Wet scavenging of soluble gases in DC3 deep convective storms using WRF-Chem simulations and aircraft observations

We examine wet scavenging of soluble trace gases in storms observed during the Deep Convective Clouds and Chemistry (DC3) field campaign. We conduct high-resolution simulations with the Weather Research and Forecasting model with Chemistry (WRF-Chem) of a severe storm in Oklahoma. The model represents well the storm location, size, and structure as compared with Next Generation Weather Radar reflectivity, and simulated CO transport is consistent with aircraft observations. Scavenging efficiencies (SEs) between inflow and outflow of soluble species are calculated from aircraft measurements and model simulations. Using a simple wet scavenging scheme, we simulate the SE of each soluble species within the error bars of the observations. The simulated SEs of all species except nitric acid (HNO_3) are highly sensitive to the values specified for the fractions retained in ice when cloud water freezes. To reproduce the observations, we must assume zero ice retention for formaldehyde (CH_2O) and hydrogen peroxide (H_2O_2) and complete retention for methyl hydrogen peroxide (CH_3OOH) and sulfur dioxide (SO_2), likely to compensate for the lack of aqueous chemistry in the model. We then compare scavenging efficiencies among storms that formed in Alabama and northeast Colorado and the Oklahoma storm. Significant differences in SEs are seen among storms and species. More scavenging of HNO_3 and less removal of CH_3OOH are seen in storms with higher maximum flash rates, an indication of more graupel mass. Graupel is associated with mixed-phase scavenging and lightning production of nitrogen oxides (NO_x), processes that may explain the observed differences in HNO_3 and CH_3OOH scavenging

Genome-wide association study identifies loci on 12q24 and 13q32 associated with Tetralogy of Fallot

We conducted a genome-wide association study to search for risk alleles associated with Tetralogy of Fallot (TOF), using a northern European discovery set of 835 cases and 5159 controls. A region on chromosome 12q24 was associated (P = 1.4 × 10−7) and replicated convincingly (P = 3.9 × 10−5) in 798 cases and 2931 controls [per allele odds ratio (OR) = 1.27 in replication cohort, P = 7.7 × 10−11 in combined populations]. Single nucleotide polymorphisms in the glypican 5 gene on chromosome 13q32 were also associated (P = 1.7 × 10−7) and replicated convincingly (P = 1.2 × 10−5) in 789 cases and 2927 controls (per allele OR = 1.31 in replication cohort, P = 3.03 × 10−11 in combined populations). Four additional regions on chromosomes 10, 15 and 16 showed suggestive association accompanied by nominal replication. This study, the first genome-wide association study of a congenital heart malformation phenotype, provides evidence that common genetic variation influences the risk of TO

Genome-wide association study identifies loci on 12q24 and 13q32 associated with tetralogy of Fallot

We conducted a genome-wide association study to search for risk alleles associated with Tetralogy of Fallot (TOF), using a northern European discovery set of 835 cases and 5159 controls. A region on chromosome 12q24 was associated (P = 1.4 × 10(-7)) and replicated convincingly (P = 3.9 × 10(-5)) in 798 cases and 2931 controls [per allele odds ratio (OR) = 1.27 in replication cohort, P = 7.7 × 10(-11) in combined populations]. Single nucleotide polymorphisms in the glypican 5 gene on chromosome 13q32 were also associated (P = 1.7 × 10(-7)) and replicated convincingly (P = 1.2 × 10(-5)) in 789 cases and 2927 controls (per allele OR = 1.31 in replication cohort, P = 3.03 × 10(-11) in combined populations). Four additional regions on chromosomes 10, 15 and 16 showed suggestive association accompanied by nominal replication. This study, the first genome-wide association study of a congenital heart malformation phenotype, provides evidence that common genetic variation influences the risk of TOF

Antibiotic residues in final effluents of European wastewater treatment plants and their impact on the aquatic environment

