Thermal dosimetry for bladder hyperthermia treatment. An overview.

The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments

SAFEGUI: resampling-based tests of categorical significance in gene expression data made easy

Summary: A large number of websites and applications perform significance testing for gene categories/pathways in microarray data. Many of these packages fail to account for expression correlation between transcripts, with a resultant inflation in Type I error. Array permutation and other resampling-based approaches have been proposed as solutions to this problem. SAFEGUI provides a user-friendly graphical interface for the assessment of categorical significance in microarray studies, while properly accounting for the effects of correlations among genes. SAFEGUI incorporates both permutation and more recently proposed bootstrap algorithms that are demonstrated to be more powerful in detecting differential expression across categories of genes

Prevalence of actinic keratosis and skin cancer in a population of Dutch outdoor workers

Background: Outdoor work is associated with high and chronic exposure to solar ultraviolet radiation which might lead to an increased risk of developing skin (pre)malignancies. Prevalence of actinic keratosis (AK), basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC) and cutaneous melanoma (cM) in Dutch outdoor workers (OW) has not previously been investigated. Objective: This study compares the prevalence of premalignant lesions and skin tumours in OW and matched controls (non-OW). Methods: In a population-based cohort study, prevalence of premalignant lesions and skin tumours was investigated in a group of OW (n = 841) and controls matched 1:1 by age, sex, skin colour and tendency for sunburn. Skin examinations were conducted by physicians and skin cancer history was derived from the nationwide Dutch Pathology Registry. Information on OW was obtained through interviews. Conditional logistic regression models were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for associations between OW and BCC, cSCC, cM and (number of) AK. Results: AK was found in 22.7% of OW and 22.9% of non-OW, BCC in 14% of OW and 15.7% of non-OW, cSCC in 4.9% of OW and 3.4% of non-OW, and cM in 1.9% of OW and 2% of non-OW. There was no significant association between OW and premalignant lesions and skin tumours, with exception for developing ≥4 AKs (OR 1.3 [95% CI 1.0–1.78]). Conclusions: This study reveals high prevalence of premalignant lesions and skin tumours in a Dutch population. No association between OW and the occurrence of premalignant lesions and skin tumours was found, however, multiple AKs were more prevalent in OW.</p

Prevalence of actinic keratosis and skin cancer in a population of Dutch outdoor workers

Background: Outdoor work is associated with high and chronic exposure to solar ultraviolet radiation which might lead to an increased risk of developing skin (pre)malignancies. Prevalence of actinic keratosis (AK), basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC) and cutaneous melanoma (cM) in Dutch outdoor workers (OW) has not previously been investigated. Objective: This study compares the prevalence of premalignant lesions and skin tumours in OW and matched controls (non-OW). Methods: In a population-based cohort study, prevalence of premalignant lesions and skin tumours was investigated in a group of OW (n = 841) and controls matched 1:1 by age, sex, skin colour and tendency for sunburn. Skin examinations were conducted by physicians and skin cancer history was derived from the nationwide Dutch Pathology Registry. Information on OW was obtained through interviews. Conditional logistic regression models were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for associations between OW and BCC, cSCC, cM and (number of) AK. Results: AK was found in 22.7% of OW and 22.9% of non-OW, BCC in 14% of OW and 15.7% of non-OW, cSCC in 4.9% of OW and 3.4% of non-OW, and cM in 1.9% of OW and 2% of non-OW. There was no significant association between OW and premalignant lesions and skin tumours, with exception for developing ≥4 AKs (OR 1.3 [95% CI 1.0–1.78]). Conclusions: This study reveals high prevalence of premalignant lesions and skin tumours in a Dutch population. No association between OW and the occurrence of premalignant lesions and skin tumours was found, however, multiple AKs were more prevalent in OW.</p

Up and beyond: Building a mountain in the Netherlands

We discuss the idea of building a 2 km high mountain in the Netherlands. In this paper, we give suggestions on three important areas for the completion of this project. Issues like location, structure and sustainability are investigated and discussed in detail

Bias in protein and potassium intake collected with 24-h recalls (EPIC-Soft) is rather comparable across European populations

