Risks and Ultraviolet Budgets using Earth Observation (RUBEO): Including a nonstandard atmosphere and geographic ozone trend differences in risk assessments

No RIVM report number in publicationUV-budget maps (the geographical distribution of effective UV at ground level) can be derived from satellite data. These UV-budget maps visualise changes in effective UV caused by ozone depletion and changes in cloud cover and aerosol content. Alterations in UV-budget maps over time give - in combination with dose-effect models for UV-induced effects - insight in the associated risks for human health and the environment. This report describes the results of the RUBEO-project: calculating Risks and Ultraviolet Budgets using Earth Observation (RUBEO). RUBEO aims at a better cloud parameterisation and incorporating temporal and spatial resolution for surface albedo, aerosol content and tropospheric ozone content. The geographical distribution of ozone and UV climatology and trends over Europe are analysed, and a cost-benefit analysis of satellite based UV budget mapping is provided. The UV-budget mapping can be applied using TOMS and GOME ozone data. A large scale statistical analysis of cloud effects is given comparing ISCCP and TOMS based remote sensing methods with cloud effects derived from ground measurements. Both satellite derived methods correlate well (r 0.93) with the ground based analysis. Correction for non-zero albedo, under clear sky conditions, adds maximal 8% to the yearly effective UV-budget. Temporal and spatial differences in aerosol optical thickness and tropospheric ozone content, result in a decrease in effective UV of 3% for every 0.1 increase in aerosol optical thickness, and in a decrease in effective UV of 4% for every 10 DU increase in tropospheric ozone. Stratospheric ozone trends of -1 to -4% per decade observed over Europe correspond to a 0.5 to 4% increase in skin cancer weighted effective UV. The largest trends are seen in the central part of Western Europe. At present satellite based UV-budget maps form a functional basis for trend analysis and risk assessment. However, satellite data and ground-based observations are both indispensable. Maps for changing UV-budgets and associated skin cancer risks have been used in 'state of the environment', reports. Such overviews, regularly published by the Dutch National Institute of Public Health and the Environment (RIVM) and the European Environmental Agency (EPA), support the evaluation and formulation of adequate environmental policies. This report describes a project carried out in the framework of the Users Support Programme (USP-2), under responsibility of the Netherlands Remote Sensing Board (BCRS).Beleidscommissie Remote Sensing (BCRS

UV-radiation and health

Jaarlijks krijgen meer dan 51.000 mensen in Nederland te horen dat ze huidkanker hebben en overlijden ruim 900 mensen aan de gevolgen ervan. Sinds 1990 is het aantal gevallen verviervoudigd. Deze stijging is veel sterker dan bij andere vormen van kanker, en een verdere stijging dreigt (met een factor 2 tot 5). De gevaarlijkste vorm van huidkanker komt in Nederland relatief vaak voor, en binnen Europa behoort Nederland tot de koplopers. Blootstelling van de huid aan UV-straling is de voornaamste oorzaak van het ontstaan van huidkanker, en dan vooral door onverstandig zongedrag. De vergrijzing en de aantasting van de ozonlaag blijken slechts een deel van de toename aan huidkanker te verklaren. Het blootstellingsgedrag lijkt de hoofdrol te spelen en daarbij zijn het dragen van minder bedekkende kleding, meer vrije tijd en langere (zon/strand) vakanties van belang, maar ook klimaatverandering en het gebruik van kunstmatige UV-bronnen voor bruining dragen mogelijk bij. De belangrijkste manier om huidkanker te voorkomen is dan ook ervoor te zorgen dat de huid niet verbrandt door de zon of zonnebank. Maar ook zonder te verbranden kan de huid beschadigd raken. Daarom is het verstandig om de huiddelen die veelvuldig worden blootgesteld extra te beschermen en om daarbij rekening te houden met de zonkracht en de duur van het verblijf in de zon. Bij een hoogstaande (zomer)zon tussen 11 en 16 uur is meer bescherming nodig dan 's morgens vroeg en in de namiddag. Behalve aan huidkanker draagt UV-straling bij aan de vorming van staar en veroorzaakt het huidveroudering en sneeuwblindheid. Het is niet wenselijk om de zonblootstelling volledig te vermijden, omdat UV-blootstelling van de huid ook de voornaamste bron is van vitamine D. Deze vitamine is essentieel voor gezonde botten en spieren. Bovendien zijn er aanwijzingen dat vitamine D de kans op darmkanker kan verkleinen. Momenteel is er een felle wetenschappelijke discussie gaande welke hoeveelheid vitamine D de meeste gezondheidswinst oplevert. De kosten van de medische behandeling van huidkanker bedragen naar schatting circa 325 (250-400) miljoen euro per jaar. De kosten voor de behandeling van door UV veroorzaakte staar, worden geschat op 75-150 miljoen euro per jaar. De kosten zijn grotendeels vermijdbaar door verstandiger (zon)gedrag. De actuele zonkrachtmetingen (www.rivm.nl/zonkracht) en betere kennis over (ontwikkelingen in) blootstellingsgedrag en gezondheidseffecten dragen bij aan een goede voorlichting en preventie. Er is alle reden de kennisopbouw met betrekking tot UV-stralingsbescherming te versterken.Every year more than 51,000 new cases of skin cancer are diagnosed in the Netherlands and over 900 fatalities are reported. The number of new skin cancer cases is rising rapidly and since 1990 a fourfold increase has been observed. This increase is much stronger than for other types of cancer, and a further increase is expected (with a factor of 2-5). The incidence of melanoma of the skin in the Netherlands is among the highest in Europe. Exposure of the skin to UV-radiation is the primary cause of skin cancer, and sun-exposure is the primary source of UV-exposure. The increase in skin cancer incidence that has been observed is only partly explained by the ageing of the Dutch population and the depletion of the ozone layer. A change in exposure behaviour is probably the most dominant factor that could explain a major part of the increased skin cancer incidence. Changes in fashion, with more of the body exposed, shorter working hours and longer vacations, including an increase in summer holidays spent in southern Europe are likely causes. Climate change and the use of artificial tanning devices may also contribute. Skin cancer prevention should be focused on the avoidance of UV-induced erythema (sunburn) in solar and artificial exposures. Limiting the chronic exposure of the most exposed skin parts is also very important, because damage to the skin also occurs below the threshold of erythemal doses. It is, therefore, important to provide additional protection for the parts of the skin that are chronically exposed. Solar exposure is the most important UV-source and protection is most needed when the sun is high in the sky, in the summer months between 11:00 am and 16:00 (4 pm). The UV-index is a good indicator; it is much lower in the early morning or late afternoon/early evening. UV-exposure also contributes to the incidence of cataract and causes skin ageing and snow blindness (photokeratitis). Exposure of the skin to solar UV from the sun should not be completely avoided, however, as it is an important source of vitamin D. Vitamin D is essential for healthy bones and muscles, and there are indications that a high vitamin D status lowers the risk of developing colon cancer, and may also be a factor in the development of a number of other cancers and chronic diseases. At present, a scientific debate is ongoing regarding the minimally required and optimal levels of vitamin D, and how to best achieve them. In the Netherlands the estimated costs for medical treatments of skin cancer and precancerous skin lesions amount to 325 million Euro (250-400). Estimated medical costs for the UV-contribution to cataract formation are 75-150 million Euro per year. These costs can be substantially reduced if (solar) UV-exposure is restricted. Prevention is supported by Solar UV-index measurements (www.rivm.nl/zonkracht), and improved knowledge on UV-radiation exposure and associated health effects. Strengthening the knowledge building and dissemination of information about UV-radiation protection is vitally important.Ministerie van VW

