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Background Rheumatoid arthritis (RA) predominantly affects women and is associated with hypertension and arterial stiffness. We explored factors associated with change in arterial stiffness in patients with RA treated with disease-modifying antirheumatic drug (DMARD) therapy.Methods Seventy-seven outpatients with RA (age 55 ± 11, 69% women), with indication for treatment with biological or targeted synthetic DMARDs, were included. Pulse wave velocity (PWV), augmentation pressure (AP), augmentation index (AIx) and Disease Activity Score in 28 joints (DAS28) were measured at baseline and after a mean of 22 months of follow-up.Results At follow-up, 83% used DMARDs and 73% had achieved remission or low disease activity. DAS28 decreased from 3.8 ± 1.3 to 2.8 ± 1.2 (p

Aims: To evaluate the effectiveness of personalized lifestyle intervention service for persons with Type 2 diabetes (T2D), implemented in a real-world setting at two Healthy Life Centers (HLC) in Norway., Methods: Persons with T2D were randomized into either an HLC intervention group or a usual care group for 12 weeks. All participants were screened using a questionnaire tool and had one initial patient-centred health conversation at the HLC. In the intervention group, participants chose interventions with support from HLC staff. The usual care group continued independently. Outcome variables were assessed at baseline, 12 weeks, and 24 weeks (if completing two interventions)., Results: 110 participants were included (mean age 59.9, 59 % T2D duration < 10 years, 36 % females). There was no significant difference in HbA1c change between intervention and usual care groups (mean difference -1.2 mmol/l, 95 % CI: -3.7 to 1.3, p = 0.33). HbA1c was significantly reduced in both groups (mean reduction 3.8 mmol/l (95 % CI: 2.1 to 5.5, p < 0.001) vs. 2.6 mmol/l (95 % CI: 0.7 to 4.4, p = 0.006), respectively)., Conclusions: Both the HLC personalized follow-up and usual care groups reduced HbA1c with no significant differences between groups. This suggests that low-threshold municipal healthcare can effectively support lifestyle changes in individuals with T2D., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

Background: The most appropriate treatment for men with prostate cancer and positive pelvic nodes, N+, is an area of active controversy. We report our 5-years outcomes in men with locally advanced prostate cancer (T1-T4N0-N1M0) treated with definitive radiotherapy encompassing the prostate and pelvic lymph nodes (intensity modulated radiotherapy, IMRT) and long-term androgen deprivation therapy (ADT)., Material and Methods: Of the 138 consecutive eligible men all living patients have been followed up to almost 5 years. Survival endpoints for 5-year biochemical failure-free survival (BFFS), relapse-free survival (RFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were assessed by Kaplan-Meier analysis. Univariate and multivariate Cox regression proportional hazards models were constructed for all survival endpoints. The RTOG morbidity grading system for physician rated toxicity was applied., Results: Patients with locally advanced T3-T4 tumors (35 %) and N1 (51 %) have favorable outcome when long-term ADT is combined with definitive radiotherapy encompassing pelvic lymph nodes. The 5-year BFFS, RFS, PCSS and OS were 71.4, 76.2, 94.5 and 89.0 %, respectively. High Gleason sum (9-10) had a strong independent prognostic impact on BFFS, RFS and OS (p = 0.001, <0.001, and 0.005 respectively). The duration of ADT (= > 28 months) showed a significant independent association with improved PCSS (p = 0.02) and OS (p = 0.001). Lymph node involvement was not associated with survival endpoints in the multivariate analysis. The radiotherapy induced toxicity seen in our study population was moderate with rare Grade 3 GI side effects and up to 11 % for Grade 3 GU consisting mainly of urgency and frequency., Conclusion: Pelvic IMRT in combination with long-term ADT can achieve long-lasting disease control in men with N+ disease and unfavorable prognostic factors.

