Interrater agreement of contouring of the neurovascular bundles and internal pudendal arteries in neurovascular-sparing magnetic resonance-guided radiotherapy for localized prostate cancer.

BACKGROUND AND PURPOSE: Radiation damage to neural and vascular tissue, such as the neurovascular bundles (NVBs) and internal pudendal arteries (IPAs), during radiotherapy for prostate cancer (PCa) may cause erectile dysfunction. Neurovascular-sparing magnetic resonance-guided adaptive radiotherapy (MRgRT) aims to preserve erectile function after treatment. However, the NVBs and IPAs are not routinely contoured in current radiotherapy practice. Before neurovascular-sparing MRgRT for PCa can be implemented, the interrater agreement of the contouring of the NVBs and IPAs on pre-treatment MRI needs to be assessed. MATERIALS AND METHODS: Four radiation oncologists independently contoured the prostate, NVB, and IPA in an unselected consecutive series of 15 PCa patients, on pre-treatment MRI. Dice similarity coefficients (DSCs) for pairwise interrater agreement of contours were calculated. Additionally, the DCS of a subset of the inferior half of the NVB contours (i.e. approximately prostate midgland to apex level) was calculated. RESULTS: Median overall interrater DSC for the left and right NVB was 0.60 (IQR: 0.54 - 0.68) and 0.61 (IQR: 0.53 - 0.69) respectively and for the left and right IPA 0.59 (IQR: 0.53 - 0.64) and 0.59 (IQR: 0.52 - 0.64) respectively. Median overall interrater DSC for the inferior half of the left NVB was 0.67 (IQR: 0.58 - 0.74) and 0.67 (IQR: 0.61 - 0.71) for the right NVB. CONCLUSION: We found that the interrater agreement for the contouring of the NVB and IPA improved with enhancement of the MRI sequence as well as further training of the raters. The agreement was best in the subset of the inferior half of the NVB, where a good agreement is clinically most relevant for neurovascular-sparing MRgRT for PCa.

Geometrical imaging accuracy, image quality and plan quality for prostate cancer treatments on a 1.5 T MRLinac in patients with a unilateral hip implant.

Purpose.To assess the feasibility of prostate cancer radiotherapy for patients with a hip implant on an 1.5 T MRI-Linac (MRL) in terms of geometrical image accuracy, image quality, and plan quality.Methods.Pretreatment MRI images on a 1.5 T MRL and 3 T MRI consisting of a T2-weighted 3D delineation scan and main magnetic field homogeneity (B0) scan were performed in six patients with a unilateral hip implant. System specific geometrical errors due to gradient nonlinearity were determined for the MRL. Within the prostate and skin contour,B0inhomogeneity, gradient nonlinearity error and the total geometrical error (vector summation of the prior two) was determined. Image quality was determined by visually scoring the extent of implant-born image artifacts. A treatment planning study was performed on five patients to quantify the impact of the implant on plan quality, in which conventional MRL IMRT plans were created, as well as plans which avoid radiation through the left or right femur.Results.The total maximum geometrical error in the prostate was <1 mm and the skin contour <1.7 mm; in all cases the machine-specific gradient error was most dominant. TheB0error for the MRlinac MRI could partly be predicted based on the pre-treatment 3 T scan. Image quality for all patients was sufficient at 1.5 T MRL. Plan comparison showed that, even with avoidance of the hips, in all cases sufficient target coverage could be obtained with similar D1cc and D5cc to rectum and bladder, while V28Gy was slightly poorer in only the rectum for femur avoidance.Conclusion.We showed that geometrical accuracy, image quality and plan quality for six prostate patients with a hip implant or hip fixation treated on a 1.5 T MRL did not show relevant deterioration for the used image settings, which allowed safe treatment.

Seminal vesicle intrafraction motion during the delivery of radiotherapy sessions on a 1.5 T MR-Linac.

