The Contribution of Renewable Energy to a Sustainable Energy System

This report provides an overview of the main results from the scenarios analysed in the CASCADE MINTS project to assess the role of renewables in solving global and European en-ergy and environmental issues. The main conclusion is that renewable energy can make a sub-stantial contribution to reducing greenhouse gas emissions and improving diversification of the European energy production portfolio, although other technologies will also be needed in order to achieve post Kyoto targets. The report outlines the impacts, costs and benefits of ambitious renewables targets for Europe in the medium term. It also presents lessons learned from taking the global perspective

Analysis of MHC class I and II expression in relation to presence of HPV genotypes in premalignant and malignant cervical lesions.

Cervical intraepithelial neoplasia (CIN) grades I to III lesions (n = 94) and squamous cell carcinomas of the uterine cervix (n = 27) were analysed for MHC class I and II expression and presence of HPV genotypes. MHC class I and II expression was studied by immunohistochemistry and HPV typing was performed by general primer- and type-specific primer mediated PCR (GP/TS PCR). Both techniques were performed on paraffin embedded tissue sections. Results show disturbed MHC class I heavy chain expression in CIN I to CIN III, as well as in cervical carcinomas. Upregulated MHC class II expression on dysplastic epithelial cells was also found in the different CIN groups and carcinomas. Prevalence of HPV genotypes increased with the severity of the lesion, mainly due to the contribution of the HPV types 16 and 18. No correlation could be established between the presence of specific HPV genotypes and any MHC expression pattern in the different CIN groups or cervical carcinomas. In some cases these data were confirmed by RNA in situ hybridisation showing HPV 16 E7 transcripts in the same dysplastic/neoplastic cells from which MHC status was determined. The results indicate that local differences may exist in the type of cellular immune response to HPV induced lesions

Screen-detected breast cancers have a lower mitotic activity index

We know that screening for breast cancer leads to detection of smaller tumours with less lymph node metastases. Could it be possible that the decrease in mortality after screening is not only caused by this earlier stage, but also by a different mitotic activity index (MAI) of the tumours that are detected by screening? Is MAI a prognostic factor for recurrence-free survival? A retrospective study was carried out of 387 patients with breast cancer, treated at the University Hospital Nijmegen between January 1992 and September 1997. Ninety patients had screen-detected breast cancer, 297 patients had breast cancers detected outside the screening programme. The MAI, other prognostic factors and recurrence-free survival were determined. In non-screen-detected tumours the MAI is twice as high as in screen-detected tumours, even after correction for age took place. The MAI correlated well with other tumour characteristics. The MAI in itself is a prognostic factor for recurrence-free survival. Favourable outcome in screen detected breast cancer is not entirely caused by detecting cancer in early stages: quantitative features such as the MAI indicate a less malignant character of screen detected breast cancer. The MAI is an independent prognostic factor for recurrence-free survival. © 2000 Cancer Research Campaig

Number of apoptotic cells as a prognostic marker in invasive breast cancer

Apoptosis plays an important role in tumorigenesis. Tumour growth is determined by the rate of cell proliferation and cell death. We counted the number of apoptotic cells in haematoxylin and eosin (H&E)-stained tumour sections in series of 172 grade I and II invasive breast cancers with long-term follow-up. The number of apoptotic cells in ten high-power fields were converted to the number of apoptotic cells per mm2to obtain the apoptotic index (AI). The AI showed a positive correlation to the mitotic activity index (MAI) (P = 0.0001), histological grade (P< 0.0001) and worse tumour differentiation. Patients with high AI showed shorter overall survival than patients with low AI in the total group as well as in the lymph node-positive group. Tumour size, MAI, lymph node status and AI were independent prognostic indicators in multivariate analysis. The AI was shown to be of additional prognostic value to the MAI in the total patients group as well as in the lymph node-positive group. The correlation between the AI and the MAI points to linked mechanisms of apoptosis and proliferation. Since apoptotic cells can be counted with good reproducibility in H&E-stained tumour sections, the AI may be used as an additional prognostic indicator in invasive breast cancer. © 2000 Cancer Research Campaig

Human papillomavirus infection in Rwanda at the moment of implementation of a national HPV vaccination programme

Background: Cervical cancer is the most common female cancer in Rwanda that, in 2011, became the first African country to implement a national vaccination programme against human papillomavirus (HPV). Methods: To provide a robust baseline for future evaluations of vaccine effectiveness, cervical cell specimens were obtained from 2508 women aged 18–69 years from the general population in Kigali, Rwanda, during 2013/14. 20 % of women were HIV-positive. Samples were used for liquid-based cytology and HPV testing (44 types) with GP5+/6+ PCR. Results: HPV prevalence was 34 %, being highest (54 %) in women ≤19 years and decreasing to 20 % at age ≥50. Prevalence of high risk (HR) HPV and cytological abnormalities was 22 and 11 % respectively (including 2 % with high-grade squamous intraepithelial lesions, HSIL) decreasing with age. Age-standardised prevalence of HR HPV was 22 % (or 19 % among HIV-negative women), and HPV16 was the most common type. Prevalence of HPV and cytological abnormalities were significantly higher in HIV-positive than HIV-negative women, and the difference increased with age. Other significant risk factors for HPV positivity in multivariate analyses were high lifetime number of sexual partners, receiving cash for sex, and being a farmer. 40 % of women with HSIL were infected with HPV16/18 and there was no significant difference between HIV-positive and HIV-negative women. Conclusions: This study confirms Rwanda to be a setting of high prevalence of HPV and cervical disease that is worsened by HIV. These data will serve as a robust baseline for future evaluations of HPV vaccine programme effectiveness