Background: Dose painting by numbers (DPBN) is a method to deliver an inhomogeneous tumor dose voxel-by-voxel with a prescription based on biological medical images. However, planning of DPBN is not supported by commercial treatment planning systems (TPS) today. Here, a straightforward method for DPBN with a standard TPS is presented., Material and Methods: DPBN tumor dose prescription maps were generated from (18)F-FDG-PET images applying a linear relationship between image voxel value and dose. An inverted DPBN prescription map was created and imported into a standard TPS where it was defined as a mock pre-treated dose. Using inverse optimization for the summed dose, a planned DPBN dose distribution was created. The procedure was tested in standard TPS for three different tumor cases; cervix, lung and head and neck. The treatment plans were compared to the prescribed DPBN dose distribution by three-dimensional (3D) gamma analysis and quality factors (QFs). Delivery of the DPBN plans was assessed with portal dosimetry (PD)., Results: Maximum tumor doses of 149%, 140% and 151% relative to the minimum tumor dose were prescribed for the cervix, lung and head and neck case, respectively. DPBN distributions were well achieved within the tumor whilst normal tissue doses were within constraints. Generally, high gamma pass rates (> 89% at 2%/2 mm) and low QFs (< 2.6%) were found. PD showed that all DPBN plans could be successfully delivered., Conclusions: The presented methodology enables the use of currently available TPSs for DPBN planning and delivery and may therefore pave the way for clinical implementation.

Biological aging alters the metabolism and volume of adipose tissue depots. Recent evidence suggests that circadian mechanisms play a role in promoting adipogenesis, obesity, and lipodystrophy. The current study compared cohorts of younger (5-9 months) and older (24-28 months) C57BL/6 mice as a function of biological age and circadian time. Advanced age significantly reduced the weight of the brown, epididymal, inguinal, and retroperitoneal adipose depots but not total body weight. The older mice reduced their physical activity by >50% and delayed their activity initiation after light offset. The expressed transcriptome in brown and white adipose depots and liver of both cohorts displayed evidence of circadian rhythmicity; however, the oscillating mRNAs differed significantly between age groups and across tissues. The amplitude of Cry1, a component of the negative arm of the circadian apparatus, and downstream regulators such as Rev-erbα were elevated in the older relative to the younger cohorts as a function of circadian time. Overall, transcript levels differed significantly for 557 (inguinal adipose), 1,016 (liver), and 1,021 (brown adipose) expressed sequences between the cohorts as a function of age. These included transcripts encoding proteins within the canonical and non-canonical Wnt pathways. Since the Wnt pathway regulates adipose stem cell differentiation and shares a critical enzyme, glycogen synthase kinase 3β, with the circadian mechanism, the intersection between these two fundamental regulatory mechanisms merits further investigation with respect to biological aging of adipose tissues.

Introduction: Our primary aim was to make a phantom for PET that could mimic a highly irregular tumour and provide true tumour contours. The secondary aim was to use the phantom to assess the accuracy of different methods for delineation of tumour volume from the PET images., Material and Methods: An empty mould was produced on the basis of a contrast enhanced computed tomography (CT) study of a patient with a squamous cell carcinoma in the head and neck region. The mould was filled with a homogeneous fast-settling gel that contained both (18)F for positron emission tomography (PET) and an iodine contrast agent. This phantom (mould and gel) was scanned on a PET/CT scanner. A series of reference tumour contours were obtained from the CT images in the PET/CT. Tumour delineation based on the PET images was achieved manually, by isoSUV thresholding, and by a recently developed three-dimensional (3D) Difference of Gaussians algorithm (DoG). Average distances between the PET-derived and reference contours were assessed by a 3D distance transform., Results: The manual, thresholding and DoG delineation methods resulted in volumes that were 146%, 86% and 100% of the reference volume, respectively, and average distance deviations from the reference surface were 1.57 mm, 1.48 mm and 1.0, mm, respectively., Discussion: Manual drawing as well as isoSUV determination of tumour contours in geometrically irregular tumours may be unreliable. The DoG method may contribute to more correct delineation of the tumour. Although the present phantom had a homogeneous distribution of activity, it may also provide useful knowledge in the case of inhomogeneous activity distributions., Conclusion: The geometric irregular tumour phantom with its inherent reference contours was an important tool for testing of different delineation methods and for teaching delineation.