A comprehensive monitoring of a broad set of antibiotics in the final effluent of wastewater treatment plants (WWTPs) of 7 European countries (Portugal, Spain, Ireland, Cyprus, Germany, Finland, and Norway) was carried out in two consecutive years (2015 and 2016). This is the first study of this kind performed at an international level. Within the 53 antibiotics monitored 17 were detected at least once in the final effluent of the WWTPs, i.e.: ciprofloxacin, ofloxacin, enrofloxacin, orbifloxacin, azithromycin, clarithromycin, sulfapyridine, sulfamethoxazole, trimethoprim, nalidixic acid, pipemidic acid, oxolinic acid, cefalexin, clindamycin, metronidazole, ampicillin, and tetracycline. The countries exhibiting the highest effluent average concentrations of antibiotics were Ireland and the southern countries Portugal and Spain, whereas the northern countries (Norway, Finland and Germany) and Cyprus exhibited lower total concentration. The antibiotic occurrence data in the final effluents were used for the assessment of their impact on the aquatic environment. Both, environmental predicted no effect concentration (PNEC-ENVs) and the PNECs based on minimal inhibitory concentrations (PNEC-MICs) were considered for the evaluation of the impact on microbial communities in aquatic systems and on the evolution of antibiotic resistance, respectively. Based on this analysis, three compounds, ciprofloxacin, azithromycin and cefalexin are proposed as markers of antibiotic pollution, as they could occasionally pose a risk to the environment. Integrated studies like this are crucial to map the impact of antibiotic pollution and to provide the basis for designing water quality and environmental risk in regular water monitoring programs.Peer reviewe

Temporal changes in clinical and radiographic variables in dogs with preclinical myxomatous mitral valve disease: The EPIC study

The Evaluation of pimobendan in dogs with cardiomegaly caused by preclinical myxomatous mitral valve disease (EPIC) study monitored dogs with myxomatous mitral valve disease (MMVD) as they developed congestive heart failure (CHF)

The Highly Virulent 2006 Norwegian EHEC O103:H25 Outbreak Strain Is Related to the 2011 German O104:H4 Outbreak Strain

In 2006, a severe foodborne EHEC outbreak occured in Norway. Seventeen cases were recorded and the HUS frequency was 60%. The causative strain, Esherichia coli O103:H25, is considered to be particularly virulent. Sequencing of the outbreak strain revealed resemblance to the 2011 German outbreak strain E. coli O104:H4, both in genome and Shiga toxin 2-encoding (Stx2) phage sequence. The nucleotide identity between the Stx2 phages from the Norwegian and German outbreak strains was 90%. During the 2006 outbreak, stx2-positive O103:H25 E. coli was isolated from two patients. All the other outbreak associated isolates, including all food isolates, were stx-negative, and carried a different phage replacing the Stx2 phage. This phage was of similar size to the Stx2 phage, but had a distinctive early phage region and no stx gene. The sequence of the early region of this phage was not retrieved from the bacterial host genome, and the origin of the phage is unknown. The contaminated food most likely contained a mixture of E. coli O103:H25 cells with either one of the phages

Pre-Existing Isoniazid Resistance, but Not the Genotype of Mycobacterium Tuberculosis Drives Rifampicin Resistance Codon Preference in Vitro