PURPOSE: To evaluate seminal vesicle (SV) intrafraction motion using cinematic magnetic resonance imaging (cine-MR) during the delivery of online adaptive MR-Linac radiotherapy fractions, in preparation of MR-guided extremely hypofractionated radiotherapy for intermediate to high-risk prostate cancer patients. MATERIAL AND METHODS: Fifty prostate cancer patients were treated with 5 × 7.25 Gy on a 1.5 Tesla MR-Linac. 3D Cine-MR imaging was started simultaneously and acquired over the full beam-on period. Intrafraction motion in this cine-MR was determined for each SV separately with a previously validated soft-tissue contrast-based tracking algorithm. Motion statistics and coverage probability for the SVs and prostate were determined based on the obtained results. RESULTS: SV motion was automatically determined during the beam-on period (approx. 10 min) for 247 fractions. SV intrafraction motion shows larger spread than prostate intrafraction motion and increases over time. This difference is especially evident in the anterior and cranial translation directions. Significant difference in rotation about the left-right axis was found, with larger rotation for the SVs than the prostate. Intra-fraction coverage probability of 99% can be achieved when using 5 mm isometric expansion for the left and right SV and 3 mm for the prostate. CONCLUSION: This is the first study to investigate SV intrafraction motion during MR-guided RT sessions on an MR-Linac. We have shown that high quality 3D cine-MR imaging and SV tracking during RT is feasible with beam-on. The tracking method as described may be used as input for a fast replanning algorithm, which allows for intrafraction plan adaptation.

Anatomically-adaptive multi-modal image registration for image-guided external-beam radiotherapy.

Image-guided radiotherapy (IGRT) allows observation of the location and shape of the tumor and organs-at-risk (OAR) over the course of a radiation cancer treatment. Such information may in turn be used for reducing geometric uncertainties during therapeutic planning, dose delivery and response assessment. However, given the multiple imaging modalities and/or contrasts potentially included within the imaging protocol over the course of the treatment, the current manual approach to determining tissue displacement may become time-consuming and error prone. In this context, variational multi-modal deformable image registration (DIR) algorithms allow automatic estimation of tumor and OAR deformations across the acquired images. In addition, they require short computational times and a low number of input parameters, which is particularly beneficial for online adaptive applications, which require on-the-fly adaptions with the patient on the treatment table. However, the majority of such DIR algorithms assume that all structures across the entire field-of-view (FOV) undergo a similar deformation pattern. Given that various anatomical structures may behave considerably different, this may lead to the estimation of anatomically implausible deformations at some locations, thus limiting their validity. Therefore, in this paper we propose an anatomically-adaptive variational multi-modal DIR algorithm, which employs a regionalized registration model in accordance with the local underlying anatomy. The algorithm was compared against two existing methods which employ global assumptions on the estimated deformations patterns. Compared to the existing approaches, the proposed method has demonstrated an improved anatomical plausibility of the estimated deformations over the entire FOV as well as displaying overall higher accuracy. Moreover, despite the more complex registration model, the proposed approach is very fast and thus suitable for online scenarios. Therefore, future adaptive IGRT workflows may benefit from an anatomically-adaptive registration model for precise contour propagation and dose accumulation, in areas showcasing considerable variations in anatomical properties.

Prostate intrafraction motion during the preparation and delivery of MR-guided radiotherapy sessions on a 1.5T MR-Linac.

PURPOSE: To evaluate prostate intrafraction motion using MRI during the full course of online adaptive MR-Linac radiotherapy (RT) fractions, in preparation of MR-guided extremely hypofractionated RT. MATERIAL AND METHODS: Five low and intermediate risk prostate cancer patients were treated with 20 × 3.1 Gy fractions on a 1.5T MR-Linac. Each fraction, initial MRI (Pre) scans were obtained at the start of every treatment session. Pre-treatment planning MRI contours were propagated and adapted to this Pre scan after which plan re-optimization was started in the treatment planning system followed by dose delivery. 3D Cine-MR imaging was started simultaneously with beam-on and acquired over the full beam-on period. Prostate intrafraction motion in this cine-MR was determined with a previously validated soft-tissue contrast based tracking algorithm. In addition, absolute accuracy of the method was determined using a 4D phantom. RESULTS: Prostate motion was completely automatically determined over the full on-couch period (approx. 45 min) with no identified mis-registrations. The translation 95% confidence intervals are within clinically applied margins of 5 mm, and plan adaption for intrafraction motion was required in only 4 out of 100 fractions. CONCLUSION: This is the first study to investigate prostate intrafraction motions during entire MR-guided RT sessions on an MR-Linac. We have shown that high quality 3D cine-MR imaging and prostate tracking during RT is feasible with beam-on. The clinically applied margins of 5 mm have proven to be sufficient for these treatments and may potentially be further reduced using intrafraction plan adaptation guided by cine-MR imaging.

