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BACKGROUND Cerebral dural arteriovenous fistulas (dAVFs) presenting with hemorrhage are so rare that reports on their characteristics and guidelines for their acute management are scarce. OBJECTIVE To identify characteristics of the clinical and radiological presentation of hemorrhaging dAVFs, and establish their frequency of early rebleed so that implications for their acute management can be drawn. METHODS Retrospective analysis of all patients admitted with intracranial hemorrhage from a dAVF during the years 2011 to 2018. RESULTS Twenty patients (14 males) with a median age of 61 yr (27-75 yr) were included. Thunderclap headache was the presenting symptom in 13 (65%) patients. Rebleed prior to treatment occurred in 35% of the patients at median 7.5 h (range 3-96 h) after the ictus. All dAVFs had retrograde venous drainage and a venous aneurysm with a bleb was the source of hemorrhage in 16 (80%) patients, all of them presenting with headache. In contrast, patients bleeding due to diffuse venous hypertension presented with neurological deficits. Endovascular treatment was successful in 2 cases; hence, definite dAVF treatment was surgical in 18 (90%) patients. At median 7 mo (2-29 mo) after the ictus, 13 (65%) patients were in Glasgow Outcome Scale-Extended 7 or 8. CONCLUSION The typical presentation of hemorrhage from a cranial dAVF is thunderclap headache. The origin of hemorrhage is often a ruptured venous aneurysm with a bleb. The high frequency of early rebleeds warrants management strategies equivalent to those established for aneurysmal subarachnoid hemorrhage. Overall outcome is favorable.

RNA interference (RNAi) is being developed and exploited to improve plants by modifying endogenous gene expression as well as to target pest and pathogen genes both within plants (i.e. host-induced gene silencing) and/or as topical applications (e.g. spray-induced gene silencing). RNAi is a natural mechanism which can be exploited to make a major contribution towards integrated pest management and sustainable agricultural strategies needed worldwide to secure current and future food production. RNAi plants are being assessed and regulated using existing regulatory frameworks for GMO. However, there is an urgent need to develop appropriate science-based risk assessment procedures for topical RNAi applications within existing plant protection products legislation.

Net cerebrospinal fluid (CSF) flow within the cerebral aqueduct is usually considered to be antegrade, i.e., from the third to the fourth ventricle with volumes ranging between 500 and 600 ml over 24 h. Knowledge of individual CSF flow dynamics, however, is hitherto scarcely investigated. In order to explore individual CSF flow rate and direction, we assessed net aqueductal CSF flow in individuals with intracranial aneurysms with or without a previous subarachnoid hemorrhage (SAH). A prospective observational study was performed utilizing phase-contrast magnetic resonance imaging (PC-MRI) to determine the magnitude and direction of aqueductal CSF flow with an in-depth, pixel-by-pixel approach. Estimation of net flow was used to calculate CSF flow volumes over 24 h. PC-MRI provides positive values when flow is retrograde. The study included eight patients with intracranial aneurysms. Four were examined within days after their SAH; three were studied in the chronic stage after SAH while one patient had an unruptured intracranial aneurysm. There was a vast variation in magnitude and direction of aqueductal CSF flow between individuals. Net aqueductal CSF flow was retrograde, i.e., directed towards the third ventricle in 5/8 individuals. For the entire patient cohort, the estimated net aqueductal CSF volumetric flow rate (independent of direction) was median 898 ml/24 h (ranges 69 ml/24 h to 12.9 l/24 h). One of the two individuals who had a very high estimated net aqueductal CSF volumetric flow rate, 8.7 l/24 h retrograde, later needed a permanent CSF shunt. The magnitude and direction of net aqueductal CSF flow vary extensively in patients with intracranial aneurysms. Following SAH, PC-MRI may offer the possibility to perform individualized assessments of the CSF circulation.

