• Ingen resultater fundet

were evaluated independently in a blinded fashion.

Results: Evidence of MRI-detected residual mesorectum was identified in 54 of 136 patients (39.7%). There was agreement with the pathology findings in 88 of 136 patients (64.7%). Residual mesorectum was more frequent in patients treated with PME (63%) than after total mesorectal excision (TME) (33%) or abdominoperineal resection (13%) (P<0.001). Localisation of residual mesorectum was peri-anastomotic in all cases following PME, while being distal to the anastomosis in 21% after TME. Pathology and MRI concurred that the distal resection margin after PME was less than 3 cm in more than one third.

Conclusion: Inadvertent residual mesorectum was commonly found on postoperative MRI, especially following PME.

O04.03 Tim van Hartevelt

TEMPORAL ASPECTS OF THE SENSE OF SMELL: A STUDY USING MAGNETOENCEPHALOGRAPHY

T.J. van Hartevelt1,6, T. Kjærgaard2, E.-M. Jegindø1, A.B.A. Stevner1,6, H.R.

Mohseni3, M.W. Woolrich3, C. Margot5, A. Møller1, T.Z. Aziz4, T. Ovesen2, M.L.

Kringelbach1,6

1Center of Functionally Integrative Neuroscience (CFIN), Aarhus University,

2Department of Otorhinolaryngology, Head and Neck Surgery, Aarhus University Hospital, 3Oxford Centre for Human Brain Activity (OHBA), University of Oxford, UK, 4Nuffield Department of Surgery, John Radcliffe Hospital, Oxford, UK, 5Firmenich SA, Geneva, Switzerland, 6Department of Psychiatry, University of Oxford, UK

The sense of smell is of great importance for food selection and repro-duction, especially in animals. Furthermore, the loss of sense of smell has been shown to be a common symptom in neurological or psychiatric disorders, such as Parkinson's disease. Although the sense of smell has been under-investigated in humans compared to other sensory modalities, neuroimaging studies in recent years have started to elucidate some of the mechanisms involved in human olfaction, including the differential spatial distribution of activity to positive and negative odours. Yet, neuroimaging studies have not yet started to investigate the temporal aspects of olfaction in humans.

In the current study, we used magnetoencephalography (MEG) to measure the spatial and temporal aspects of brain activity whilst odours were delivered to the participant’s nose. Six different odours (two pleasant, two unpleasant and two food related odours) were delivered using a purpose-built, computer-controlled, continuous air flow olfactometer, embedded in a continuous airflow of 6 litres per minute.

Negative odours are more likely to signal potentially dangerous substances such as spoiled food. We hypothesized that negative odours are processed not only in different areas of the brain, but are also processed faster than other types of odours including those perceived to be pleasant and food related.

The preliminary results show localised activity within the first 1000 milliseconds in the alpha band in the lateral orbitofrontal cortex and the

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anterior cingulate cortex for negative odours, while positive odours gave rise to activity in the mid-anterior orbitofrontal cortex and the insular cortex.

O04.04 Thomas Lyhne Ravkilde

PREDICTING TREATMENT DELIVERY SUCCESS OF ADVANCED RADIOTHERAPY TREATMENTS OF CANCER

T. Ravkilde1,2, P.J. Keall3, C. Grau1, 2, M. Høyer1,2, P.R. Poulsen1,2

1Department of Oncology, Aarhus University Hospital, Aarhus, Denmark,

2Department of Clinical Medicine, Aarhus University, Denmark, 3Sydney Medical School, University of Sydney, Sydney, Australia

In current radiotherapy treatments of moving tumors, the underlying assumptions of regular motion are not necessarily met. Moreover, the past has presented examples of treatment errors leading to severe

complications and lethal outcome, making it clear that dosimetric errors during treatment must be monitored. The aim of this study was to develop a method for reconstruction of the time-resolved delivery of dose during volumetric modulated arc therapy (VMAT) of moving tumors with and without dynamic multi-leaf collimator (DMLC) tracking.