High-dose carboplatin, thiotepa and cyclophosphamide (CTC) with peripheral blood stem cell support in the adjuvant therapy of high-risk breast cancer: a practical approach.

In 29 chemotherapy-naive patients with stage II-III breast cancer, peripheral blood stem cells (PBSCs) were mobilised following fluorouracil 500 mg m-2, epirubicin 90-120 mg m-2 and cyclophosphamide 500 mg m-2 (FEC) and granulocyte colony-stimulating factor (G-CSF; Filgrastim) 300 microgram s.c. daily. In all but one patient, mobilisation was successful, requiring three or fewer leucocytopheresis sessions in 26 patients; 28 patients subsequently underwent high-dose chemotherapy consisting of carboplatin 1600 mg m-2, thiotepa 480 mg m-2 and cyclophosphamide 6 g m-2 (CTC) followed by PBSC transplantation. Haemopoietic engraftment was rapid with a median time to neutrophils of 500 x 10(6) l(-1) of 9 days (range 8-10) in patients who received G-CSF after PBSC-transplantation; platelet transfusion independence was reached within a median of 10 days (range 7-16). Neutropenic fever occurred in 96% of patients. Gastrointestinal toxicity was substantial but reversible. Renal, neural or ototoxicity was not observed. Complications related to the central venous catheter were encountered in 64% of patients, with major vein thrombosis occurring in 18%. High-dose CTC-chemotherapy with PBSC-transplantation, harvested after mobilisation with FEC and G-CSF, is reasonably well tolerated without life-threatening toxicity and is a suitable high-dose strategy for the adjuvant treatment of breast cancer

Essential role of microfibrillar-associated protein 4 in human cutaneous homeostasis and in its photoprotection

UVB-induced cutaneous photodamage/photoaging is characterized by qualitative and quantitative deterioration in dermal extracellular matrix (ECM) components such as collagen and elastic fibers. Disappearance of microfibrillar-associated protein 4 (MFAP-4), a possible limiting factor for cutaneous elasticity, was documented in photoaged dermis, but its function is poorly understood. To characterize its possible contribution to photoprotection, MFAP-4 expression was either augmented or inhibited in a human skin xenograft photodamage murine model and human fibroblasts. Xenografted skin with enhanced MFAP-4 expression was protected from UVB-induced photodamage/photoaging accompanied by the prevention of ECM degradation and aggravated elasticity. Additionally, remarkably increased or decreased fibrillin-1-based microfibril development was observed when fibroblasts were treated with recombinant MFAP-4 or with MFAP-4-specific siRNA, respectively. Immunoprecipitation analysis confirmed direct interaction between MFAP-4 and fibrillin-1. Taken together, our findings reveal the essential role of MFAP-4 in photoprotection and offer new therapeutic opportunities to prevent skin-associated pathologies