Somatic cell nuclear transfer (SCNT), the technique commonly known as cloning, permits transformation of a somatic cell into an undifferentiated zygote with the potential to develop into a newborn animal (i.e., a clone). In somatic cells, chromatin is programmed to repress most genes and express some, depending on the tissue. It is evident that the enucleated oocyte provides the environment in which embryonic genes in a somatic cell can be expressed. This process is controlled by a series of epigenetic modifications, generally referred to as "nuclear reprogramming," which are thought to involve the removal of reversible epigenetic changes acquired during cell differentiation. A similar process is thought to occur by overexpression of key transcription factors to generate induced pluripotent stem cells (iPSCs), bypassing the need for SCNT. Despite its obvious scientific and medical importance, and the great number of studies addressing the subject, the molecular basis of reprogramming in both reprogramming strategies is largely unknown. The present review focuses on the cellular and molecular events that occur during nuclear reprogramming in the context of SCNT and the various approaches currently being used to improve nuclear reprogramming. A better understanding of the reprogramming mechanism will have a direct impact on the efficiency of current SCNT procedures, as well as iPSC derivation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The combination of paclitaxel (PTX) and topoisomerase I inhibitors such as camptothecin (CPT) constitutes a therapeutic strategy based on anticipated synergism. However, previous in vitro studies have generated contradictory findings for this strategy. The interaction between these drugs can be synergistic or antagonistic, depending on the cell type examined. To gain additional insight into this promising yet controversial strategy, we investigated the interaction between PTX and CPT in three different cell lines (PANC-1, MDA-MB-231 and HL-60) and explored possible underlying mechanisms of synergy or antagonism. Using a novel solubilizing natural compound, rubusoside, water-insoluble PTX and CPT were solubilized to enable the comparison of the effects of single drugs and their combination on cell viability. Intracellular drug concentrations were quantified to examine the effect of CPT on cellular uptake and accumulation of PTX. Flow cytometry and quantitative real-time PCR gene array analyses were used to explore the mechanisms behind the interaction between PTX and CPT. Our studies confirmed that rubusoside-solubilized PTX or CPT maintained cytotoxicity, causing significant reductions in cell viability. However, the efficacy of the combination of PTX and CPT produced varied results based on the cell line tested. CPT antagonistically reduced the cytotoxic activity of PTX in PANC-1 and MDA-MB-231 cells. The effect of CPT on the cytotoxicity of PTX was less pronounced in HL-60 cells, showing neither synergy nor antagonism. Analysis of apoptosis by flow cytometry revealed that upon co-treatment with CPT, apoptosis induced by PTX was attenuated in PANC-1 and MDA-MB-231 cells. In agreement with our cytotoxicity findings, no synergistic or antagonistic effects on apoptosis were observed in HL-60 cells. The antagonism in PANC-1 and MDA-MB-231 cells was not a result of reduced PTX uptake and accumulation because the amount of intracellular PTX was not altered upon co-treatment with CPT. Moreover, higher expression of anti-apoptosis-related transcripts (BCL2L10, CFLAR, HIP1 and TRADD) in PANC-1 cells was observed upon combination treatment over PTX treatment alone. Although exact underlying mechanisms are unknown, the suspected CPT-dependent reduction of intracellular PTX accumulation was ruled out. The findings of antagonism and increased anti-apoptotic gene transcription serve as a precaution to the design of combination drug strategies where a synergistic interaction may not exist.

Cone beam CT (CBCT) imaging has become an integral part of radiation therapy, with images typically used for offline or online patient setup corrections based on bony anatomy co-registration. Ideally, the co-registration should be based on tumor localization. However, soft tissue contrast in CBCT images may be limited. In the present work, contrast enhanced CBCT (CECBCT) images were used for tumor visualization and treatment adaptation. Material and methods. A spontaneous canine maxillary tumor was subjected to repeated cone beam CT imaging during fractionated radiotherapy (10 fractions in total). At five of the treatment fractions, CECBCT images, employing an iodinated contrast agent, were acquired, as well as pre-contrast CBCT images. The tumor was clearly visible in post-contrast minus pre-contrast subtraction images, and these contrast images were used to delineate gross tumor volumes. IMRT dose plans were subsequently generated. Four different strategies were explored: 1) fully adapted planning based on each CECBCT image series, 2) planning based on images acquired at the first treatment fraction and patient repositioning following bony anatomy co-registration, 3) as for 2), but with patient repositioning based on co-registering contrast images, and 4) a strategy with no patient repositioning or treatment adaptation. The equivalent uniform dose (EUD) and tumor control probability (TCP) calculations to estimate treatment outcome for each strategy. Results. Similar translation vectors were found when bony anatomy and contrast enhancement co-registration were compared. Strategy 1 gave EUDs closest to the prescription dose and the highest TCP. Strategies 2 and 3 gave EUDs and TCPs close to that of strategy 1, with strategy 3 being slightly better than strategy 2. Even greater benefits from strategies 1 and 3 are expected with increasing tumor movement or deformation during treatment. The non-adaptive strategy 4 was clearly inferior to all three adaptive strategies. Conclusion. CECBCT may prove useful for adaptive radiotherapy.