De energietransitie: een nieuwe dimensie in ons landschap

De transitie naar een duurzame energievoorziening heeft op veel terreinen ingrijpende gevolgen voor onze samenleving. Het gaat onder meer om een verandering van leefomgeving en landschap. Voor een succesvolle energietransitie is het nodig om nu al rekening te houden met de ruimtelijke vormgeving van nieuwe energielandschappen en de manier waarop die tot stand komen. Dit betekent dat alle betrokkenen samen energielandschappen ontwerpen waarin mens en technologie elkaar op een nieuwe manier ontmoeten. Een andere manier van denken: niet het ruimtelijk inpassen, maar het creëren van landschappen die door mensen worden gewaardeerd en economisch haalbaar zijn. Landschappen die zorgen dat de overgang naar een duurzame, koolstofarme toekomst breed gedragen wordt en snel kan plaatsvinden. ECN en WUR hebben hun kennis over energietechnologie en landschapsarchitectuur gebundeld in dit paper. Zo willen ze een bijdrage leveren aan de discussie over wat wenselijk en noodzakelijk is om de energietransitie ruimtelijk in goede banen te leiden

Screen-detected vs clinical breast cancer: the advantage in the relative risk of lymph node metastases decreases with increasing tumour size

Screen-detected (SD) breast cancers are smaller and biologically more indolent than clinically presenting cancers. An often debated question is: if left undiagnosed during their preclinical phase, would they become more aggressive or would they only increase in size? This study considered a registry-based series (1988–1999) of 3329 unifocal, pT1a-pT3 breast cancer cases aged 50–70 years, of which 994 were SD cases and 2335 clinical cases. The rationale was that (1) the average risk of lymph node involvement (N+) is lower for SD cases, (2) nodal status is the product of biological aggressiveness and chronological age of the disease, (3) for any breast cancer, tumour size is an indicator of chronological age, and (4) for SD cases, tumour size is specifically an indicator of the duration of the preclinical phase, that is, an inverse indicator of lead time. The hypothesis was that the relative protection of SD cases from the risk of N+ and, thus, their relative biological indolence decrease with increasing tumour size. The odds ratio (OR) estimate of the risk of N+ was obtained from a multiple logistic regression model that included terms for detection modality, tumour size category, patient age, histological type, and number of lymph nodes recovered. A term for the detection modality-by-tumour size category interaction was entered, and the OR for the main effect of detection by screening vs clinical diagnosis was calculated. This increased linearly from 0.05 (95% confidence interval: 0.01–0.39) in the 2–7 mm size category to 0.95 (0.64–1.40) in the 18–22 mm category. This trend is compatible with the view that biological aggressiveness of breast cancer increases during the preclinical phase

⁸⁹Zr-pembrolizumab imaging as a non-invasive approach to assess clinical response to PD-1 blockade in cancer

Background: Programmed cell death protein 1 (PD-1) antibody treatment is standard of care for melanoma and non-small-cell lung cancer (NSCLC). Accurately predicting which patients will benefit is currently not possible. Tumor uptake and biodistribution of the PD-1 antibody might play a role. Therefore, we carried out a positron emission tomography (PET) imaging study with zirconium-89 ( 89Zr)-labeled pembrolizumab before PD-1 antibody treatment. Patients and methods: Patients with advanced or metastatic melanoma or NSCLC received 37 MBq (1 mCi) 89Zr-pembrolizumab (∼2.5 mg antibody) intravenously plus 2.5 or 7.5 mg unlabeled pembrolizumab. After that, up to three PET scans were carried out on days 2, 4, and 7. Next, PD-1 antibody treatment was initiated. 89Zr-pembrolizumab tumor uptake was calculated as maximum standardized uptake value (SUV max) and expressed as geometric mean. Normal organ uptake was calculated as SUV mean and expressed as a mean. Tumor response was assessed according to (i)RECIST v1.1. Results: Eighteen patients, 11 with melanoma and 7 with NSCLC, were included. The optimal dose was 5 mg pembrolizumab, and the optimal time point for PET scanning was day 7. The tumor SUV max did not differ between melanoma and NSCLC (4.9 and 6.5, P = 0.49). Tumor 89Zr-pembrolizumab uptake correlated with tumor response (P trend = 0.014) and progression-free (P = 0.0025) and overall survival (P = 0.026). 89Zr-pembrolizumab uptake at 5 mg was highest in the spleen with a mean SUV mean of 5.8 (standard deviation ±1.8). There was also 89Zr-pembrolizumab uptake in Waldeyer's ring, in normal lymph nodes, and at sites of inflammation. Conclusion: 89Zr-pembrolizumab uptake in tumor lesions correlated with treatment response and patient survival. 89Zr-pembrolizumab also showed uptake in lymphoid tissues and at sites of inflammation