Relationships between Hematopoiesis and Hepatogenesis in the Midtrimester Fetal Liver Characterized by Dynamic Transcriptomic and Proteomic Profiles

In fetal hematopoietic organs, the switch from hematopoiesis is hypothesized to be a critical time point for organogenesis, but it is not yet evidenced. The transient coexistence of hematopoiesis will be useful to understand the development of fetal liver (FL) around this time and its relationship to hematopoiesis. Here, the temporal and the comparative transcriptomic and proteomic profiles were observed during the critical time points corresponding to the initiation (E11.5), peak (E14.5), recession (E15.5), and disappearance (3 ddp) of mouse FL hematopoiesis. We found that E11.5-E14.5 corresponds to a FL hematopoietic expansion phase with distinct molecular features, including the expression of new transcription factors, many of which are novel KRAB (Kruppel-associated box)-containing zinc finger proteins. This time period is also characterized by extensive depression of some liver functions, especially catabolism/utilization, immune and defense, classical complement cascades, and intrinsic blood coagulation. Instead, the other liver functions increased, such as xenobiotic and sterol metabolism, synthesis of carbohydrate and glycan, the alternate and lectin complement cascades and extrinsic blood coagulation, and etc. Strikingly, all of the liver functions were significantly increased at E14.5-E15.5 and thereafter, and the depression of the key pathways attributes to build the hematopoietic microenvironment. These findings signal hematopoiesis emigration is the key to open the door of liver maturation

Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper

Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addresse

Inventory and classification of countermeasure zones in the case of a nuclear accident

Strengere richtlijnen voor maatregelen na kernongevallen hoeven vanwege veiligere kerncentrales niet te leiden tot veel grotere zones waarbinnen maatregelen moeten worden voorbereid. Dit blijkt uit onderzoek dat het RIVM heeft uitgevoerd in opdracht van het ministerie van VROM. Wanneer bij een kernongeval specifieke dosiswaarden (de interventieniveaus) worden overschreden, roept de overheid maatregelen af zoals schuilen, evacuatie en jodiumprofylaxe. Dit gebeurt om de blootstelling van de bevolking aan radioactiviteit te beperken. Op basis van deze interventieniveaus en een maatramp kunnen de zones worden bepaald waar maatregelen nodig zijn. Door de aanwezigheid van kerncentrales nabij de landsgrenzen zijn de gevolgen van kernongevallen meestal grensoverschrijdend. Mede daarom wil het ministerie van VROM de interventieniveaus aanpassen om betere overeenstemming te krijgen met de in Duitsland en Belgie gehanteerde niveaus. Daarnaast zijn er, gelet op inzichten uit recente veiligheidsstudies, redenen om de maatramp, die stamt uit de jaren zeventig, te herzien. Beide wijzigingen zijn meegenomen in de systematiek voor de bepaling van maatregelzones. Uit een analyse volgt dat de aanpassingen elkaar grotendeels compenseren waardoor de grootte van de gebieden niet veel hoeft te veranderen. De nieuw berekende maatregelzones zijn vervolgens in een classificatietabel verwerkt. Deze heeft twee functies: ten eerste kunnen overheden deze indeling gebruiken in rampenbestrijdingsplannen. Ten tweede kunnen hulpverlenende instanties bij kernongevallen op deze tabel teruggrijpen om snel de consequenties van het ongeval te kunnen communiceren.Stricter guidelines for intervention measures following a nuclear accident do not necessarily lead to much larger emergency planning zones. This is because safety standards of nuclear power plants have become more stringent as well. This is the conclusion drawn by the RIVM upon completion of a research project commissioned by the Ministry of Spatial Planning, Housing and the Environment of the Netherlands. If, in the aftermath of a nuclear accident, pre-determined radiation dose values - the so called intervention levels - are exceeded, the Dutch government will trigger intervention measures such as sheltering, evacuation and iodine prophylaxis to limit the exposure of the population to radioactivity. The extent of the zones where interventions are imposed can be determined on the basis of intervention levels and a representative emergency scenario. Because of the proximity of nuclear power plants to national borders, nuclear accidents tend to haveinternational consequences. A better correspondence between Dutch intervention levels and those of Germany and Belgium is one factor driving the wish of the Netherlands Ministry of Spatial Planning, Housing and the Environment to adjust Dutch intervention levels. In addition, recent safety studies suggest that the representative emergency scenario, which has been in use since the seventies to assess countermeasure zones, is outdated. Both of these factors have been considered in the calculation of countermeasure zones and found to largely compensate each other. This result implies that the extent of the zones can remain largely unchanged. Finally, a classification table has been constructed based on the newly calculated countermeasure zones. The classification serves two purposes. Firstly, local government authorities may use it in their emergency response plans. Secondly, in the case of a nuclear accident, emergency relief personnel can utilize this table to swiftly communicate the consequences of the accident.VRO