Atmospheric ammonia is a precursor for secondary particulate matter formation, which harms human health and contributes to acidification and eutrophication. Under the 2012 Gothenburg Protocol, 2005 ...emissions must be cut by 6% by 2020. In the UK, 83% of total emissions originate from agricultural practices such as fertilizer use and rearing of livestock, with emissions that are spatially extensive and variable in nature. Such fugitive emissions make resolving and tracking of individual site performance challenging. The Directional Passive Air quality Sampler (DPAS) was trialled at Whim Bog, an experimental site with a wind-controlled artificial release of ammonia, in combination with CEH-developed ammonia samplers. Whilst saturation issues were identified, two DPAS-MANDE (Mini Annular Denuder) systems, when deployed in parallel, displayed an average relative deviation of 15% (2–54%) across all 12 directions, with the directions exposed to the ammonia source showing ∼5% difference. The DPAS-MANDE has shown great potential for directional discrimination and can contribute to the understanding and management of fugitive ammonia sources from intensive agriculture sites.
•A Directional Passive Air Sampler (DPAS) is proposed for ambient ammonia monitoring.•The DPAS was tested in the field with a wind-dependent artificial release of ammonia.•The sampling of the DPAS-MANDE system showed distinct directional discrimination.•The MANDEs within the DPAS are subject to diffusional interference and can saturate.•The DPAS-MANDE system may be used to identify and target fugitive sources of ammonia.
In the United States, Puerto Ricans and Mexicans have the highest and lowest asthma prevalence, morbidity, and mortality, respectively. Ethnic-specific differences in the response to drug treatment ...may contribute to differences in disease outcomes. Genetic variants at the beta(2)-adrenergic receptor (beta(2)AR) may modify asthma severity and albuterol responsiveness. We tested the association of beta(2)AR genotypes with asthma severity and bronchodilator response to albuterol in Puerto Ricans and Mexicans with asthma.
We used both family-based and cross-sectional tests of association with 8 beta(2)AR single nucleotide polymorphisms in 684 Puerto Rican and Mexican families. Regression analyses were used to determine the interaction between genotype, asthma severity, and bronchodilator drug responsiveness.
Among Puerto Ricans with asthma, the arginine (Arg) 16 allele was associated with greater bronchodilator response using both family-based and cross-sectional tests (p = 0.00001-0.01). We found a strong interaction of baseline FEV(1) with the Arg16Glycine (Gly) polymorphism in predicting bronchodilator response. Among Puerto Ricans with asthma with baseline FEV(1) < 80% of predicted, but not in those with FEV(1) > 80%, there was a very strong association between the Arg16 genotype and greater bronchodilator responsiveness. No association was observed between Arg16Gly genotypes and drug responsiveness among Mexicans with asthma.
Ethnic-specific pharmacogenetic differences exist between Arg16Gly genotypes, asthma severity, and bronchodilator response in Puerto Ricans and Mexicans with asthma. These findings underscore the need for additional research on racial/ethnic differences in asthma morbidity and drug responsiveness.
Summary Background Interferon beta-1a and glatiramer acetate are commonly prescribed for relapsing-remitting multiple sclerosis (RRMS), but no published randomised trials have directly compared these ...two drugs. Our aim in the REGARD (REbif vs Glatiramer Acetate in Relapsing MS Disease) study was to compare interferon beta-1a with glatiramer acetate in patients with RRMS. Methods In this multicentre, randomised, comparative, parallel-group, open-label study, patients with RRMS diagnosed with the McDonald criteria who had had at least one relapse within the previous 12 months were randomised to receive 44 μg subcutaneous interferon beta-1a three times per week or 20 mg subcutaneous glatiramer acetate once per day for 96 weeks to assess the time to first relapse. A subpopulation of 460 patients (230 from each group) also had serial MRI scans to assess T2-weighted and gadolinium-enhancing lesion number and volume. Treatments were assigned by a computer-generated randomisation list that was stratified by centre. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00078338. Findings Between February and December, 2004, 764 patients were randomly assigned: 386 to interferon beta-1a and 378 to glatiramer acetate. After 96 weeks, there was no significant difference between groups in time to first relapse (hazard ratio 0·94, 95% CI 0·74 to 1·21; p=0·64). Relapse rates were lower than expected: 258 patients (126 in the interferon beta-1a group and 132 in the glatiramer acetate group) had one or more relapses (the expected number was 460). For secondary outcomes, there were no significant differences for the number and change in volume of T2 active lesions or for the change in the volume of gadolinium-enhancing lesions, although patients treated with interferon beta-1a had significantly fewer gadolinium-enhancing lesions (0·24 vs 0·41 lesions per patient per scan, 95% CI −0·4 to 0·1; p=0·0002). Safety and tolerability profiles were consistent with the known profiles for both compounds. The overall number and severity of adverse events were similar between the treatments and were not an important cause for discontinuation of the trial during the 96 weeks. Interpretation There was no significant difference between interferon beta-1a and glatiramer acetate in the primary outcome. The ability to predict clinical superiority on the basis of results from previous studies might be limited by a trial population with low disease activity, which is an important consideration for ongoing and future trials in patients with RRMS. Funding EMD Serono; Pfizer.
To describe visual acuity (VA) and inflammation following cataract surgery in eyes with noninfectious posterior uveitis (NIPU) that were being treated with a fluocinolone acetonide (FA) intravitreal ...implant compared with those that were not.
