found to be negatively associated with a range of addictions. It has been suggested that religious/spiritual well-being might play an important role in the development, course and the recovery from addictive disorders. A sample of addiction in-patients (n=389) was assessed using the Multidimensional Inventory for Religious/Spiritual Well-Being (MI-RSWB) and compared with a matched group of non-addicted community controls (n=389). RSWB was found to be substantially lower in people with substance use disorders compared to the normal sample. Discriminate functional analysis showed that Experiences of Sense and Meaning, General Religiosity and Forgiveness were the dimensions of RSWB which strongly distinguished the groups. Within the group of people with substance use disorders, RSWB was strongly positively associated with the personality dimensions of Conscientiousness, Agreeableness and Openness as well as Sense of Coherence and positive Coping styles. The study suggests that therapeutic intervention programs focusing on building a positive and meaningful personal framework, akin to that of a religious/spiritual orientation, may contribute to positive outcomes in addiction treatment.