A comparison of atmospheric transport models for traffic emissions

De in Nederland gebruikte rekenmodellen voor luchtkwaliteit langs snelwegen en stadswegen geven wisselende resultaten. Voor berekening van jaargemiddelde concentraties van stikstofdioxide en fijn stof zijn de verschillen tussen modellen beperkt. Bij de berekening van meer specifieke aspecten van luchtkwaliteit, bijvoorbeeld het aantal overschrijdingsdagen, kunnen de verschillen tussen modelresultaten aanzienlijk groter zijn. Atmosferische verspreidingsmodellen berekenen luchtkwaliteit als gevolg van emissies door het verkeer. In Nederland is een aantal van deze verspreidingsmodellen in gebruik bij overwegend commerciele bureaus. Zij voeren berekeningen uit in opdracht van overheid en bedrijfsleven. De rekenmodellen die deze bureaus gebruiken werken volgens uiteenlopende rekenmethoden. Om vast te stellen in hoeverre de resultaten van de verschillende modellen met elkaar overeenstemmen, zijn in dit onderzoek zes in Nederland gebruikte rekenmodellen met elkaar vergeleken. Bij de berekening van de jaargemiddelde concentratie van stikstofdioxide en fijn stof langs snel- en stadswegen, liggen de resultaten van de modellen binnen een marge van 10-15% rond het gemiddelde van de modellen. Bij de berekening van het aantal overschrijdingsdagen voor fijn stof langs snelwegen liggen de verschillende modelresultaten echter in een bandbreedte van 30% rond het gemiddelde. Voor een typische stadswegsituatie is die bandbreedte 50%.This report presents the results of an intercomparison study of six atmospheric transport models for traffic situations in the Netherlands. A number of test cases were defined in consultation with the model owners in which the input parameters to the models, such as emissions, meteorological conditions and road characteristics. Two base cases were defined: one for roadways and one for urban roads, along with a number of variants on these two base cases. The variants, for example, consisted of different meteorological conditions, different background concentrations and the presence of a noise barrier. The model owners calculated - for both base cases and variants - the annual concentration of NO2 and PM10 and the number of days in which the daily threshold of 50 ug/m3 of PM10 is exceeded. For the roadway test cases annual levels of NO2 and PM10 calculated by the different models are within about 10% of the average of all model results. The large difference found in the number of exceedence days was caused by the difference in the methods used to derive the exceedence days. When using one standard method, as in the Dutch regulations, this difference fell to within 30%. Because of technical reasons only the "street canyon" variant was considered for urban roads. In this variant the model results were between 10% and 15% for NO2 and PM10, respectively, of the average of all models. If the contribution of the road alone is considered (i.e. comparing the concentrations without the prescribed background concentration), the models differ by a factor of 2 to 3 and the number of exceedence days for PM10 by a factor of 2.VROM-DG

A comparison between concentrations calculated with CAR II 5.0 and concentrations measured via the air quality network