Experiments were performed on a linear accelerator connected to prototype DMLC tracking software. A three-axis motion stage reproduced eight clinical tumor trajectories. For each trajectory, two VMAT treatment plans (low and high modulation) were delivered with and without DMLC tracking. Dose distributions were measured at 72 Hz using a biplanar dosimeter. Offline, the time-resolved doses were reconstructed by a novel simplified dose algorithm and compared to the measured doses by absolute dose differences.

The reconstructed doses were in good agreement with the measured doses of transient (2.5% mean absolute dose difference), cumulative (2.8%) and final accumulated doses (4.7%). The mean computation time for the dose calculation was 42.9 ms, making the algorithm feasible for online use.

Ongoing work focuses on online implementation of the developed algorithm, which may be used for treatment intervention in case of erroneous dose evolvement during both tracking and non-tracking treatments, or even on-the-fly dose repair if dose errors exist. The method described is applicable to standard therapeutic linear accelerators available worldwide.

O04.05 Henriette Bjerregaard

SUBSTRATE-INDUCED CONFORMATION OF THE HUMAN SEROTONIN TRANSPORTER

H. Bjerregaard, K. Severinsen, O. Wiborg, S. Sinning

Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University Hospital, Risskov

The human serotonin transporter (hSERT) regulates serotonergic signaling in the brain by actively regulating the concentration of serotonin in the

synaptic cleft. hSERT mediates reuptake of serotonin into the pre-synaptic neurons. hSERT is a molecular target for antidepressant drugs and

psychostimulants that act by altering the serotonin concentration in the 58

synapses.

Conformational changes of hSERT occur during substrate and ligand binding and during translocation of serotonin. Overall, during the transport cycle, hSERT shifts from an extracellular-facing conformation through an occluded state ending in a cytoplasmic-facing conformation.

A bound ligand in a fixed concentration induces a given conformation of hSERT. It has previously been shown that the substrate serotonin and the hallucinogenic alkaloid ibogaine both bind to hSERT and stabilize an inward-facing conformation of hSERT. However, the interplay between ligand binding, substrate transport, and hSERT conformation is not fully understood.

We have analyzed binding characteristics of the substrate serotonin and its effect on conformation of hSERT using the Substituted Cysteine Accessibility Method. Surprisingly, in a high-affinity state for serotonin binding, the substrate induces an outward-facing conformation of hSERT, which is found to be ion-dependent. This novel dualistic nature of substrate and the resulting conformational state might represent a hitherto undescribed step of the transport cycle.

O04.06 Anne Højland INVESTIGATING SORLA MEDIATED TRAFFICKING IN POLARIZED CELLS A. Højland, S. Christensen-Klinger, M. Nielsen

The Lundbeck Foundation MIND Center, Department of Biomedicine, Aarhus University Ole Worms Allé 1170-126 DK-8000 Aarhus C

SorLA belongs to the vps10p domain receptor family. This receptor family is multifunctional and highly expressed in the nervous system, where they have been implicated in Alzheimer's disease and injury-related neuronal cell death.

It has been shown that sorLA is involved in regulating the level of lipoprotein-lipase (LPL) in transfected fibroblast and in primary neurons.

Therefore, it is likely that this mechanism is important for the release of the vps10p receptor family ligands, among others, LPL.

Recent studies indicate that sorLA is involved in asymmetrical transport in polarized cell lines and may be a key factor in the transycosis across different types of epithelial and endothelial cells, among these, the Blood-Brain-Barrier and the endothelial cells of the arteries.

Thus, sorLA is likely to be of physical importance in regulating the level of LPL in the brain and systemic circulation.

Using the polarized kidney-epithelial derived cell line MDCK, the cellular localization and trafficking of sorLA has been further investigated. The motifs involved in the localization are also explored by use of chimera and mutated sorLA constructs. The methods used in these investigations are primarily immunocytochemistry and confocal imaging.

The study will also include identification of adaptor proteins involved in the transport as well as an investigation of sorLA-mediated transcytosis.

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