Mathematical modelling of antimicrobial resistance in agricultural waste highlights importance of gene transfer rate

Antimicrobial resistance is of global concern. Most antimicrobial use is in agriculture; manures and slurry are especially important because they contain a mix of bacteria, including potential pathogens, antimicrobial resistance genes and antimicrobials. In many countries, manures and slurry are stored, especially over winter, before spreading onto fields as organic fertilizer. Thus these are a potential location for gene exchange and selection for resistance. We develop and analyze a mathematical model to quantify the spread of antimicrobial resistance in stored agricultural waste. We use parameters from a slurry tank on a UK dairy farm as an exemplar. We show that the spread of resistance depends in a subtle way on the rates of gene transfer and antibiotic inflow. If the gene transfer rate is high, then its reduction controls resistance, while cutting antibiotic inflow has little impact. If the gene transfer rate is low, then reducing antibiotic inflow controls resistance. Reducing length of storage can also control spread of resistance. Bacterial growth rate, fitness costs of carrying antimicrobial resistance and proportion of resistant bacteria in animal faeces have little impact on spread of resistance. Therefore effective treatment strategies depend critically on knowledge of gene transfer rates

EFFECT OF HABITAT AND FORAGING HEIGHT ON BAT ACTIVITY IN THE COASTAL PLAIN OF SOUTH CAROLINA

Double-crested cormorant (Phalacrocorax auritus) populations on the Great Lakes expanded greatly during the past 2 decades. On Lake Erie, the number of breeding cormorants increased from 174 birds (87 nests) in 1979 to 26,542 (13,271 nests) in 2000. In 2000, 81% of the breeding population was on 2 western-basin islands (East Sister and Middle Islands). The plant communities on these islands represent some of the last remnants of Carolinian vegetation in Canada. Our study is the first to quantitatively assess the relationship between the distribution of nesting cormorants and forest health. On East Sister Island, 2 measures of forest cover were obtained using infrared aerial photographs and ground-based measurements of leaf area index. These measures of forest cover were correlated (rs = 0.70, P < 0.001), which validated the use of remotely sensed data to assess forest cover. Cormorant nest density was negatively correlated with tree cover on both East Sister and Middle Islands. Temporal comparisons of Middle Island data indicated a reduction in tree cover from 1995 to 2001, and these reductions coincided with a large increase in the island's cormorant population. Although correlational in nature, our results suggest that cormorants may be detrimentally affecting island forests

Functional and phenotypical comparison of myofibroblasts derived from biopsies and bronchoalveolar lavage in mild asthma and scleroderma

BACKGROUND: Activated fibroblasts, which have previously been obtained from bronchoalveolar lavage fluid (BALF), are proposed to be important cells in the fibrotic processes of asthma and scleroderma (SSc). We have studied the motility for BALF derived fibroblasts in patients with SSc that may explain the presence of these cells in the airway lumen. Furthermore, we have compared phenotypic alterations in activated fibroblasts from BALF and bronchial biopsies from patients with mild asthma and SSc that may account for the distinct fibrotic responses. METHODS: Fibroblasts were cultured from BALF and bronchial biopsies from patients with mild asthma and SSc. The motility was studied using a cell migration assay. Western Blotting was used to study the expression of alpha-smooth muscle actin (α-SMA), ED-A fibronectin, and serine arginine splicing factor 20 (SRp20). The protein expression pattern was analyzed to reveal potential biomarkers using two-dimensional electrophoresis (2-DE) and sequencing dual matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-TOF). The Mann-Whitney method was used to calculate statistical significance. RESULTS: Increased migration and levels of ED-A fibronectin were observed in BALF fibroblasts from both groups of patients, supported by increased expression of RhoA, Rac1, and the splicing factor SRp20. However, these observations were exclusively accompanied by increased expression of α-SMA in patients with mild asthma. Compared to BALF fibroblasts in mild asthma, fibroblasts in SSc displayed a differential protein expression pattern of cytoskeletal- and scavenger proteins. These identified proteins facilitate cell migration, oxidative stress, and the excessive deposition of extracellular matrix observed in patients with SSc. CONCLUSION: This study demonstrates a possible origin for fibroblasts in the airway lumen in patients with SSc and important differences between fibroblast phenotypes in mild asthma and SSc. The findings may explain the distinct fibrotic processes and highlight the motile BALF fibroblast as a potential target cell in these disorders

The mesencephalic root of the fifth nerve. A comparative anatomical study

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49899/1/900460202_ftp.pd

A pre-Caloris synchronous rotation for Mercury

The planet Mercury is locked in a spin-orbit resonance where it rotates three times about its spin axis for every two orbits about the Sun. The current explanation for this unique state assumes that the initial rotation of this planet was prograde and rapid, and that tidal torques decelerated the planetary spin to this resonance. When core-mantle boundary friction is accounted for, capture into the 3/2 resonance occurs with a 26% probability, but the most probable outcome is capture into one of the higher-order resonances. Here we show that if the initial rotation of Mercury were retrograde, this planet would be captured into synchronous rotation with a 68% probability. Strong spatial variations of the impact cratering rate would have existed at this time, and these are shown to be consistent with the distribution of pre-Calorian impact basins observed by Mariner 10 and MESSENGER. Escape from this highly stable resonance is made possible by the momentum imparted by large basin-forming impact events, and capture into the 3/2 resonance occurs subsequently under favourable conditions.Comment: Nature Geosci., 201