[Three estimations of the outflow of orthodontists from the field]. / Drie schattingen van de uitstroom van orthodontisten uit het vak.

The outflow of orthodontists through retirement is an important factor in the estimation of the required training capacity for this group of professionals. From 2002 through 2018, studies of the professional activity and retirement plans of orthodontists age 55 and older have been conducted fairly frequently, the most recent one dating from 2018. Based on the findings of these surveys, 3 estimations were obtained of the outflow through retirement. These were based on answers in earlier editions, the answers of their contemporaries and on the basis of the legal retirement age in the Netherlands. The number of active orthodontists in 2018 age 55 or older is estimated respectively to be 117, 116 and 102; according to all estimations, they will have retired in 2030. The estimations predict, respectively 56, 57 and 30 orthodontists will retire before 2023. According to 2 of the estimations, the outflow of orthodontists from the field will exceed the inflow from the universities in the coming years. The present training capacity in the Netherlands is not sufficient to compensate for the outflow of the first 2 estimations.

Dosimetric impact of soft-tissue based intrafraction motion from 3D cine-MR in prostate SBRT.

To investigate the dosimetric impact of intrafraction translation and rotation motion of the prostate, as extracted from daily acquired post-treatment 3D cine-MR based on soft-tissue contrast, in extremely hypofractionated (SBRT) prostate patients. Accurate dose reconstruction is performed by using a prostate intrafraction motion trace which is obtained with a soft-tissue based rigid registration method on 3D cine-MR dynamics with a temporal resolution of 11 s. The recorded motion of each time-point was applied to the planning CT, resulting in the respective dynamic volume used for dose calculation. For each treatment fraction, the treatment delivery record was generated by proportionally splitting the plan into 11 s intervals based on the delivered monitor units. For each fraction the doses of all partial plan/dynamic volume combinations were calculated and were summed to lead to the motion-affected fraction dose. Finally, for each patient the five fraction doses were summed, yielding the total treatment dose. Both daily and total doses were compared to the original reference dose of the respective patient to assess the impact of the intrafraction motion. Depending on the underlying motion of the prostate, different types of motion-affected dose distributions were observed. The planning target volumes (PTVs) ensured CTV_30 (seminal vesicles) D99% coverage for all patients, CTV_35 (prostate corpus) coverage for 97% of the patients and GTV_50 (local boost) for 83% of the patients when compared against the strict planning target D99% value. The dosimetric impact due to prostate intrafraction motion in extremely hypofractionated treatments was determined. The presented study is an essential step towards establishing the actual delivered dose to the patient during radiotherapy fractions.

Fast contour propagation for MR-guided prostate radiotherapy using convolutional neural networks.

