FAIRMODE: A FORUM FOR AIR QUALITY MODELLING IN EUROPE

FAIRMODE (Forum for AIR quality MODelling in Europe) is an air quality modelling network that was established as a joint initiative of the European Environment Agency (EEA) and European Commission’s Joint Research Centre (JRC). In a common effort EEA and JRC aim at responding to the requirements of the new Air Quality Directive, with particular focus on the introduction of modelling as a necessary tool for air quality assessment and air quality management. The main aim of the modelling network is to bring together air quality modellers and model users in order to promote and support harmonised use of modelling for the assessment of air quality by EU and EEA member countries. The network will thus encourage synergy – at a local, national and European level - through the development and implementation of a common infrastructure based on best practices for reporting and storing information relevant to air quality modelling. A major objective of the FAIRMODE initiative is to provide guidance to present and future air quality model users in EEA’s EIONET partnership network. FAIRMODE also aims to enhance awareness of model usefulness, reliability and accuracy through model validation and intercomparison exercises at a national or European level. The JRC has taken on a leading role in the co-ordination of the latter activities gaining from its experience in leading the “Eurodelta” and “CityDelta” intercomparison exercises. A centralised web portal has been created in support of FAIRMODE, which is currently being used for internal communication purposes of the network participants, but will also provide the means for exchange of relevant material and experiences between all interested modellers and model users. The initial activities of the network will be organised by two main Work Groups, focusing on the preparation of a Guidance Document for model use and on model QA/QC procedures (input data, other uncertainties) respectively. The progress of the preparation of these documents as well as of the rest of the regular activities of the network will be reviewed and discussed within the frame of annual Plenary meetings and Steering Committee meetings

A Piglet Model for Detection of Hypoxic-Ischemic Brain Injury with Magnetic Resonance Imaging

Munkeby BH, de Lange C, Emblem KE, Bjørnerud A, Kro GAB, Andresen J, Winther-Larssen EH, Løberg EM, Hald JK. A piglet model for detection of hypoxic-ischemic brain injury with magnetic resonance imaging. Acta Radiol 2008;49:1049–1057

γ-Secretase modulators show selectivity for γ-secretase–mediated amyloid precursor protein intramembrane processing

The aggregation of β-amyloid peptide 42 results in the formation of toxic oligomers and plaques, which plays a pivotal role in Alzheimer's disease pathogenesis. Aβ42 is one of several Aβ peptides, all of Aβ30 to Aβ43 that are produced as a result of γ-secretase–mediated regulated intramembrane proteolysis of the amyloid precursor protein. γ-Secretase modulators (GSMs) represent a promising class of Aβ42-lowering anti-amyloidogenic compounds for the treatment of AD. Gamma-secretase modulators change the relative proportion of secreted Aβ peptides, while sparing the γ-secretase–mediated processing event resulting in the release of the cytoplasmic APP intracellular domain. In this study, we have characterized how GSMs affect the γ-secretase cleavage of three γ-secretase substrates, E-cadherin, ephrin type A receptor 4 (EphA4) and ephrin type B receptor 2 (EphB2), which all are implicated in important contexts of cell signalling. By using a reporter gene assay, we demonstrate that the γ-secretase–dependent generation of EphA4 and EphB2 intracellular domains is unaffected by GSMs. We also show that γ-secretase processing of EphA4 and EphB2 results in the release of several Aβ-like peptides, but that only the production of Aβ-like proteins from EphA4 is modulated by GSMs, but with an order of magnitude lower potency as compared to Aβ modulation. Collectively, these results suggest that GSMs are selective for γ-secretase–mediated Aβ production

Aspiration–sclerotherapy Results in Effective Control of Liver Volume in Patients with Liver Cysts