Post hoc, subgroup analysis of data from a 3-year, dose-masked, randomized, multicenter trial evaluating the FA implant for the treatment of NIPU.
The subset of eyes that underwent cataract surgery during the 3-year trial. Eyes were either implanted with a 0.59- or a 2.1-mg FA implant, or, in the case of affected fellow eyes, received standard-of-care local treatment.
VA, anterior and posterior chamber inflammation at 1 and 3 months after surgery, and rate of uveitis recurrence and serious postoperative ocular adverse events.
Of 278 patients enrolled in the main trial, 132/142 phakic implanted eyes and 39/186 phakic non-implanted eyes underwent cataract surgery. Mean improvement in VA was significantly greater in implanted than non-implanted eyes at 1 (P = 0.0047) and 3 months (P = 0.0015) postoperatively; significantly fewer anterior chamber cells were seen in implanted than non-implanted eyes at 1 (P = 0.0084) and 3 months (P = 0.0002). Severity of vitreous haze was less in implanted than non-implanted eyes at 3 months postoperatively (P = 0.0005). The postsurgical uveitis recurrence rate was lower in implanted than non-implanted eyes (26.5% vs 44.4%; P = 0.0433). Glaucoma was reported in 19.7% of implanted eyes and no non-implanted eyes (P = 0.0008) postoperatively.
In this post hoc subgroup analysis, eyes with NIPU treated with the FA intravitreal implant demonstrated better vision and less intraocular inflammation following cataract surgery than non-implanted eyes. Recurrent uveitic inflammation did not appear to be triggered by cataract surgery. Glaucoma occurred more frequently in implanted eyes.
Acute postoperative endophthalmitis (APE) is a serious, although infrequent, complication of eye surgery that can result in significant morbidity and costs. This review addresses APE risk factors, ...associated bacterial pathogens, antibiotic resistance, and prevention.
Transforming growth factors-beta (TGF-beta) are fibrogenic factors that have been strongly implicated in the development of diabetic nephropathy. Our aim was to use two animal models the ...streptozotocin (STZ)-induced diabetic rat and the genetically prone biobreeding (BB) rat to fully characterize the responses of the renal TGF-beta system in both short- and long-term diabetes. In this study changes in the entire renal TGF-beta system, at both protein and messenger RNA (mRNA) levels, have been characterized using the techniques of immunocytochemistry, Western blotting, and ribonuclease protection assay. We also used Western blotting of pro-collagen-I C-peptide to demonstrate that the rate of fibrogenesis was highest over the first 2 weeks of diabetes. TGF-beta1, TGF-beta2, and receptor mRNA and protein were detected in the control nondiabetic kidney. It was found that dramatic and dynamic changes occur in all parts of the renal TGF-beta axis in both models of experimental diabetes, but TGF-beta2 and TGF-betaRII proteins were the predominant responsive element, particularly during the acute phase of disease. For example, during the acute phase of disease (0-30 days), although renal TGF-beta1 mRNA levels were elevated, no increases in the corresponding protein were detected in the kidney. By contrast, in the absence of changes in TGF-beta2 mRNA levels, twice as much TGF-beta2 protein was measured in the kidney by day 30 of STZ-induced diabetes compared with day 0 controls analyzed by Western blotting (P < 0.05), and the protein was localized both to the nuclei and cytoplasm of glomerular cells, analyzed by immunocytochemistry. In addition, three times as much TGF-betaRII protein was found by day 90 of STZ-induced diabetes compared with day 0 controls, making this the most responsive receptor type. These results suggest that the entire TGF-beta axis has a role in the etiology of kidney fibrosis and could be manipulated therapeutically to preserve kidney function.
This SAR study has shown that the salicylanilide is the pharmacophore for inhibition of the bacterial two-component system. Hydrophobic substituents improve the potency of inhibitors in this series; ...however, hydrophobicity is not the sole determinant for inhibition; structural and electronic requirements also exist. Closantel (
1) was found to inhibit a two-component system and to have antibacterial activity against drug resistant
S. aureus and
E. faecium.
This SAR study has shown that the salicylanilide is the pharmacophore for inhibition of the bacterial two-component system. Hydrophobic substituents improve the potency of inhibitors in this series; however, structural and electronic requirements also exist. Closantel (
1) is a two-component system inhibitor (IC
50 = 3.8 μM) and has antibacterial activity against drug resistant
S. aureus and
E. faecium (MICs of 1–2 μg/mL).
We present new visible–infrared (V−J) observations of 17 Kuiper Belt objects, of which 14 were observed in the visible and infrared wavebands simultaneously to limit the effects of lightcurve ...variations. Combining these data with our previously published visible–infrared data provides a dataset of 29 objects, 25 of which offer simultaneous V−J colors. We examine the resulting dataset for evidence of relationships between physical properties and orbital characteristics. We find no evidence of a color–size relationship (as previously suspected), at least over the size range sampled. The dataset supports the trend, reported elsewhere, that there is a predominance of red material on the surfaces of objects having perihelia beyond 40 AU. Our data are also supportive, albeit weakly, of a reported correlation between inclination and color in the classical Kuiper Belt — although it is perhaps more correct to say that our data show that there appears to be a lack of low inclination blue objects. Our V−J colors appear broadly correlated with published optical colors, thus suggesting that the surfaces of Kuiper Belt objects are subject to a single reddening agent.
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