The environmental risk assessment of the insect resistant genetically modified maize MON 89034 (Reference EFSA/GMO/BE/2011/90) has been performed by the Panel on Genetically Modified Organisms (GMO) of the Norwegian Scientific Committee for Food Safety (VKM). VKM has been requested by the Norwegian Directorate for Nature Management and the Norwegian Food Safety Authority to issue a preliminary scientific opinion on the safety of the genetically modified maize MON 89034 (Unique identifier MON-89Ø34-3) for cultivation, and submit relevant scientific comments or questions to EFSA on the application EFSA/GMOBE/2011/90. The current submission is intended to complement application EFSA-GMO-NL-2007-37, which was approved by Commission Decision 2009/813/EC of 30 October 2009, authorising the placing on the market of products containing, consisting of, or produced from genetically modified maize MON 89034 (scope import, processing, food and feed). Maize MON89034 has previously been assessed by the VKM GMO Panel in connection with EFSA´s public hearing of the application EFSA/GMO/NL/2007/37 (VKM 2008a). Preliminary health- and environmental risk assessments of several stacked events, with MON 89034 as one of the parental lines, have also been performed by the VKM GMO Panel (VKM 2009a, b, c; VKM 2010a,b). The environmental risk assessment of the maize MON 89034 is based on information provided by the applicant in the application EFSA/GMO/BE/2011/90, and scientific comments from EFSA and other member states made available on the EFSA website GMO Extranet. The risk assessment also considered peer-reviewed scientific literature as relevant. The VKM GMO Panel has evaluated MON 89034 with reference to its intended uses in the European Economic Area (EEA), and according to the principles described in the Norwegian Food Act, the Norwegian Gene Technology Act and regulations relating to impact assessment pursuant to the Gene Technology Act, Directive 2001/18/EC on the deliberate release into the environment of genetically modified organisms, and Regulation (EC) No 1829/2003 on genetically modified food and feed. The Norwegian Scientific Committee for Food Safety has also decided to take account of the appropriate principles described in the EFSA guidelines for the risk assessment of GM plants and derived food and feed (EFSA 2006, 2011a), the environmental risk assessment of GM plants (EFSA 2010), the selection of comparators for the risk assessment of GM plants (EFSA 2011b), and for the post-market environmental monitoring of GM plants (EFSA 2006, 2011c). The scientific risk assessment of maize MON 89034 include molecular characterisation of the inserted DNA and expression of target proteins, comparative assessment of agronomic and phenotypic characteristics, unintended effects on plant fitness, potential for gene transfer, interactions between the GM plant and target and non-target organisms, effects on biogeochemical processes and evaluations of the post-market environmental plan. In line with its mandate, VKM emphasised that assessments of sustainable development, societal utility and ethical considerations, according to the Norwegian Gene Technology Act and Regulations relating to impact assessment pursuant to the Gene Technology Act, shall not be carried out by the Panel on Genetically Modified Organisms. The genetically modified maize MON 89034 was developed to provide protection against certain lepidopteran target pest, including European corn borer (Ostrinia nubilalis) and Mediterranean corn borer (Sesamia nonagrioides). Protection is achieved through expression in the plant of two insecticidal Cry proteins, Cry1A.105 and Cry2Ab2, derived from Bacillus thuringiensis, a common soil bacterium. Cry1A.105, encoded by the cry1A.105 gene, is a chimeric protein made up of different functional domains derived from three wild-type Cry proteins from B. thuringiensis subspecies kurstaki and aizawai. The Cry2Ab2 protein is encoded by the cry2Ab2 gene derived from B. thuringiensis subspecies kurstaki. Molecular characterization: Appropriate analysis of the integration site, including flanking sequence and bioinformatics analysis, has been performed to characterise the transformation event MON 89034. The results of the segregation analysis are consistent with a single site of insertion for the cry1A.105 and cry2Ab2 gene expression cassettes and confirm the results of the molecular characterisation. Molecular analysis of both self-pollinated and cross-fertilised lines, representing a total of seven different generations, indicates that the inserted DNA is stably transformed and inherited from one generation to the next. No genes that encode resistance to antibiotics are present in the genome of MON 89034 maize. The molecular characterisation confirmed the absence of both the aad and nptII genes, which were used in the cloning and transformation process. Event MON 89034 and the physical, chemical and functional characteristics of the proteins have previously been evaluated by The VKM Panel on Genetically Modified Organisms, and considered satisfactory (VKM 2008a). Comparative assessment: The field trials for comparative assessment of agronomic and phenotypic characteristics of maize MON 89034 in the USA (2004-2005) and Europe (2007), have been performed in accordance with the EFSAs guidelines for risk assessment of genetically modified plants and derived food and feed (EFSA 2010, 2011a). Based on results from the comparative analyses, it is concluded that maize MON 89034 is agronomically and phenotypically equivalent to the conventional counterpart and commercial available reference varieties, with the exception of the lepidopteran-protection trait. The field evaluations support a conclusion of no phenotypic changes indicative of increased plant weed/pest potential of MON 89034 compared to conventional maize. Evaluations of ecological interactions between maize MON 89034 and the biotic and abiotic environment indicate no unintended effects of the introduced trait on agronomic and phenotypic characteristics. Environmental risk: There are no reports of the target Lepidopteran species attaining pest status on maize in Norway. Since there are no Bt-based insecticides approved for use in Norway, and lepidopteran pests have not been registered in maize, issues related to resistance evolution in target pests are not relevant at present for Norwegian agriculture. Published scientific studies show no or negligible adverse effects of Cry1A.105 and Cry2Ab2 proteins on non-target arthropods that live on or in the vicinity of maize plants. Cultivation of maize MON 89034 is not considered to represent a threat to the prevalence of red-listed species in Norway. Few studies have been published examining potential effects of Cry1A.105 and Cry2Ab toxin on ecosystems in soil, mineralization, nutrient turnover and soil communities. Some field studies have indicated that root exudates and decaying plant material containing Cry proteins may affect population size and activity of rhizosphere organisms (soil protozoa and microorganisms). However, data are only available from short term experiments and predictions of potential long term effects are difficult to deduce. Most studies conclude that effects on soil microorganisms and microbial communities are transient and minor compared to effects caused by agronomic and environmental factors. Few studies have assessed the impact of Cry proteins on non-target aquatic arthropods and the fate of these proteins in senescent and decaying maize detritus in aquatic environments. Further studies with better experimental design are needed for the assessment of the potential effects of Bt crops on aquatic organisms. However, exposure of non-target organisms to Cry proteins in aquatic ecosystems is likely to be very low, and potential exposure of Bt toxins to non-target organisms in stream ecosystems in Norway is considered to be negligible. Maize is the only representative of the genus Zea in Europe, and there are no cross-compatible wild or weedy relatives outside cultivation with which maize can hybridise and form backcross progeny. Vertical gene transfer in maize therefore depends on cross-pollination with other conventional or organic maize varieties. In addition, unintended admixture of genetically modified material in seeds represents a possible way for gene flow between different crop cultivations. The risk of pollen flow from maize volunteers is negligible under Norwegian growing conditions. In addition to the data presented by the applicant, the VKM GMO Panel is not aware of any scientific report of increased establishment and spread of maize MON 89034 and any change in survival (including over-wintering), persistence and invasiveness capacity. Because the general characteristics of maize MON 89034 are unchanged, insect resistance are not likely to provide a selective advantage outside cultivation in Norway. Since MON 89034 has no altered agronomic and phenotypic characteristics, except for the specific target pest resistance, the VKM GMO Panel is of the opinion that the likelihood of unintended environmental effects due to the establishment and survival of maize MON 89034 will be no different to that of conventional maize varieties in Norway The environmental risk assessment will be completed and finalized by the VKM Panel on Genetically Modified Organisms when requested additional information from the applicant is available.