Social Class

Discussion of class structure in fifth-century Athens, historical constitution of theater audiences, and the changes in the comic representation of class antagonism from Aristophanes to Menander

Evaluation of unclassified variants in the breast cancer susceptibility genes BRCA1 and BRCA2 using five methods: results from a population-based study of young breast cancer patients

Introduction Efforts are ongoing to determine the significance of unclassified variants (UVs) in the breast cancer susceptibility genes BRCA1/BRCA2, but no study has systematically assessed whether women carrying the suspected deleterious UVs have characteristics commonly seen among women carrying known deleterious or disease-causing mutations in BRCA1/BRCA2. Methods We sequenced BRCA1/BRCA2 in 1,469 population-based female breast cancer patients diagnosed between the ages of 20 and 49 years. We used existing literature to classify variants into known deleterious mutations, polymorphic variants, and UVs. The UVs were further classified as high risk or low risk based on five methods: allele frequency, Polyphen algorithm, sequence conservation, Grantham matrix scores, and a combination of the Grantham matrix score and sequence conservation. Furthermore, we examined whether patients who carry the variants classified as high risk using these methods have risk characteristics similar to patients with known deleterious BRCA1/BRCA2 mutations (early age at diagnosis, family history of breast cancer or ovarian cancer, and negative estrogen receptor/progesterone receptor). Results We identified 262 distinct BRCA1/BRCA2 variants, including 147 UVs, in our study population. The BRCA1 UV carriers, but not the BRCA2 UV carriers, who were classified as high risk using each classification method were more similar to the deleterious mutation carriers with respect to family history than those carriers classified as low risk. For example, the odds ratio of having a first-degree family history for the high-risk women classified using Polyphen was 3.39 (95% confidence interval = 1.16 to 9.94) compared with normal/polymorphic BRCA1 carriers. The corresponding odds ratio of low-risk women was 1.53 (95% confidence interval = 1.07 to 2.18). The odds ratio for high-risk women defined by allele frequency was 2.00 (95% confidence interval = 1.14 to 3.51), and that of low-risk women was 1.30 (95% confidence interval = 0.87 to 1.93). Conclusion The results suggest that the five classification methods yielded similar results. Polyphen was particularly better at isolating BRCA1 UV carriers likely to have a family history of breast cancer or ovarian cancer, and may therefore help to classify BRCA1 UVs. Our study suggests that these methods may not be as successful in classifying BRCA2 UVs

Bristol Girls Dance Project: A cluster randomised controlled trial of an after-school dance programme to increase physical activity among 11- to 12-year-old girls

Background: Many children do not meet UK physical activity (PA) guidelines. Girls are less active than boys, and the age-related decline in activity is steeper for girls. Dance is the favourite form of PA among adolescent girls in the UK. Participation in after-school dance classes could significantly contribute to girls’ PA. Therefore, after-school dance may be effective for increasing PA levels.Objectives: To determine the effectiveness and cost effectiveness of a dance-based intervention to increase the objectively assessed mean weekday minutes of moderate- to vigorous-intensity physical activity (MVPA) of Year 7 girls (11- and 12-year olds) 1 year after baseline measurement.Design: Two-arm cluster randomised controlled trial and economic evaluation. Year 7 girls in participant schools received a ‘taster’ session and were invited to participate. Up to 33 girls per school were able to participate. Schools were randomly assigned (equal numbers) to intervention or control arms.Setting: A total of 18 mainstream secondary schools across greater Bristol.Participants: Year 7 girls in participating schools who could participate in physical education.Intervention: Nine intervention schools received an after-school dance intervention (40 × 75-minute sessions) underpinned by self-determination theory, which attempts to improve intrinsic motivation for being active, and delivered by external dance instructors. Control schools continued as normal.Main outcome measures: The main outcome was accelerometer-assessed mean minutes of MVPA at T2. Measures were assessed at baseline (T0), the end of the intervention (T1) and at T0 + 52 weeks (T2).Results: Baseline MVPA levels were high. A total of 508 girls were included in the primary analysis, which found no difference in weekday MVPA between trial arms. There was no effect on secondary accelerometer outcomes. Data were subjected to a per-protocol analysis and no effect was found. However, at T1, girls who attended dance classes had 4.61 minutes more of MVPA and 14.27 minutes more of light-intensity activity between 15.00 and 17.00 on the days on which they attended intervention sessions. The intervention was inexpensive at £73 per participant (£63 when excluding dance instructor travel) but was not cost-effective owing to the ineffectiveness of the intervention. The European Quality of Life-5 Dimensions Youth survey data were unresponsive to changes in the sample. The process evaluation reported that girls in attendance enjoyed the sessions, that exertion levels were low during sessions and that attendance was low and declined. Fidelity to the session-plan manual was low but theoretical fidelity (to self-determination theory) was good. Qualitative information provides information for improving future interventions.Conclusions: The intervention was enjoyed by participants. However, there was no difference in the MVPA levels (which were high at baseline) of girls allocated to receive dance compared with girls receiving the control. High baseline MVPA levels indicate that the study appealed to an already active cohort and, therefore, may not have targeted those most in need of an intervention. Dance is an enjoyable activity for adolescent girls and could be further trialled as a means by which to increase PA. Research might consider the impact of dividing the intervention period into smaller blocks