PURPOSE: To quickly and automatically propagate organ contours from pretreatment to fraction images in magnetic resonance (MR)-guided prostate external-beam radiotherapy. METHODS: Five prostate cancer patients underwent 20 fractions of image-guided external-beam radiotherapy on a 1.5 T MR-Linac system. For each patient, a pretreatment T2-weighted three-dimensional (3D) MR imaging (MRI) scan was used to delineate the clinical target volume (CTV) contours. The same scan was repeated during each fraction, with the CTV contour being manually adapted if necessary. A convolutional neural network (CNN) was trained for combined image registration and contour propagation. The network estimated the propagated contour and a deformation field between the two input images. The training set consisted of a synthetically generated ground truth of randomly deformed images and prostate segmentations. We performed a leave-one-out cross-validation on the five patients and propagated the prostate segmentations from the pretreatment to the fraction scans. Three variants of the CNN, aimed at investigating supervision based on optimizing segmentation overlap, optimizing the registration, and a combination of the two were compared to results of the open-source deformable registration software package Elastix. RESULTS: The neural networks trained on segmentation overlap or the combined objective achieved significantly better Hausdorff distances between predicted and ground truth contours than Elastix, at the much faster registration speed of 0.5 s. The CNN variant trained to optimize both the prostate overlap and deformation field, and the variant trained to only maximize the prostate overlap, produced the best propagation results. CONCLUSIONS: A CNN trained on maximizing prostate overlap and minimizing registration errors provides a fast and accurate method for deformable contour propagation for prostate MR-guided radiotherapy.

Soft-tissue prostate intrafraction motion tracking in 3D cine-MR for MR-guided radiotherapy.

To develop a method to automatically determine intrafraction motion of the prostate based on soft tissue contrast on 3D cine-magnetic resonance (MR) images with high spatial and temporal resolution. Twenty-nine patients who underwent prostate stereotactic body radiotherapy (SBRT), with four implanted cylindrical gold fiducial markers (FMs), had cine-MR imaging sessions after each of five weekly fractions. Each cine-MR session consisted of 55 sequentially obtained 3D data sets ('dynamics') and was acquired over an 11 s period, covering a total of 10 min. The prostate was delineated on the first dynamic of every dataset and this delineation was used as the starting position for the soft tissue tracking (SST). Each subsequent dynamic was rigidly aligned to the first dynamic, based on the contrast of the prostate. The obtained translation and rotation describes the intrafraction motion of the prostate. The algorithm was applied to 6270 dynamics over 114 scans of 29 patients and the results were validated by comparing to previously obtained fiducial marker tracking data of the same dataset. Our proposed tracking method was also retro-perspectively applied to cine-MR images acquired during MR-guided radiotherapy of our first prostate patient treated on the MR-Linac. The difference in the 3D translation results between the soft tissue and marker tracking was below 1 mm for 98.2% of the time. The mean translation at 10 min were X: 0.0 [Formula: see text] 0.8 mm, Y: 1.0 [Formula: see text] 1.8 mm and Z: [Formula: see text] mm. The mean rotation results at 10 min were X: [Formula: see text], Y: 0.1 [Formula: see text] 0.6° and Z: 0.0 [Formula: see text] 0.7°. A fast, robust and accurate SST algorithm was developed which obviates the need for FMs during MR-guided prostate radiotherapy. To our knowledge, this is the first data using full 3D cine-MR images for real-time soft tissue prostate tracking, which is validated against previously obtained marker tracking data.

Fiducial marker based intra-fraction motion assessment on cine-MR for MR-linac treatment of prostate cancer.

We have developed a method to determine intrafraction motion of the prostate through automatic fiducial marker (FM) tracking on 3D cine-magnetic resonance (MR) images with high spatial and temporal resolution. Twenty-nine patients undergoing prostate stereotactic body radiotherapy (SBRT), with four implanted cylindrical gold FMs, had cine-MR imaging sessions after each of five weekly fractions. Each cine-MR examination consisted of 55 sequentially obtained 3D datasets ('dynamics'), acquired over a 11 s period, covering a total of 10 min. FM locations in the first dynamic were manually identified by a clinician, FM centers in subsequent dynamics were automatically determined. Center of mass (COM) translations and rotations were determined by calculating the rigid transformations between the FM template of the first and subsequent dynamics. The algorithm was applied to 7315 dynamics over 133 scans of 29 patients and the obtained results were validated by comparing the COM locations recorded by the clinician at the halfway-dynamic (after 5 min) and end dynamic (after 10 min). The mean COM translations at 10 min were X: 0.0 [Formula: see text] 0.8 mm, Y: 1.0 [Formula: see text] 1.9 mm and Z: 0.9 [Formula: see text] 2.0 mm. The mean rotation results at 10 min were X: 0.1 [Formula: see text] 3.9°, Y: 0.0 [Formula: see text] 1.3° and Z: 0.1 [Formula: see text] 1.2°. The tracking success rate was 97.7% with a mean 3D COM error of 1.1 mm. We have developed a robust, fast and accurate FM tracking algorithm for cine-MR data, which allows for continuous monitoring of prostate motion during MR-guided radiotherapy (MRgRT). These results will be used to validate automatic prostate tracking based on soft-tissue contrast.