In preparation for a legal implementation of EU-regulation 1829/2003, the Norwegian Scientific Committee for Food Safety (VKM) has been requested by the Norwegian Directorate for Nature Management to conduct final environmental risk assessments for all genetically modified organisms (GMOs) and products containing or consisting of GMOs that are authorized in the European Union under Directive 2001/18/EC or Regulation 1829/2003/EC. The assignment includes a scientific environmental risk assessment of oilseed rape T45 (Reference EFSA/GMO/UK/2005/25) from Bayer CropScience for food and feed uses, import and processing. Oilseed rape T45 has previously been risk assessed by the VKM Panel on Genetically Modified Organisms (GMO), commissioned by the Norwegian Food Safety Authority related to the EFSAs public hearing in 2007 (VKM 2007a). Food additives produced from T45 oilseed rape were notified in the EU as existing food additives within the meaning of Article 8 (1)(b) of Regulation 1829/2003, authorized under Directive 89/10/EEC (Community Register 2005). Feed materials produced from T45 were also notified as existing feed products containing, consisting of or produced from T45 according to Articles 8 and 20 of Regulation (EC) No 1829/2003 in 2003. A notification for placing on the market of T45 according to the Directive 2001/18/EC was submitted in March 2004 (C/GB/04/M5/4), covering import and processing of T45 into food and feed. The application was further transferred into Regulation (EC) No 1829/2003 in November 2005 (EFSA/GMO/UK/2005/25). An application for renewal of authorisation for continued marketing of food additives and feed materials produced from T45 oilseed rape was submitted under Regulation (EC) No 1829/2003 in 2007 (EFSA/GMO/RX/T45). The EFSA GMO Panel performed one single comprehensive risk assessment for all intended uses of genetically modified oilseed rape T45, and issued a comprehensive scientific opinion for both applications submitted under Regulation (EC) No 1829/2003. The scientific opinion was published in January 30 2008 (EFSA 2008), and food and feed products containing or produced from oilseed rape T45 was approved by Commission Decision 26 March 2009 (Commission Decision 2009/184/EC). The oilseed rape T45 is however currently being phased out (EU-COM 2009). The commercialisation of T45 oilseed rape seeds in third countries was stopped after the 2005 planting season and stocks of all oilseed rape T45 lines have been recalled from distribution and destroyed. The applicant commits not to commercialize the event in the future and the import will therefore be restricted to adventitious levels in oilseed rape commodity. Thus the incidence of oilseed rape T45 in the EU is expected to be limited. The environmental risk assessment of the oilseed rape T45 is based on information provided by the notifier in the application EFSA/GMO/UK/2005/25 and EFSA/GMO/RX/T45, and scientific comments from EFSA and other member states made available on the EFSA website GMO Extranet. The risk assessment also considered other peer-reviewed scientific literature as relevant. The VKM GMO Panel has evaluated T45 with reference to its intended uses in the European Economic Area (EEA), and according to the principles described in the Norwegian Food Act, the Norwegian Gene Technology Act and regulations relating to impact assessment pursuant to the Gene Technology Act, Directive 2001/18/EC on the deliberate release into the environment of genetically modified organisms, and Regulation (EC) No 1829/2003 on genetically modified food and feed. The Norwegian Scientific Committee for Food Safety has also decided to take account of the appropriate principles described in the EFSA guidelines for the risk assessment of GM plants and derived food and feed (EFSA 2006, 2011a), the environmental risk assessment of GM plants (EFSA 2010), the selection of comparators for the risk assessment of GM plants (EFSA 2011b), and for the post-market environmental monitoring of GM plants (EFSA 2006, 2011c). The scientific risk assessment of oilseed rape T45 include molecular characterisation of the inserted DNA and expression of target proteins, comparative assessment of agronomic and phenotypic characteristics, unintended effects on plant fitness, potential for horizontal and vertical gene transfer, and evaluations of the post-market environmental plan. In line with its mandate, VKM emphasised that assessments of sustainable development, societal utility and ethical considerations, according to the Norwegian Gene Technology Act and Regulations relating to impact assessment pursuant to the Gene Technology Act, shall not be carried out by the Panel on Genetically Modified Organisms. The glufosinate ammonium-tolerant oilseed rape transformation event T45 (Unique Identfier ACSBNØØ8-2) was developed by Agrobacterium-mediated transformation of protoplast from the conventional oilseed rape cultivar “AC Excel”. T45 contains a synthetic version of the native pat gene isolated from the bacteria Streptomyces viridochromogenes, strain Tü 494. The inserted gene encodes the enzyme phosphinothricin acetyltransferase (PAT), which confers tolerance to the herbical active substance glufosinate ammonium. The PAT enzyme detoxifies glufosinate-ammonium by acetylation of the L-isomer into N-acetyl-L-glufosinate ammonium (NAG) which does not inhibit glutamine synthetase and therefore confers tolerance to the herbicide. Glufosinate ammonium-tolerant oilseed rape transformation event T45 has been conventionally bred into an array of spring-type oilseed rape varieties. Molecular