The performance of 3 multileaf collimator (MLC) systems (Varian Medical Systems, Elekta, and Siemens Medical Solutions) mounted on 7 different radiotherapy linear accelerators was investigated by a stripe test. The stripe test consisted of 8 adjacent multileaf segments of 2.5 x 40 cm(2), enclosed by all leaf pairs. With 6-MV photons, the segments were used to irradiate Agfa CR films. The optical density profile of the irradiated film in the travel direction of the MLC was used to estimate the short- and long-term leaf positioning reproducibility. The short-term reproducibility was found by analyzing 6 consecutive stripe tests. The long-term reproducibility was obtained by performing 3 to 5 stripe tests over 2 months. The short-term reproducibility was mainly within 0.3 mm for all systems. For the long-term reproducibility, the Varian and Elekta MLCs were within 0.4 to 0.5 mm, while the Siemens MLC showed a wider distribution, with values up to 1 mm for some leaf pairs. The inferior long-term reproducibility of the Siemens MLCs was mainly due to a decrease of the segment size with time. In conclusion, the stripe test is a useful method for evaluating MLC performance. Furthermore, the long-term reproducibility varied among the MLC systems investigated.

Objective: To describe fertility issues, only rarely discussed with patients with prostate cancer, although paternity after treatment might be an important component of quality of life for some, as exemplified by two of our patients., Patients: During pretreatment counselling two patients with newly diagnosed prostate cancer initiated the discussion of paternity after treatment. Patient 1 then opted for radiotherapy as the treatment least likely to damage fertility, whereas patient 2 had semen cryopreservation before external beam radiotherapy combined with 6 months adjuvant hormone treatment., Results: Patient 1 became a father to a healthy child 9 months after starting radiotherapy, with conception two days after he had received one session of brachytherapy with (192)Ir (total dose 10 Gy, testicular dose, 0.1 Gy). Patient 2 fathered a child 36 months after completing external beam radiotherapy (total dose 74 Gy, testicular dose 1.2-2.3 Gy), which was combined with medical castration of 6 months' duration., Conclusion: Fertility issues should be considered in patients before curative treatment of prostate cancer.

Purpose: To present a methodology to estimate optimal treatment margins for radiotherapy of prostate cancer based on interfraction imaging., Materials and Methods: Cone beam CT images of a prostate cancer patient undergoing fractionated radiotherapy were acquired at all treatment sessions. The clinical target volume (CTV) and organs at risk (OARs; bladder and rectum) were delineated in the images. Random sampling from the CTV-OAR library was performed in order to simulate fractionated radiotherapy including intra- and interpatient variability in setup and organ motion/deformation. For each simulated patient, four treatment fields defined by multileaf collimators were automatically generated around the planning CTV. The treatment margin (the distance from the CTV to the field border) was varied between 2.5 and 20 mm. Resulting dose distributions were calculated by a convolution method. Doses to OARs were reconstructed by polynomial warping, while the CTV was assumed to be a rigid body. The equivalent uniform dose (EUD), the tumor control probability (TCP) and the normal tissue complication probability (NTCP) were used to estimate the clinical effect. Patient repositioning strategies at treatment were compared., Results: The simulations produced population based EUD histograms for the CTV and the OARs. The number of patients receiving an optimal target EUD increased with increasing margins, but at the cost of an increasing number receiving a high EUD to the OARs. Calculations of the probability of complication-free tumor control and subsequent analysis gave an optimal treatment margin of about 10mm for the simulated population, if no correction strategy was undertaken., Conclusions: The current work illustrates the principle of optimal treatment margins based on interfraction imaging. Clinically applicable margins may be obtained if a large patient image database is available.