Lokale overheden gebruiken het model CAR II (Calculation of Air pollution from Road traffic) voor de berekening van de luchtkwaliteit in verkeersbelaste situaties. Uit onderzoek van het RIVM blijkt dat de berekende stikstofdioxide en fijn stof concentraties redelijk goed overeen komen met metingen. De berekende concentraties zijn gemiddeld enkele microgrammen per kubieke meter hoger respectievelijk lager dan de gemeten stikstofdioxide en fijn stof concentraties. Op basis van door gemeenten zelf aangeleverde verkeersgegevens zijn voor de jaren 2003, 2004 en 2005 berekeningen met CAR II, versie 5.0, uitgevoerd in de straten waar meetstations van het van het Landelijk Meetnet Luchtkwaliteit van het RIVM staan. De resultaten van de berekeningen voor stikstofdioxide en fijn stof zijn vervolgens vergeleken met metingen in de straten over dezelfde periode. De berekende stikstofdioxide concentraties zijn gemiddeld ruim twee microgram per kubieke meter hoger dan de gemeten concentraties. De berekende fijn stof concentraties zijn gemiddeld iets lager dan de gemeten concentraties. Er is voor fijn stof een grotere spreiding in de geconstateerde verschillen dan voor stikstofdioxide het geval is. De resultaten van CAR II voldoen voor de jaargemiddelde concentratie van zowel stikstofdioxide als fijn stof aan de in de wet gestelde eisen voor de nauwkeurigheid van de bepaling van jaargemiddelde concentraties. In hoeverre de resultaten van de uitgevoerde vergelijking een garantie zijn voor de betrouwbaarheid en/of de toepasbaarheid van CAR voor toekomstige jaren is moeilijk te zeggen. Het is niet onmogelijk dat verschillende bouwstenen in de huidige CAR onvolkomenheden bevatten die elkaar nu (deels) compenseren.Dutch municipalities use the model CAR II (Calculation of Air pollution from Road traffic) to estimate local air quality in streets with traffic. RIVM has shown that the concentrations of nitrogen dioxide and particulate matter, as calculated by CAR II, version 5.0, are in fairly good agreement with measurements. Calculated concentrations are, on average, a few micrograms per cubic metre higher (for nitrogen dioxide) or lower (for particulate matter) compared to measurements. Based on traffic information provided by municipalities, calculations were performed using CAR II, version 5.0, for the years 2003, 2004 and 2005 for those streets where a measuring station of the national air quality measuring network of the RIVM is located. The results of the calculations were compared with measurements during the same period. Calculated nitrogen dioxide concentrations are on average just over two micrograms per cubic metre higher than measured concentrations. For particulate matter the calculated concentrations are just below measured levels. Furthermore, the spread in differences between measured and calculated concentrations is larger for particulate matter. With respect to accuracy of the calculations, the yearly averaged concentrations calculated by CAR II comply with legal regulations. It will be difficult to determine to what extent the results of the present study can be used to indicate the reliability and applicability of the CAR model in future. It is also quite possible that several modules of CAR contain errors, which, at present, counteract each other.VROM-LM

Memantine: Can it be Used to Treat Children with Autism Spectrum Disorder?

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in social, behavior and communicative skills. The current therapy for ASD only targets the associated symptoms such as aggression, self-harming acts or temper tantrums but not the core symptoms of social dysfunction. The pathology of ASD is not fully understood. Interestingly, imaging studies in ASD patients have reported abnormal high levels of glutamate in certain brain regions that play an important role in social interaction and communication. Thus, it has been hypothesized that medications attenuating glutamate transmission may be used as treatment for some of the core symptoms of ASD. Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been approved for the treatment of Alzheimer\u27s disease, and has shown promise in alleviating some of the symptoms of ASD in children. In this review, we will discuss the pathology of ASD, findings from studies that evaluated memantine in ASD patients, the adverse effects of memantine and the potential use of memantine in the treatment of ASD. Finally, we will discuss the role of the pharmacist in managing patients with ASD

Characterising the motion and cardiorespiratory interaction of preterm infants can improve the classification of their sleep state

Aim This study aimed to classify quiet sleep, active sleep and wake states in preterm infants by analysing cardiorespiratory signals obtained from routine patient monitors. Methods We studied eight preterm infants, with an average postmenstrual age of 32.3 ± 2.4 weeks, in a neonatal intensive care unit in the Netherlands. Electrocardiography and chest impedance respiratory signals were recorded. After filtering and R-peak detection, cardiorespiratory features and motion and cardiorespiratory interaction features were extracted, based on previous research. An extremely randomised trees algorithm was used for classification and performance was evaluated using leave-one-patient-out cross-validation and Cohen's kappa coefficient. Results A sleep expert annotated 4731 30-second epochs (39.4 h) and active sleep, quiet sleep and wake accounted for 73.3%, 12.6% and 14.1% respectively. Using all features, and the extremely randomised trees algorithm, the binary discrimination between active and quiet sleep was better than between other states. Incorporating motion and cardiorespiratory interaction features improved the classification of all sleep states (kappa 0.38 ± 0.09) than analyses without these features (kappa 0.31 ± 0.11). Conclusion Cardiorespiratory interactions contributed to detecting quiet sleep and motion features contributed to detecting wake states. This combination improved the automated classifications of sleep states

Tumor-educated Tregs drive organ-specific metastasis in breast cancer by impairing NK cells in the lymph node niche