characterization: The molecular characterisation data established that only one copy of the gene cassette is integrated in the oilseed rape genomic DNA. Appropriate analysis of the integration site including sequence determination of the inserted DNA and flanking regions and bioinformatics analysis have been performed. Bioinformatics analyses of junction regions demonstrated the absence of any potential new ORFs coding for known toxins or allergens. The genetic stability of transformation event T45 was demonstrated at the genomic level over multiple generations by Southern analysis. Segregation analysis shows that event T45 is inherited as dominant, single locus trait. Phenotypic stability has been confirmed by stable tolerance to the herbicide for T45 lines and varieties derived from the event grown in Canada since 1993. Oilseed rape transformation event T45 and the physical, chemical and functional characteristics of the proteins have previously been evaluated by The VKM Panel on Genetically Modified Organisms, and considered satisfactory (VKM 2007a). Comparative assessment: Based on results from comparative analyses of data from field trials located at representative sites and environments in Canada in 1995-1997, it is concluded that oilseed rape T45 is agronomically and phenotypically equivalent to the conventional counterpart and commercial available reference varieties, with the exception of maturity and the herbicide tolerance conferred by the PAT protein. The field evaluations support a conclusion of no phenotypic changes indicative of increased plant weed/pest potential of event T45 compared to conventional oilseed rape. Furthermore, the results demonstrate that in-crop applications of glufosinate herbicide do not alter the phenotypic and agronomic characteristics of event T45 compared to conventional oilseed rape. Environmental risk: According to the applicant, the event T45 has been phased out, and stocks of all oilseed rape T45 lines have been recalled from distribution and destroyed since 2005. However, since future cultivation and import of oilseed rape T45 into the EU/EEA area cannot be entirely ruled out, the environmental risk assessment consider exposure of viable seeds of T45 through accidental spillage into the environment during transportation, storage, handling, processing and use of derived products. Oilseed rape is mainly a self-pollinating species, but has entomophilous flowers capable of both self- and cross-pollinating. Normally the level of outcrossing is about 30%, but outcrossing frequencies up to 55% are reported. Several plant species related to oilseed rape that are either cultivated, occurs as weeds of cultivated and disturbed lands, or grow outside cultivation areas to which gene introgression from oilseed rape could be of concern. These are found both in the Brassica species complex and in related genera. A series of controlled crosses between oilseed rape and related taxa have been reported in the scientific literature. Because of a mismatch in the chromosome numbers most hybrids have a severely reduced fertility. Exceptions are hybrids obtained from crosses between oilseed rape and wild turnip (B. rapa ssp. campestris) and to a lesser extent, mustard greens (B. juncea), where spontaneously hybridising and transgene introgression under field conditions have been confirmed. Wild turnip is native to Norway and a common weed in arable lowlands. There is no evidence that the herbicide tolerant trait results in enhanced fitness, persistence or invasiveness of oilseed rape T45, or hybridizing wild relatives, compared to conventional oilseed rape varieties, unless the plants are exposed to herbicides with the active substance glufosinate ammonium. Glufosinate ammonium-containing herbicides have been withdrawn from the Norwegian market since 2008, and the substance will be phased out in the EU in 2017 for reasons of reproductive toxicity. Accidental spillage and loss of viable seeds of T45 during transport, storage, handling in the environment and processing into derived products is, however, likely to take place over time, and the establishment of small populations of oilseed rape T45 cannot be excluded. Feral oilseed rape T45 arising from spilled seed could theoretically pollinate conventional crop plants if the escaped populations are immediately adjacent to field crops, and shed seeds from cross-pollinated crop plants could emerge as GM volunteers in subsequent crops. However, both the occurrence of feral oilseed rape resulting from seed import spills and the introgression of genetic material from feral oilseed rape populations to wild populations are likely to be low in an import scenario. Apart from the glufosinate tolerance trait, the resulting progeny will not possess a higher fitness and will not be different from progeny arising from cross-fertilisation with conventional oilseed rape varieties. The occurrence of feral oilseed rape resulting from seed import spills and the introgression of genetic material from feral oilseed rape populations to wild populations are likely to be low in an import scenario in Norway. Overall conclusion: Taking into account the expected limited import of oilseed rape T45 (EU COM 2009), the VKM GMO Panel considers that the routes of gene flow from T45 would not introduce significant numbers of transgenic plants into agricultural areas or result in any environmental consequences in Norway. The VKM GMO Panel concludes that oilseed rape T45 is unlikely to have any adverse effect on the environment in Norway in the context of its intended usage.