First patients treated with a 1.5 T MRI-Linac: clinical proof of concept of a high-precision, high-field MRI guided radiotherapy treatment.

The integration of 1.5 T MRI functionality with a radiotherapy linear accelerator (linac) has been pursued since 1999 by the UMC Utrecht in close collaboration with Elekta and Philips. The idea behind this integrated device is to offer unrivalled, online and real-time, soft-tissue visualization of the tumour and the surroundings for more precise radiation delivery. The proof of concept of this device was given in 2009 by demonstrating simultaneous irradiation and MR imaging on phantoms, since then the device has been further developed and commercialized by Elekta. The aim of this work is to demonstrate the clinical feasibility of online, high-precision, high-field MRI guidance of radiotherapy using the first clinical prototype MRI-Linac. Four patients with lumbar spine bone metastases were treated with a 3 or 5 beam step-and-shoot IMRT plan. The IMRT plan was created while the patient was on the treatment table and based on the online 1.5 T MR images; pre-treatment CT was deformably registered to the online MRI to obtain Hounsfield values. Bone metastases were chosen as the first site as these tumors can be clearly visualized on MRI and the surrounding spine bone can be detected on the integrated portal imager. This way the portal images served as an independent verification of the MRI based guidance to quantify the geometric precision of radiation delivery. Dosimetric accuracy was assessed post-treatment from phantom measurements with an ionization chamber and film. Absolute doses were found to be highly accurate, with deviations ranging from 0.0% to 1.7% in the isocenter. The geometrical, MRI based targeting as confirmed using portal images was better than 0.5 mm, ranging from 0.2 mm to 0.4 mm. In conclusion, high precision, high-field, 1.5 T MRI guided radiotherapy is clinically feasible.

Gate-Tunable Band Structure of the LaAlO_{3}-SrTiO_{3} Interface.

The two-dimensional electron system at the interface between LaAlO_{3} and SrTiO_{3} has several unique properties that can be tuned by an externally applied gate voltage. In this work, we show that this gate tunability extends to the effective band structure of the system. We combine a magnetotransport study on top-gated Hall bars with self-consistent Schrödinger-Poisson calculations and observe a Lifshitz transition at a density of 2.9×10^{13}cm^{-2}. Above the transition, the carrier density of one of the conducting bands decreases with increasing gate voltage. This surprising decrease is accurately reproduced in the calculations if electronic correlations are included. These results provide a clear, intuitive picture of the physics governing the electronic structure at complex-oxide interfaces.

Children's outcomes at 2-year follow-up after 4 years of structured multi-professional medical-ethical decision-making in a neonatal intensive care unit.

OBJECTIVE: We reviewed our decisions about continuation/withdrawal of life-sustaining treatments in a group of critically ill newborns who were discussed in structured medical ethical decision-making meetings, and provide the surviving children's outcomes at 2-year follow-up. STUDY DESIGN: In an explorative observational study, 61 cases were evaluated. The children involved had been discussed in such a structured way from 2009 to 2012 in a level III-D neonatal intensive care unit. RESULTS: Decisions made were: full treatment (n=6), earlier restriction cancelled (n=3), treatment restriction (n=30) and palliative care (n=22). Parents of six children disagreed with the decision proposed. Thirteen (54%) of the 24 children who survived (39%) had moderate to severe neurological problems; 8 (33%) had additional sequelae; only one 2-year-old child was healthy. CONCLUSIONS: Decisions made varied to a large extent. The poor outcomes should be disseminated among decision makers. Future studies must explore new ways to improve outcome prediction, extend follow-up periods and consider what living with severe handicaps really means for both child and family.