Breast cancer is accompanied by systemic immunosuppression, which facilitates metastasis formation, but how this shapes organotropism of metastasis is poorly understood. Here, we investigate the impact of mammary tumorigenesis on regulatory T cells (Tregs) in distant organs and how this affects multi-organ metastatic disease. Using a preclinical mouse mammary tumor model that recapitulates human metastatic breast cancer, we observe systemic accumulation of activated, highly immunosuppressive Tregs during primary tumor growth. Tumor-educated Tregs show tissue-specific transcriptional rewiring in response to mammary tumorigenesis. This has functional consequences for organotropism of metastasis, as Treg depletion reduces metastasis to tumor-draining lymph nodes, but not to lungs. Mechanistically, we find that Tregs control natural killer (NK) cell activation in lymph nodes, thereby facilitating lymph node metastasis. In line, an increased Treg/NK cell ratio is observed in sentinel lymph nodes of breast cancer patients compared with healthy controls. This study highlights that immune regulation of metastatic disease is highly organ dependent

Fractional anisotropy in white matter tracts of very-low-birth-weight infants

Background: Advances in neonatal intensive care have not yet reduced the high incidence of neurodevelopmental disability among very-low-birth-weight (VLBW) infants. As neurological deficits are related to white-matter injury, early detection is important. Diffusion tensor imaging (DTI) could be an excellent tool for assessment of white-matter injury. Objective: To provide DTI fractional anisotropy (FA) reference values for white-matter tracts of VLBW infants for clinical use. Materials and methods: We retrospectively analysed DTI images of 28 VLBW infants (26-32 weeks gestational age) without evidence of white-matter abnormalities on conventional MRI sequences, and normal developmental outcome (assessed at age 1-3 years). For DTI an echoplanar sequence with diffusion gradient (b = 1,000 s/mm2) applied in 25 non-collinear directions was used. We measured FA and apparent diffusion coefficient (ADC) of different white-matter tracts in the first 4 days of life. Results: A statistically significant correlation was found between gestational age and FA of the posterior limb of the internal capsule in VLBW infants (r = 0.495, P<0.01). Conclusion: Values of FA and ADC were measured in white-matter tracts of VLBW infants. FA of the pyramidal tracts measured in the first few days after birth is related to gestational age

Structural basis for CRISPR RNA-guided DNA recognition by Cascade

The CRISPR (clustered regularly interspaced short palindromic repeats) immune system in prokaryotes uses small guide RNAs to neutralize invading viruses and plasmids. In Escherichia coli, immunity depends on a ribonucleoprotein complex called Cascade. Here we present the composition and low-resolution structure of Cascade and show how it recognizes double-stranded DNA (dsDNA) targets in a sequence-specific manner. Cascade is a 405-kDa complex comprising five functionally essential CRISPR-associated (Cas) proteins (CasA1B2C6D1E1) and a 61-nucleotide CRISPR RNA (crRNA) with 5′-hydroxyl and 2′,3′-cyclic phosphate termini. The crRNA guides Cascade to dsDNA target sequences by forming base pairs with the complementary DNA strand while displacing the noncomplementary strand to form an R-loop. Cascade recognizes target DNA without consuming ATP, which suggests that continuous invader DNA surveillance takes place without energy investment. The structure of Cascade shows an unusual seahorse shape that undergoes conformational changes when it binds target DNA.

Phage-Induced Expression of CRISPR-Associated Proteins Is Revealed by Shotgun Proteomics in Streptococcus thermophilus

The CRISPR/Cas system, comprised of clustered regularly interspaced short palindromic repeats along with their associated (Cas) proteins, protects bacteria and archaea from viral predation and invading nucleic acids. While the mechanism of action for this acquired immunity is currently under investigation, the response of Cas protein expression to phage infection has yet to be elucidated. In this study, we employed shotgun proteomics to measure the global proteome expression in a model system for studying the CRISPR/Cas response in S. thermophilus DGCC7710 infected with phage 2972. Host and viral proteins were simultaneously measured following inoculation at two different multiplicities of infection and across various time points using two-dimensional liquid chromatography tandem mass spectrometry. Thirty-seven out of forty predicted viral proteins were detected, including all proteins of the structural virome and viral effector proteins. In total, 1,013 of 2,079 predicted S. thermophilus proteins were detected, facilitating the monitoring of host protein synthesis changes in response to virus infection. Importantly, Cas proteins from all four CRISPR loci in the S. thermophilus DGCC7710 genome were detected, including loci previously thought to be inactive. Many Cas proteins were found to be constitutively expressed, but several demonstrated increased abundance following infection, including the signature Cas9 proteins from the CRISPR1 and CRISPR3 loci, which are key players in the interference phase of the CRISPR/Cas response. Altogether, these results provide novel insights into the proteomic response of S. thermophilus, specifically CRISPR-associated proteins, upon phage 2972 infection