In preparation for a legal implementation of EU-regulation 1829/2003, the Norwegian Scientific Committee for Food Safety (VKM) has been requested by the Norwegian Directorate for Nature Management to conduct final environmental risk assessments for all genetically modified organisms (GMOs) and products containing or consisting of GMOs that are authorized in the European Union under Directive 2001/18/EC or Regulation 1829/2003/EC. The request covers scope(s) relevant to the Gene Technology Act. The request does not cover GMOs that VKM already has conducted its final risk assessments on. However, the Directorate requests VKM to consider whether updates or other changes to earlier submitted assessments are necessary. MON810 notification C/F/95/12-02 is approved under Directive 90/220/EEC for cultivation, seed production, import and processing into feeding stuffs and industrial purposes since 22 April 1998 (Commission Decision 98/294/EC). In December 1997, food and food ingredients derived from the progeny of maize line MON810 were notified under Article 5 of Regulation (EC) No 258/97 on novel foods and novel food ingredients. In addition, existing food and feed products containing, consisting of or produced from MON810 were notified according to Articles 8 and 20 of Regulation (EC) No 1829/2003 and were placed in the Community Register in 2005. Three applications for renewal of the authorisation for continued marketing of (1) existing food and food ingredients produced from MON810; (2) feed consisting of and/or containing maize MON810, and MON810 for feed use (including cultivation); and (3) food and feed additives, and feed materials produced from maize MON810 within the framework of Regulation (EC) No 1829/2003 were submitted in 2007. Maize MON810 has previously been assessed by the VKM GMO Panel commissioned by the Norwegian Directorate for Nature Management in connection with the national finalisation of the procedure of the notification C/F/95/12/02 (VKM 2007a,b). In addition, MON810 has been evaluated by the VKM GMO Panel as a component of several stacked GM maize events (VKM 2005a,b,c, VKM 2007c, VKM 2008, VKM 2009, VKM 2012). Due to the publication of updated guidelines for environmental risk assessments of genetically modified plants and new scientific literature, the VKM GMO Panel has decided to deliver an updated environmental risk assessment of MON810. The environmental risk assessment of the maize MON810 is based on information provided by the applicant in the notification C/F/95/12/02 and application EFSA/GMO/RX/MON810, and scientific comments from EFSA and other member states made available on the EFSA website GMO Extranet. The risk assessment also considered other peer-reviewed scientific literature as relevant. The VKM GMO Panel has evaluated MON810 with reference to its intended uses in the European Economic Area (EEA), and according to the principles described in the Norwegian Food Act, the Norwegian Gene Technology Act and regulations relating to impact assessment pursuant to the Gene Technology Act, Directive 2001/18/EC on the deliberate release into the environment of genetically modified organisms, and Regulation (EC) No 1829/2003 on genetically modified food and feed. The Norwegian Scientific Committee for Food Safety has also decided to take account of the appropriate principles described in the EFSA guidelines for the risk assessment of GM plants and derived food and feed (EFSA 2006, 2011a), the environmental risk assessment of GM plants (EFSA 2010), the selection of comparators for the risk assessment of GM plants (EFSA 2011b), and for the post-market environmental monitoring of GM plants (EFSA 2006, 2011c). The scientific risk assessment of maize MON810 include molecular characterisation of the inserted DNA and expression of the target protein, comparative assessment of agronomic and phenotypic characteristics, unintended effects on plant fitness, potential for gene transfer, interactions between the GM plant and target and non-target organisms, effects on biogeochemical processes and evaluations of the post-market environmental plan. In line with its mandate, VKM emphasised that assessments of sustainable development, societal utility and ethical considerations, according to the Norwegian Gene Technology Act and Regulations relating to impact assessment pursuant to the Gene Technology Act, shall not be carried out by the Panel on Genetically Modified Organisms. The genetically modified maize MON810 was developed to provide protection against certain lepidopteran target pests, including European corn borer (Ostrinia nubilalis) and species belonging to the genus Sesamia. Protection is achieved through expression in the plant of the insecticidal Cry protein, Cry1Ab, derived from Bacillus thuringiensis ssp. kurstaki, a common soil bacterium. Molecular characterisation Appropriate analysis of the integration site including flanking sequences and bioinformatics analyses have been performed to analyse the construct integrated in the GM plant. Updated bioinformatics analyses revealed that one ORF shared sequence similarity to a putative HECT-ubiquitin ligase protein. The VKM GMO Panel found no safety implications from the interruption of this gene sequence. Analyses of leaf, grains, whole plant tissue and pollen from the maize MON 810 demonstrated that the Cry1Ab protein is expressed at very low levels in all tissues tested and constitutes less than 0.001% of the fresh weight in each tissue. The cry1Ab gene is the only transgene expressed in line MON 810 and was expressed highest in the leaves. The stability of the genetic modification has been demonstrated over several generations. Event MON810 and the physical, chemical and functional characteristics of the proteins have previously been evaluated by The VKM Panel on Genetically Modified Organisms, and considered satisfactory (VKM 2007a,b). Comparative assessment: Comparative analyses of data from field trials located at representative sites and environments in the USA and Europe indicate that maize MON810 is agronomically and phenotypically equivalent to the conventional counterpart and commercially available reference varieties, with the exception of the lepidopteran-protection trait, conferred by the expression of the Cry1Ab protein. The field evaluations support a conclusion of no phenotypic changes indicative of increased plant weed/pest potential of MON810 compared to conventional maize. Evaluations of ecological interactions between maize MON810 and the biotic and abiotic environment indicate no unintended effects of the introduced trait on agronomic and phenotypic characteristics. Environmental risk: There are no reports of the target lepidopteran species attaining pest status on maize in Norway. Since there are no Bt-based insecticides approved for use in Norway, and lepidopteran pests have not been registered in maize, issues related to resistance evolution in target pests are not relevant at present for Norwegian agriculture. Published scientific studies show no or negligible adverse effects of Cry1Ab protein on non-target arthropods that live on or in the vicinity of maize plants. Cultivation of maize MON810 is not considered to represent a threat to the prevalence of red-listed species in Norway. Few studies have been published examining potential effects of Cry1Ab toxin on ecosystems in soil, mineralization, nutrient turnover and soil communities. Some field studies have indicated that root exudates and decaying plant material containing Cry proteins may affect population size and activity of rhizosphere organisms (soil protozoa and microorganisms). Most studies conclude that effects on soil microorganisms and microbial communities are transient and minor compared to effects caused by agronomic and environmental factors. However, data are only available from short term experiments and predictions of potential long term effects are difficult to deduce. Few studies have assessed the impact of Cry proteins on non-target aquatic arthropods and the fate of these proteins in senescent and decaying maize detritus in aquatic environments. However, exposure of non-target organisms to Cry proteins in aquatic ecosystems is likely to be very low, and potential exposure of Bt toxins to non-target organisms in aquatic ecosystems in Norway is considered to be negligible. Maize is the only representative of the genus Zea in Europe, and there are no cross-compatible wild or weedy relatives outside cultivation with which maize can hybridise and form backcross progeny. Vertical gene transfer in maize therefore depends on cross-pollination with other conventional or organic maize varieties. In addition, unintended admixture of genetically modified material in seeds represents a possible way for gene flow between different crop cultivations. The risk of pollen flow from maize volunteers is negligible under Norwegian growing conditions. In addition to the data presented by the applicant, the VKM GMO Panel is not aware of any scientific report of increased establishment and spread of maize MON810 and any change in survival (including over-wintering), persistence and invasiveness capacity. Because the general characteristics of maize MON810 are unchanged, insect resistance are not likely to provide a selective advantage outside cultivation in Norway. Since MON810 has no altered agronomic and phenotypic characteristics, except for the specific target pest resistance, the VKM GMO Panel is of the opinion that the likelihood of unintended environmental effects due to the establishment and survival of maize MON810 will be no different to that of conventional maize varieties in Norway. Overall conclusion: The VKM GMO Panel concludes that cultivation of maize MON810 is unlikely to have any adverse effect on the environment in Norway.