Purpose: We investigated whether group-level bias of a 24-h recall estimate of protein and potassium intake, as compared to biomarkers, varied across European centers and whether this was influenced by characteristics of individuals or centers. Methods: The combined data from EFCOVAL and EPIC studies included 14 centers from 9 countries (n = 1,841). Dietary data were collected using a computerized 24-h recall (EPIC-Soft). Nitrogen and potassium in 24-h urine collections were used as reference method. Multilevel linear regression analysis was performed, including individual-level (e.g., BMI) and center-level (e.g., food pattern index) variables. Results: For protein intake, no between-center variation in bias was observed in men while it was 5.7% in women. For potassium intake, the between-center variation in bias was 8.9% in men and null in women. BMI was an important factor influencing the biases across centers (p <0.01 in all analyses). In addition, mode of administration (p = 0.06 in women) and day of the week (p = 0.03 in men and p = 0.06 in women) may have influenced the bias in protein intake across centers. After inclusion of these individual variables, between-center variation in bias in protein intake disappeared for women, whereas for potassium, it increased slightly in men (to 9.5%). Center-level variables did not influence the results. Conclusion: The results suggest that group-level bias in protein and potassium (for women) collected with 24-h recalls does not vary across centers and to a certain extent varies for potassium in men. BMI and study design aspects, rather than center-level characteristics, affected the biases across center

Finite-size effects for anisotropic bootstrap percolation: logarithmic corrections

In this note we analyze an anisotropic, two-dimensional bootstrap percolation model introduced by Gravner and Griffeath. We present upper and lower bounds on the finite-size effects. We discuss the similarities with the semi-oriented model introduced by Duarte.Comment: Key words: Bootstrap percolation, anisotropy, finite-size effect

High Fat Diet-Induced Changes in Mouse Muscle Mitochondrial Phospholipids Do Not Impair Mitochondrial Respiration Despite Insulin Resistance

BACKGROUND: Type 2 diabetes mellitus and muscle insulin resistance have been associated with reduced capacity of skeletal muscle mitochondria, possibly as a result of increased intake of dietary fat. Here, we examined the hypothesis that a prolonged high-fat diet consumption (HFD) increases the saturation of muscle mitochondrial membrane phospholipids causing impaired mitochondrial oxidative capacity and possibly insulin resistance. METHODOLOGY: C57BL/6J mice were fed an 8-week or 20-week low fat diet (10 kcal%; LFD) or HFD (45 kcal%). Skeletal muscle mitochondria were isolated and fatty acid (FA) composition of skeletal muscle mitochondrial phospholipids was analyzed by thin-layer chromatography followed by GC. High-resolution respirometry was used to assess oxidation of pyruvate and fatty acids by mitochondria. Insulin sensitivity was estimated by HOMA-IR. PRINCIPAL FINDINGS: At 8 weeks, mono-unsaturated FA (16∶1n7, 18∶1n7 and 18∶1n9) were decreased (-4.0%, p<0.001), whereas saturated FA (16∶0) were increased (+3.2%, p<0.001) in phospholipids of HFD vs. LFD mitochondria. Interestingly, 20 weeks of HFD descreased mono-unsaturated FA while n-6 poly-unsaturated FA (18∶2n6, 20∶4n6, 22∶5n6) showed a pronounced increase (+4.0%, p<0.001). Despite increased saturation of muscle mitochondrial phospholipids after the 8-week HFD, mitochondrial oxidation of both pyruvate and fatty acids were similar between LFD and HFD mice. After 20 weeks of HFD, the increase in n-6 poly-unsaturated FA was accompanied by enhanced maximal capacity of the electron transport chain (+49%, p = 0.002) and a tendency for increased ADP-stimulated respiration, but only when fuelled by a lipid-derived substrate. Insulin sensitivity in HFD mice was reduced at both 8 and 20 weeks. CONCLUSIONS/INTERPRETATION: Our findings do not support the concept that prolonged HF feeding leads to increased saturation of skeletal muscle mitochondrial phospholipids resulting in a decrease in mitochondrial fat oxidative capacity and (muscle) insulin resistance

Up and Beyond - Building a Mountain in the Netherlands

We discuss the idea of building a 2 km high mountain in the Netherlands. In this paper, we give suggestions on three important areas for the completion of this project. Issues like location, structure and sustainability are investigated and discussed in detail