Background: The advantage of MRI-based radiotherapy planning is the superior soft tissue differentiation. However, for accurate patient dose calculations, a conversion of the MR images into Hounsfield CT maps is necessary. The aim of the present study was to investigate the dose accuracy that can be achieved with segmented MR-images derived from the planning CT images by assigning fixed densities to different classes of tissues., Methods: Treatment plans for ten prostate cancer patients were selected. A collapsed cone algorithm was used to calculate patient dose distributions. The dose calculations were based on four different image sets: (1) the original CT-series (DD(DP)), (2) a simulated MR series with all tissue set to a homogenous water equivalent material of density 1.02 g/cm(3) (DD(W)), (3) a simulated MR series with soft tissue set to a water equivalent material with density 1.02 g/cm(3) and the bone set to a density of 1.3 g/cm(3) (DD(W+B1.3)), and (4) a simulated MR series identical to (3) but with a bone density equal to 2.1 g/cm(3) (DD(W+B2.1)). The dose distributions were compared by analysing dose difference histograms as well as through a visual display of spatial dose deviations., Results: The population based minimum, mean and maximum dose difference between the DD(DP) and DD(W) in the target volume was -2.8, -1.0 and 0.6%, respectively. Corresponding differences between DD(DP) and DD(W+B1.3) were -1.6, 0.2 and 1.5%, respectively, and between DD(DP) and DD(W+B2.1) -4.3, 4.2 and 9.7%, respectively. For the rectum, the differences between CT(DP) and the other image sets were in the range of -19.5 to 8.8%. For the bladder, the differences were in the range of -9.6 to 7.0%., Conclusions: A systematic study using segmented MR images was undertaken. To achieve an acceptable accuracy in the CTV dose, the MR images should be segmented into bone and water equivalent tissue. Still, significant dose deviation for the organs at risk may be present. As tissue segmentation in real MR images is introduced, segmentation errors and errors that stem from geometrical non-linearities may further reduce the accuracy.

IMRT treatments using multi-leaf collimators may involve a large number of segments in order to spare the organs at risk. When a large proportion of these segments are small, leaf positioning errors may become relevant and have therapeutic consequences. The performance of four head and neck IMRT treatments under eight different cases of leaf positioning errors has been studied. Systematic leaf pair offset errors in the range of +/-2.0 mm were introduced, thus modifying the segment sizes of the original IMRT plans. Thirty-six films were irradiated with the original and modified segments. The dose difference and the gamma index (with 2%/2 mm criteria) were used for evaluating the discrepancies between the irradiated films. The median dose differences were linearly related to the simulated leaf pair errors. In the worst case, a 2.0 mm error generated a median dose difference of 1.5%. Following the gamma analysis, two out of the 32 modified plans were not acceptable. In conclusion, small systematic leaf bank positioning errors have a measurable impact on the delivered dose and may have consequences for the therapeutic outcome of IMRT.

Two different commercial electronic portal imaging devices (EPIDs), one based on a liquid ion chamber matrix and the other based on a fluoroscopic CCD camera, were used to acquire readings that, through a calibration procedure, provided images proportional to the absolute dose to a virtual water slab located at the EPID plane. The transformation of the matrix ion chamber image into a portal dose image (PDI) was based on a published relationship between dose rate and ionization current. For the fluoroscopic CCD-camera-based system, the transformation was based on a deconvolution with a radial light scatter kernel. Local response variations were corrected in the images from both systems using open field fluence maps. The acquired PDIs were compared with PDIs calculated with the collapsed cone superposition method for a three-dimensional detector model in water equivalent buildup material. The calculation model was based on the beam modelling and geometrical description of the treatment unit and energy used for treatment planning in a kernel-based system. The validity of the calculation method was evaluated for several field shapes and thicknesses of patient phantoms for the matrix ion chamber at 6 MV x-rays and for the camera-based EPID at 6 and 15 MV x-rays. The agreement between predicted and measured PDIs was evaluated with dose comparisons at points of interest and gamma index calculations. The average area failing the passing criteria in dose and position deviation was analysed to validate the performance of the method. For the matrix ion chamber on average an area less than 1% fails the passing criteria of 3 mm and 3%. For the camera-based EPID, the average area is 7% and 1% for 6 and 15 MV, respectively. The overall agreement centrally in the fields was 0.1 +/- 1.6% (1 sd) for the camera-based EPID and -0.1 +/- 1.6% (1 sd) for the matrix ion chamber. Thus, an absolute dose calibrated EPID could validate the delivered dose to the patient by comparing a calculated and a measured PDI.

Locally adaptive image binarization with a sliding-window threshold can be an effective tool for various image processing tasks. We have used the method for the detection of bone ridges in radiotherapy portal images. However, a straight-forward implementation of sliding-window processing is too time consuming for routine use. Therefore, we have developed a new thresholding criterion suitable for incremental update within the sliding window, and we show that our algorithm gives better results on difficult portal images than various publicly available adaptive thresholding routines. For small windows, the routine is also faster than an adaptive implementation of the Otsu algorithm that uses interpolation between fixed tiles, and the resulting images are equally good.