Global climate models have circulation biases that the community aims to reduce, for instance through high‐resolution dynamical downscaling. We used the Weather Research and Forecasting model (WRF) to downscale both ERA‐Interim and a bias‐corrected version of the Norwegian climate model NorESM1‐M on a high‐resolution grid. By varying the domain size, we investigated the influence of the driving data and highly resolved topography on the North Atlantic storm track and the precipitation in its exit region. In our largest domains, we found large‐scale circulation and storm track biases similar to those seen in global models and with spatial patterns independent of the driving data. The biases in the smaller domains were more dependent on the quality of the driving data. Nevertheless, the biases had little effect on the simulated precipitation in Norway. Although the added value of downscaling was clear with respect to the global climate models, all the downscaled simulations showed similar precipitation frequencies and intensities. We posit that, because the precipitation is so strongly governed by the local topographic forcing, a correct storm track is less critical for the precipitation distribution. publishedVersion

A new high-resolution (3 km) numerical mesoscale weather simulation spanning the period 2004–2018 is validated for offshore wind power purposes for the North Sea and Norwegian Sea. The NORwegian hindcast Archive (NORA3) was created by dynamical downscaling, forced with state-of-the-art hourly atmospheric reanalysis as boundary conditions. A validation of the simulated wind climatology has been carried out to determine the ability of NORA3 to act as a tool for planning future offshore wind power installations. Special emphasis is placed on evaluating offshore wind power-related metrics and the impact of simulated wind speed deviations on the estimated wind power and the related variability. The general conclusion of the validation is that the NORA3 data is rather well suited for wind power estimates, but gives slightly conservative estimates on the offshore wind metrics. Wind speeds are typically 5 % (0.5 ms−1) lower than observed wind speeds, giving an underestimation of offshore wind power of 10 %–20 % (equivalent to an underestimation of 3 percentage point in the capacity factor), for a selected turbine type and hub height. The model is biased towards lower wind power estimates because of overestimation of the frequency of low-speed wind events (< 10 ms−1) and underestimation of high-speed wind events (> 10 ms−1). The hourly wind speed and wind power variability are slightly underestimated in NORA3. However, the number of hours with zero power production (around 12 % of the time) is fairly well captured, while the duration of each of these events is slightly overestimated, leading to 25-year return values for zero-power duration being too high for four of the six sites. The model is relatively good at capturing spatial co-variability in hourly wind power production among the sites. However, the observed decorrelation length was estimated to be 432 km, whereas the model-based length was 19 % longer.