Both the probability of a mutation occurring and the ability of the mutant to persist will influence the distribution of mutants that arise in a population. We studied the interaction of these factors for the in vitro selection of rifampicin (RIF)-resistant mutants of Mycobacterium tuberculosis. We characterised two series of spontaneous RIF-resistant in vitro mutants from isoniazid (INH)-sensitive and -resistant laboratory strains and clinical isolates, representing various M. tuberculosis genotypes. The first series were selected from multiple parallel 1 ml cultures and the second from single 10 ml cultures. RIF-resistant mutants were screened by Multiplex Ligation-dependent Probe Amplification (MLPA) or by sequencing the rpoB gene. For all strains the mutation rate for RIF resistance was determined with a fluctuation assay. The most striking observation was a shift towards rpoB-S531L (TCG→TTG) mutations in a panel of laboratory-generated INH-resistant mutants selected from the 10-ml cultures (p<0.001). All tested strains showed similar mutation rates (1.33×10−8 to 2.49×10−7) except one of the laboratory-generated INH mutants with a mutation rate measured at 5.71×10−7, more than 10 times higher than that of the INH susceptible parental strain (5.46–7.44×10−8). No significant, systematic difference in the spectrum of rpoB-mutations between strains of different genotypes was observed. The dramatic shift towards rpoB-S531L in our INH-resistant laboratory mutants suggests that the relative fitness of resistant mutants can dramatically impact the distribution of (subsequent) mutations that accumulate in a M. tuberculosis population, at least in vitro. We conclude that, against specific genetic backgrounds, certain resistance mutations are particularly likely to spread. Molecular screening for these (combinations of) mutations in clinical isolates could rapidly identify these particular pathogenic strains. We therefore recommend that isolates are screened for the distribution of resistance mutations, especially in regions that are highly endemic for (multi)drug resistant tuberculosis

The Chromatin Remodelling Complex B-WICH Changes the Chromatin Structure and Recruits Histone Acetyl-Transferases to Active rRNA Genes

The chromatin remodelling complex B-WICH, which comprises the William syndrome transcription factor (WSTF), SNF2h, and nuclear myosin 1 (NM1), is involved in regulating rDNA transcription, and SiRNA silencing of WSTF leads to a reduced level of 45S pre-rRNA. The mechanism behind the action of B-WICH is unclear. Here, we show that the B-WICH complex affects the chromatin structure and that silencing of the WSTF protein results in a compaction of the chromatin structure over a 200 basepair region at the rRNA promoter. WSTF knock down does not show an effect on the binding of the rRNA-specific enhancer and chromatin protein UBF, which contributes to the chromatin structure at active genes. Instead, WSTF knock down results in a reduced level of acetylated H3-Ac, in particular H3K9-Ac, at the promoter and along the gene. The association of the histone acetyl-transferases PCAF, p300 and GCN5 with the promoter is reduced in WSTF knock down cells, whereas the association of the histone acetyl-transferase MOF is retained. A low level of H3-Ac was also found in growing cells, but here histone acetyl-transferases were present at the rDNA promoter. We propose that the B-WICH complex remodels the chromatin structure at actively transcribed rRNA genes, and this allows for the association of specific histone acetyl-transferases

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

The impact of gender norms on condom use among HIV-positive adults in KwaZulu-Natal, South Africa.

Critical to preventing the spread of HIV is promoting condom use among HIV-positive individuals. Previous studies suggest that gender norms (social and cultural constructions of the ways that women and men are expected to behave) may be an important determinant of condom use. However, the relationship has not been evaluated among HIV-positive women and men in South Africa. We examined gender norms and condom use at last sex among 550 partnerships reported by 530 sexually-active HIV-positive women (372) and men (158) who had sought care, but not yet initiated antiretroviral therapy in a high HIV-prevalence rural setting in KwaZulu-Natal, South Africa between January 2009 and March 2011. Participants enrolled in the cohort study completed a baseline questionnaire that detailed their socio-demographic characteristics, socio-economic circumstances, religion, HIV testing history and disclosure of HIV status, stigma, social capital, gender norms and self-efficacy. Gender norms did not statistically differ between women and men (p = 0.18). Overall, condoms were used at last sex in 58% of partnerships. Although participants disclosed their HIV status in 66% of the partnerships, 60% did not have knowledge of their partner's HIV status. In multivariable logistic regression, run separately for each sex, women younger than 26 years with more equitable gender norms were significantly more likely to have used a condom at last sex than those of the same age group with inequitable gender norms (OR = 8.88, 95% CI 2.95-26.75); the association between condom use and gender norms among women aged 26+ years and men of all ages was not statistically significant. Strategies to address gender inequity should be integrated into positive prevention interventions, particularly for younger women, and supported by efforts at a societal level to decrease gender inequality