The Effect of Pivotal Response Treatment in Children with Autism Spectrum Disorders: A Non-randomized Study with a Blinded Outcome Measure.

Purpose of this quasi-experimental trial was to investigate the effect of Pivotal response treatment (PRT) versus treatment as usual (TAU) on autism symptoms. Children with autism spectrum disorder (ASD), aged 3-8 years, received either PRT (n = 11) or TAU (n = 13). Primary outcome measure was the total score on the Autism Diagnostic Observation Schedule at pre- and posttreatment. Additionally, general problem behavior and parental stress levels were measured. Children in the PRT condition improved on the primary outcome measure compared to the TAU group with a small effect size [partial η2 = 0.22 (95 % CI 0.00-0.46)]. Neither group demonstrated significant changes in the secondary outcomes. This study suggests that PRT may improve autism symptoms in children with ASD over TAU.

[Evidence-based clinical practice guidelines in oral care 3. Support for the development of clinical practice guidelines]. / Evidencebased klinische praktijkrichtlijnen in de mondzorg 3. Draagvlak voor richtlijnontwikkeling in de mondzorg.

Support is an important factor in the implementation of clinical practice guidelines. Data from 5 studies from 1998 through 2013 offer insight into the support for clinical practice guidelines among dentists, orthodontists, dental hygienists and denturists in the Netherlands. In these, attitudes, opinions, knowledge and behaviour were seen as indicators of support. Dentists have an increasingly positive attitude towards clinical practice guidelines. The majority is aware of and uses at least 1 of the guidelines available to them and are in favour of the development of clinical practice guidelines. Orthodontists and dental hygienists have available few such guidelines, but the majority of both groups favour their development. Among denturists, who also have little experience with clinical practice guidelines, there are fewer supporters for their development. All in all, among caregivers in oral healthcare in the Netherlands, support for the use and development of clinical practice guidelines is growing.

Microenvironment involved in FPR1 expression by human glioblastomas.

Formyl peptide receptor 1 (FPR1) activity in U87 glioblastoma (GBM) cells contributes to tumor cell motility. The present study aimed to evaluate the FPR1 expression in human GBM, the possibility to elicit agonist induced FPR1 activation of GBM cells and inhibit this activation with chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS). Immunohistochemistry was used to assess FPR1 expression in GBM patient samples, which was present in all 178 samples. Also FPR1 mRNA levels measured with quantitative PCR, could be detected in all 25 GBM patient samples tested. Activation of FPR1 in U87 cells, as measured by human mitochondrial-derived agonists, increased calcium mobilization, AKT and ERK1/2 phosphorylation, and ligand-induced migration. Inhibition of all responses could be achieved with CHIPS. Eight early passage human Groningen Glioma (GG) cell lines, isolated from primary GBM tissue were screened for the presence of FPR1. FPR1 mRNA and protein expression as well as receptor activation could not be detected in any of these early passage GG cell lines. However FPR1 was present in ex vivo tumors formed by the same GG cell lines after being implanted in mouse brains. FPR1 is highly expressed in human GBM specimens, it can be activated by human mitochondrial-derived agonists in U87 and inhibited with CHIPS. FPR1 cannot be detected in early passage GG cell lines in vitro, however when engrafted in the mouse brain these cells show FPR1 expression. These results suggest a role of the brain microenvironment in FPR1 expression in GBM.

[The Data Stations project: a monitor of dental practice in The Netherlands]. / Project Peilstations: monitor van de tandheelkundige beroepsuitoefening in Nederland.