Communication is an increasing prerequisite to justify academic existence and value, and for project funding of all kinds to show relevance and value, including the future of European networks like COST Actions. Academia is slowly adapting to this expectation and learning the profession of communication. Language and vocabulary are key issues in communication, and particularly to reach the many important non-scientific audiences. Therefore, this chapter starts with a description of some new plant breeding technologies relevant for communicating, in general terms, the science behind plant improvement. This is followed by selected examples of the application of these techniques to improve current and future crop varieties. Finally, key messages gathered from the European iPLANTA project for policy makers, non-specialists and specially interested citizens are communicated. This is to show a wider audience how RNAi can contribute to sustainable food solutions and food security with minimal environmental impacts.

We use a dataset with observations of daily precipitation from 55 homogeneity tested stations in Norway over the period 1900-2019 available from MET-Norway. These observations show that precipitation in Norway has increased monotonically by 19% since 1900. Notably, over half of the overall increase was recorded within the decade of 1980-1990. To examine possible mechanisms behind the precipitation increase, we use a diagnostic model to separate the effects of changes in vertical velocity, temperature and relative humidity. We use vertical velocity, near-surface temperature and relative humidity from two reanalysis products, ECMWF’s ERA-20C and NOAA’s 20th Century Reanalysis. The model-based precipitation estimates capture the interannual variability as well as the long-term trend, but the absolute magnitude of precipitation is underestimated. Within our model, we find that the variability in vertical velocity chiefly determines the interannual variability and long-term trends. In fact, the trend in vertical velocities contributes with more than 75% of the total modelled trend in precipitation between 1900-2019, and more than 60% of the anomalies between 1980-1990. However, over the last decades (1979 to 2019), changes in temperature and relative humidity are the main contributors to the trend. Thus, different physical processes shape the trend at different times. We hypothesize that the strong precipitation increase in the 1980’s is linked to an unusual high number of low pressure systems reaching Norway from the North-Atlantic. In recent decades, direct effects of global warming (rising temperatures and hence increased water vapour content) are thought to be the main cause of the positive trend in precipitation over Norway.

Background Dural arteriovenous fistulae are among the most common causes of pulsatile tinnitus. Selective angiography can be necessary for a definitive diagnosis, but in rare cases has been reported to cause sudden cortical blindness. Case presentation We present a woman in her seventies for whom cerebral angiography revealed a dural arteriovenous fistula. Two hours after the angiography she experienced sudden bilateral blindness. A local cause of sudden visual loss was excluded by clinical examination, cerebral bleeding was excluded by CT scan, vascular spasms and occlusions were excluded by CT angiography and acute infarction over the bilateral parieto-occipital cortex was excluded by MRI. The CT scan did, however, show contrast enhancement in the visual cortex from the contrast given during the previously performed cerebral angiography. The patient's vision spontaneously recovered within six days after the angiography, with no residual neurological deficits in her subsequent clinical follow up. Surgery was later performed on her dural arteriovenous fistula, which successfully treated the pulsatile tinnitus. Interpretation Transient cortical blindness is a rare but dramatic complication after cerebral angiography, thought to be caused by the transient neurotoxic effects of iodine-containing contrast agents. When other causes of sudden blindness are excluded, the patient can be reassured about the excellent prognosis for this condition.