A bovine artificial chromosome (BAC) library of 105 984 clones has been constructed in the vector pBeloBAC11 and organized in 3-dimension pools and high density membranes for screening by PCR and hybridization. The average insert size, determined after analysis of 388 clones, was estimated at 120 kb corresponding to a four genome coverage. Given the fact that a male was used to construct the library, the probability of finding any given autosomal and X or Y locus is respectively 0.98 and 0.86. The library was screened for 164 microsatellite markers and an average of 3.9 superpools was positive for each PCR system. None of the 50 or so BAC clones analysed by FISH was chimeric. This BAC library increases the international genome coverage for cattle to around 28 genome equivalents and extends the coverage of the ruminant genomes available at the Inra resource center to 15 genome equivalents.

Here we describe a procedure for cloning pigs by the use of in vitro culture systems. Four healthy male piglets from two litters were born following nuclear transfer of cultured somatic cells and subsequent embryo transfer. The initiation of five additional pregnancies demonstrates the reproducibility of this procedure. Its important features include extended in vitro culture of fetal cells preceding nuclear transfer, as well as in vitro maturation and activation of oocytes and in vitro embryo culture. The cell culture and nuclear transfer techniques described here should allow the use of genetic modification procedures to produce tissues and organs from cloned pigs with reduced immunogenicity for use in xenotransplantation.

A spontaneous, autosomal, recessive mouse mutation exhibiting mild scaly skin, progressive scarring alopecia, slightly runted growth, and photophobia arose at The Jackson Laboratory in 1993 in the inbred mouse strain DBA/1LacJ. Because this mutant mouse showed genetic, anatomical, and laboratory similarities to the asebia mutation, crosses were done between the new mutant and mice carrying the asebia-J allele. Because the F1 offspring were affected, indicating the two mutants were allelic, the new mutation was named asebia-2J. Careful histological analysis of skin development of mice homozygous and heterozygous for either asebia-J or asebia-2J revealed that both types of mutant mice are very similar regardless of their background. Notable histopathological features of mice homozygous for either allele included extreme sebaceous gland hypoplasia, abnormally long anagen follicles, retained inner root sheath, hair fiber perforation of the anagen follicle base, and progressive follicular replacement by scarring. In this article we present a new pathogenetic hypothesis based on the importance of the sebaceous gland in hair fiber sheath dissociation: in the absence of a functional sebaceous gland the hair follicle is destroyed. The cutaneous pathology of this mutant mouse underscores the importance of the sebaceous gland to follicular biology and presents an animal model for studying the human scarring alopecias, which characteristically begin with sebaceous gland ablation.

Extensive investigation of vertebrate striated muscle titin has yielded significant insight into its structure and function in striated muscle. We have begun to investigate other members of the titin protein family found in vertebrate smooth muscle and nonmuscle cells. Smooth and nonmuscle titins resemble striated muscle titin in molecular size and morphology but differ in their interactions with myosin II filaments and in the structural contexts in which they exist in vivo. Divergence of these titins from the muscle titin paradigm demonstrates the versatility of this remarkable family of giant proteins.

We have refined the position of asebia locus by genotyping DNA from more than 600 backcross mice derived from asebia mouse and a genetically unrelated strain. One of the candidate genes in the locus is stearoyl-CoA desaturase (SCD). Previously two members of this gene family, namely SCD1 and SCD2, have been described. We have found, for the first time, that these SCD genes are expressed in skin. Moreover, we have identified a third species of SCD in the mouse skin. The most prominent SCD species is SCD1 in the mouse skin. The implications of this gene family to skin are discussed.

A method has been developed to determine the individual settings of the MLC leaves from the image of the beam portal. The portal image is analysed by a two-step approach: (i) The general orientation of the collimator leaves is determined. (ii) Next, a one-dimensional edge operator (generalized Laplacian) is applied in a scanline fashion to extract an array holding the image coordinates of the field edge. The prescribed position of each leaf is then compared with the position of the steepest gradient behind that leaf as determined from the portal image. To obtain adequate precision in the determination of the leaf positions, the dose rate dependency of the electronic image detector, the increased transmission through the leaf tips and flanges, and the properties of the edge detector used for image processing were investigated. From these studies, a set of correction terms were obtained that are used to correctly calculate the position of the field edge from the prescribed MLC leaf settings. If not corrected, a leaf position-dependent discrepancy in the range -0.5 to 1.0 mm will arise. The results from tests of this method, applying the correction terms, show that the leaf positions can be determined with a precision better than 0.1 mm (one standard deviation). The reproducibility of the leaf positions was found to be better than 0.1 mm.