Since 1995 the Dutch Dental Association (NMT) has carried out research on, in particular, the non-clinical aspects of dental practice with the Data Stations project. At present, within this research project 5 studies are conducted on a regular basis: the Dental Consumption Study, the Dental Practice Study, the Omnibus Survey, the Young Dentist Study and the Quality of Oral Care Study. From the results of this research project it appears that during the last decades dentists have increasingly been working cooperatively. This is expressed in dental practices with more dentists and more staff workers, with more dental chairs and more patients. The length of the working week, however, has changed very little over the years. Among both young people and adults gradual changes have taken place in dental consumption during the period 1997-2011. By intensifying the collaboration with clinical dental researchers the scope of the research within this project can be expanded to include the quality of oral care and the effects of care which has been provided on oral health in The Netherlands.

Inhibition of formyl peptide receptor in high-grade astrocytoma by CHemotaxis Inhibitory Protein of S. aureus.

BACKGROUND: High-grade astrocytomas are malignant brain tumours that infiltrate the surrounding brain tissue and have a poor prognosis. Activation of formyl peptide receptor (FPR1) on the human astrocytoma cell line U87 promotes cell motility, growth and angiogenesis. We therefore investigated the FPR1 inhibitor, Chemotaxis Inhibitory Protein of S. aureus (CHIPS), as a potential anti-astrocytoma drug. METHODS AND RESULTS: FPR1 expression was studied immunohistochemically in astrocytomas WHO grades I-IV. With intracellular calcium mobilisation and migration assays, human ligands were tested for their ability to activate FPR1 on U87 cells and on a cell line derived from primary astrocytoma grade IV patient material. Thereafter, we selectively inhibited these ligand-induced responses of FPR1 with an anti-inflammatory compound called Chemotaxis Inhibitory Protein of S. aureus (CHIPS). U87 xenografts in NOD-SCID mice served to investigate the effects of CHIPS in vivo. FPR1 was expressed in 29 out of 32 (90%) of all grades of astrocytomas. Two human mitochondrial-derived formylated peptides, formyl-methionil-leucine-lysine-isoleucine-valine (fMLKLIV) and formyl-methionil-methionil-tyrosine-alanine-leucine-phenylalanine (fMMYALF), were potent activators of FPR1 on tumour cells. Ligand-induced responses of FPR1-expressing tumour cells could be inhibited with FPR1 inhibitor CHIPS. Treatment of tumour-bearing mice with CHIPS slightly reduced tumour growth and improved survival as compared to non-treated animals (P=0.0019). CONCLUSION: Targeting FPR1 with CHIPS reduces cell motility and tumour cell activation, and prolongs the survival of tumour-bearing mice. This strategy could be explored in future research to improve treatment results for astrocytoma patients.

Integrated megavoltage portal imaging with a 1.5 T MRI linac.

In this note, the feasibility of complementing our hybrid 1.5 T MRI linac (MRL) with a megavoltage (MV) portal imager is investigated. A standard aSi MV detector panel is added to the system and both qualitative and quantitative performances are determined. Simultaneous MR imaging and transmission imaging can be performed without mutual interference. The MV image quality is compromised by beam transmission and longer isocentre distance; still, the field edges and bony anatomy can be detected at very low dose levels of 0.4 cGy. MV imaging integrated with the MRL provides an independent and well-established position verification tool, a field edge check and a calibration for alignment of the coordinate systems of the MRI and the accelerator. The portal imager can also be a valuable means for benchmarking MRI-guided position verification protocols on a patient-specific basis in the introductory phase.

[Recently graduated dentists: working situation and future plans]. / Werksituatie en toekomstplannen van recent afgestudeerde tandartsen.

The Dutch Dental Association (NMT) surveyed dentists who graduated in 2004, 2005 or 2006 concerning their work situation and plans for the future. They were also asked about their experiences at the start of their career In general, the recently graduated dentists did not face difficulties at the start of their professional life. Most dentists worked in the practice of a colleague, but the majority ultimately wanted to have their own practice. The latter applied more to men than women. Furthermore, there was a clear preference for working within a team and most of them planned to specialize in a specific branch of dentistry. The survey also revealed that the delegation of tasks to dental hygienists and prevention assistants was more or less taken for granted by recently graduated dentists.