Purpose To study the extent to which aspiration–sclerotherapy reduces liver volume and whether this therapy results in relief of symptoms. Results Four patients, group I, with isolated large liver cysts, and 11 patients, group II, with polycystic livers, underwent aspiration–sclerotherapy. Average volume of aspirated cyst fluid was 1,044 ml (range 225–2,000 ml) in group I and 1,326 ml (range 40–4,200 ml) in group II. Mean liver volume before the procedure was 2,157 ml (range 1,706–2,841 ml) in group I and 4,086 ml (range 1,553–7,085 ml) in group II. This decreased after the procedure to 1,757 ml (range 1,479–2,187 ml) in group I. In group II there was a statistically significant decrease to 3,347 ml (range 1,249–6,930 ml, P = 0.008). Volume reduction was 17.1% (range −34.7% to −4.1%) and 19.2% (range −53.9% to +2.4%) in groups I and II, respectively. Clinical severity of all symptoms decreased, except for involuntary weight loss and pain in group II. Conclusion Aspiration–sclerotherapy is an effective means of achieving liver volume reduction and relief of symptoms

First Steps towards Underdominant Genetic Transformation of Insect Populations

The idea of introducing genetic modifications into wild populations of insects to stop them from spreading diseases is more than 40 years old. Synthetic disease refractory genes have been successfully generated for mosquito vectors of dengue fever and human malaria. Equally important is the development of population transformation systems to drive and maintain disease refractory genes at high frequency in populations. We demonstrate an underdominant population transformation system in Drosophila melanogaster that has the property of being both spatially self-limiting and reversible to the original genetic state. Both population transformation and its reversal can be largely achieved within as few as 5 generations. The described genetic construct {Ud} is composed of two genes; (1) a UAS-RpL14.dsRNA targeting RNAi to a haploinsufficient gene RpL14 and (2) an RNAi insensitive RpL14 rescue. In this proof-of-principle system the UAS-RpL14.dsRNA knock-down gene is placed under the control of an Actin5c-GAL4 driver located on a different chromosome to the {Ud} insert. This configuration would not be effective in wild populations without incorporating the Actin5c-GAL4 driver as part of the {Ud} construct (or replacing the UAS promoter with an appropriate direct promoter). It is however anticipated that the approach that underlies this underdominant system could potentially be applied to a number of species. Figure

Patient-reported outcomes in palliative gastrointestinal stenting: a Norwegian multicenter study

Background The clinical effect of stent treatment has been evaluated by mainly physicians; only a limited number of prospective studies have used patient-reported outcomes for this purpose. The aim of this work was to study the clinical effect of self-expanding metal stents in treatment of malignant gastrointestinal obstructions, as evaluated by patient-reported outcomes, and compare the rating of the treatment effect by patients and physicians. Methods Between November 2006 and April 2008, 273 patients treated with SEMS for malignant GI and biliary obstructions were recruited from nine Norwegian hospitals. Patients and physicians assessed symptoms independently at the time of treatment and after 2 weeks using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire supplemented with specific questions related to obstruction. Results A total of 162 patients (99 males; median age = 72 years) completed both assessments and were included in the study. A significant improvement in the mean global health score was observed after 2 weeks (from 9 to 18 on a 0–100 scale, P\0.03) for all stent locations. Both patients and physicians reported a significant reduction in all obstruction-related symptoms ([20 on the 0–100 scale, P\0.006) after SEMS treatment. The physicians reported a larger mean improvement in symptoms than did the patients, mainly because they reported more severe symptoms before treatment. Conclusion SEMS treatment is effective in relieving symptoms of malignant GI and biliary obstruction, as reported by patients and physicians. The physicians, however, reported a larger reduction in obstructive symptoms than did the patients. A prospective assessment of patientreported outcomes is important in evaluating SEMS treatment

Interdigital dermatitis, heel horn erosion, and digital dermatitis in 14 Norwegian dairy herds