Neuroblastoma (NB) is a childhood cancer with a highly complex nature. High-risk NB patients undergo intensive treatment regimens that are often followed by long-term side effects. This, in addition to the emergence of resistant cancer cells, highlights a need for novel therapeutic targets and treatment strategies to improve outcome in NB. P21 is a cyclin-dependent kinase inhibitor considered to play a role in tumor resistance and aggressiveness due to its involvement in cell cycle and/or apoptosis. This project aimed to explore the expression of endogenous p21 in high-risk NB cell lines and whether p21 could be a therapeutic target for high-risk NB. Endogenous p21 levels were investigated using RT-qPCR and quantitative immunocytochemistry in eight high-risk NB cell lines. A small molecular inhibitor of p21, UC2288, was used in these cell lines to investigate tumour cell viability following p21 inhibition. In addition, combination treatment with UC2288 and the chemotherapy drug cisplatin was performed on resistant NB cell lines. Our results show variable expression of p21, where cell lines with high endogenous p21 expression showed sensitivity to single agent treatment with cisplatin or UC2288. Moreover, resistant NB cell lines showed lower endogenous p21 expression, however, combination treatment with UC2288 and cisplatin showed reduced viability, indicating sensitivity to combination treatment. This project highlights the potential of using p21 as a therapeutic target as well as a predictive biomarker in high-risk NB.

Careful brain monitoring saves lives and is beneficial to patients' health. Nevertheless, Norway lacks guidelines for brain monitoring in hospitals.

International audience

Carnation SHD-27531-4 is a genetically modified variety of Dianthus caryophyllus L. used as a decorative plant species. The red-purple colour of the flowers results from expression of the two newly introduced genes dfr and f 3’5’h, encoding the enzymes dihydroflavonol 4reductase (DFR) and flavonoid 3’,5’-hydroxylase (F3’5’H). The two enzymes enable the production of the pigments delphinidin and cyanidin (anthocyanidins) in the flower petals. Anthocyanidins and their sugar derivatives, anthocyanins, make up a large group of natural colours and are accepted food additives (E 163). The colours of most flowers, berries and fruits consist of a combination of anthocyanidins and anthocyanins. Carnation line SHD-27531-4 also contains a mutated herbicide tolerance gene from Nicotiana tabacum , coding for an acetolactate synthase (ALS) variant protein, used to facilitate the selection of GM plantlets during the genetic transformation process. Southern blot analysis and sequencing indicate only a single copy of the intended T-DNA insert in the SHD-27531-4 genome. Flanking sequences show no disruption of endogenous genes. In silico analyses show no significant homologies between the DFR, F3’5’H an ALS proteins and known toxins and IgE-bound allergens. No observed changes in the introduced trait, i.e. the particular flower colour, indicative of instability, have been reported during several generations of vegetatively propagated plants. Considering that carnation SHD-27531-4 is not intended for cultivation or use as food or feed, the VKM GMO Panel considers the comparative analysis of the anthocyanidins delphinidin, cyanidin, petunidin and pelargonidin in the flower petals sufficient for the risk assessment. The reported morphological differences between SHD-27531-4 and the parent cultivar do not raise safety concerns. Based on current knowledge and the scope of the application, the VKM GMO Panel concludes that the DFR, F3’5’H and ALS proteins and anthocyanidin pigments are unlikely to increase a potential health risk related to an accidental intake or other exposure routes to carnation SHD-27531-4 compared to the conventional counterpart or other non-GM carnations. Likewise, the VKM GMO Panel concludes that carnation SHD-27531-4, based on current knowledge and the intended use as cut ornamental flowers, does not represent an environmental risk in Norway.

Guidelines state that patients with aneurysmal subarachnoid haemorrhage (aSAH) require neurosurgical treatment as early as possible. Little is known about the time frame of transport from the ictus scene to Neurosurgery in large, partially remote catchment areas. We therefore analysed the chronology and transport logistics of aSAH patients in the South-Eastern Norway Health Region and related them to the frequency of aneurysm rebleed and 1-year mortality. Retrospective analysis of aSAH patients bleeding within our region admitted to Neurosurgery during a 5-year period. Date, time and site of ictus and arrival at Neurosurgery, distance and mode of transport and admission were obtained from our institutional quality register and the emergency medical communication centre log. We scored the patients’ clinical condition, rebleeds and 1-year mortality. Five hundred forty-four patients were included. Median time from ictus to arrival Neurosurgery was 4.5 h. Transport by road ambulance was most common at distances between the ictus scene and Neurosurgery below 50 km, whereas airborne transport became increasingly more common at larger distances. Direct admissions, frequency of intubation and airborne transport to Neurosurgery increased with the severity of haemorrhage, leading to shorter transport times. The risk of rebleed was 0.8%/hour of transport. The rebleed rate was independent of distances travelled, but increased with the severity of aSAH, reaching up to 6.54%/hour in poor-grade patients. Distance and time of transport had no impact on 1-year mortality, whereas poor-grade aSAH and rebleed were strong predictors of mortality. Poor-grade aSAH patients have a high risk of rebleed independent of the distance between the ictus scene and Neurosurgery. As rebleeding triples 1-year mortality, patients with Glasgow Coma Score