AbstractThe aim of this study was to assess infectious foot diseases, including identification and characterization of Dichelobacter nodosus and Treponema spp., in herds having problems with interdigital dermatitis (ID) and heel horn erosion (E) and in control herds expected to have few problems. We also wanted to compare diseased and healthy cows in all herds. The study included 14 dairy herds with a total of 633 cows. Eight herds had a history of ID and E, and 6 were control herds. All cows were scored for lameness, and infectious foot diseases on the hind feet were recorded after trimming. Swabs and biopsies were taken from the skin of 10 cows in each herd for bacterial analyses. In total, samples were taken from 34 cows with ID, 11 with E, 40 with both ID and E, and 8 with digital dermatitis (DD), and from 47 cows with healthy feet. Swabs were analyzed for identification and characterization of D. nodosus by PCR, culture, virulence testing, and serotyping. Biopsies were analyzed by fluorescent in situ hybridization regarding histopathology, identification, and characterization of Treponema spp., and identification of D. nodosus. Interdigital dermatitis was the most frequent foot disease, with a prevalence of 50.4% in problem herds compared with 26.8% in control herds. Heel horn erosion was recorded in 34.8% of the cows in problem herds compared with 22.1% in control herds. Dichelobacter nodosus was detected in 97.1% of the cows with ID, in 36.4% with E, in all cows with both ID and E, in all cows with DD, and in 66.0% of cows with healthy feet. All serogroups of D. nodosus except F and M were detected, and all isolates were defined as benign by the gelatin gel test. Treponema spp. were detected in 50.0% of the cows with ID, in 9.1% with E, in 67.5% with ID and E, in all cows with DD, and in 6.4% of those with healthy feet. In total, 6 previously described phylotypes (PT) of Treponema were detected: PT1, PT3, PT6, PT13, and PT15 in cows with ID, PT1 in a cow with E, and PT1, PT2, PT3, PT6, and PT13 in cows with both ID and E. One new phylotype (PT19) was identified. The epidermal damage score was higher but the difference in inflammatory response of the dermis was minor in cows with ID versus those with healthy feet. Fisher’s exact test revealed an association between ID and D. nodosus, and between ID and Treponema spp. Logistic regression revealed an association between both ID and E and dirty claws (odds ratios=1.9 and 2.0, respectively). Our study indicates that D. nodosus, Treponema spp., and hygiene are involved in the pathogenesis of ID

Quantification of Alternative Splicing Variants of Human Telomerase Reverse Transcriptase and Correlations with Telomerase Activity in Lung Cancer

Telomerase plays important roles in the development and progression of malignant tumors, and its activity is primarily determined by transcriptional regulation of human telomerase reverse transcriptase (hTERT). Several mRNA alternative splicing variants (ASVs) for hTERT have been identified, but it remains unclear whether telomerase activity is directly associated with hTERT splicing transcripts. In this study, we developed novel real-time PCR protocols using molecular beacons and applied to lung carcinoma cell lines and cancerous tissues for quantification of telomerase activity and three essential hTERT deletion transcripts respectively. The results showed that lung carcinoma cell lines consistently demonstrated telomerase activity (14.22–31.43 TPG units per 100 cells) and various hTERT alternative splicing transcripts. For 165 lung cancer cases, telomerase activity showed significant correlation with tumor differentiation (poorly->moderately->well-differentiated, P<0.01) and with histotypes (combined small cell and squamous cell carcinoma>squamous cell carcinoma>adenosquamous carcinoma>adenocarcinoma, P<0.05). Although the overall hTERT transcripts were detected in all the samples, they were not associated with telomerase activity (r = 0.092, P = 0.24). Telomerase activity was significantly correlated with the transcriptional constituent ratio of α-deletion (r = -0.267, P = 0.026), β-deletion (r = -0.693, P = 0.0001) and γ-deletion (r = –0.614, P = 0.001). The positive rate and average constituent ratio of β-deletion transcripts (92.12%, 0.23) were higher than those of α-deletion (41.82%, 0.12) or γ-deletion (16.36%, 0.18) transcripts. The combined small-cell and squamous cell carcinomas expressed less deletion transcripts, especially β-deletion, than other histotypes, which might explain their higher telomerase activity. In conclusion, the molecular beacon-based real-time PCR protocols are rapid, sensitive and specific methods to quantify telomerase activity and hTERT ASVs. Telomerase activity may serve as a reliable and effective molecular marker to assist the evaluation of histological subtype and differentiation of lung carcinomas. Further studies on hTERT deletion splicing transcripts, rather than the overall hTERT transcripts, may improve our understanding of telomerase regulation