Model evaluation in relation to soil N2O emissions: An algorithmic method which accounts for variability in measurements and possible time lags

AbstractThe loss of nitrogen from fertilised soils in the form of nitrous oxide (N2O) is a side effect of modern agriculture and the focus of many model-based studies. Due to the spatial and temporal heterogeneity of soil N2O emissions, the measured data can introduce limitations to the use of those statistical methods that are most commonly employed in the evaluation of model performance. In this paper, we describe these limitations and present an algorithm developed to address them. We implement the algorithm using simulated and measured N2O data from two UK arable sites. We show that possible time lags between the measured and simulated data can affect model evaluation and that their consideration in the evaluation process can reduce measures such as the Mean Squared Error (MSE) by 30%. We also analyse the algorithm's results to identify patterns in the estimated lags and to narrow down their possible causes

Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight

Lung adenocarcinoma promotion by air pollutants

A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development1. Here we propose that environmental particulate matter measuring ≤2.5 μm (PM2.5), known to be associated with lung cancer risk, promotes lung cancer by acting on cells that harbour pre-existing oncogenic mutations in healthy lung tissue. Focusing on EGFR-driven lung cancer, which is more common in never-smokers or light smokers, we found a significant association between PM2.5 levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in four within-country cohorts. Functional mouse models revealed that air pollutants cause an influx of macrophages into the lung and release of interleukin-1β. This process results in a progenitor-like cell state within EGFR mutant lung alveolar type II epithelial cells that fuels tumorigenesis. Ultradeep mutational profiling of histologically normal lung tissue from 295 individuals across 3 clinical cohorts revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively. These findings collectively support a tumour-promoting role for PM2.5 air pollutants and provide impetus for public health policy initiatives to address air pollution to reduce disease burden

Student teachers' views of pupil misbehaviour in classrooms: A Norwegian and an English setting compared

This paper examines how student teachers in Norway and England perceive pupil misbehaviour. The data are based on an opportunistic questionnaire survey of 86 student teachers in Kristiansand and 100 student teachers in York. Student teachers' perceptions of the seriousness of infractions were significantly different with regard to 7 of the items, with the students in Norway being relatively more tolerant. There were a few differences linked to sex and age. A principal components analysis identified 6 factors that were labelled: aggression towards other pupils, delinquent behaviour, oppositional behaviour, passive deviance, anti-social behaviour, and off-task behaviour. With few exceptions, student teachers in Norway and England regarded serious aggressive, delinquent and anti-social behaviour as totally unacceptable. This suggests that it is appropriate to encourage student teachers (and their school mentors) to consistently censure these kinds of pupil misbehaviour

Aminoglycoside-induced mutation suppression (stop codon readthrough) as a therapeutic strategy for Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is the most common, lethal, X-linked genetic disease, affecting 1 in 3500 newborn males. It is caused by mutations in the DMD gene. Owing to the large size of the gene, the mutation rate in both germline and somatic cells is very high. Nearly 13–15% of DMD cases are caused by nonsense mutations leading to premature termination codons in the reading frame that results in truncated dystrophin protein. Currently there is no cure for DMD. The only available treatment is the use of glucocorticoids that have modest beneficial effects accompanied by significant side effects. Different therapeutic strategies have been developed ranging from gene therapy to exon skipping and nonsense mutation suppression to produce the full-length protein. These strategies have shown promise in the mdx mouse model of muscular dystrophy where they have been reported to ameliorate the dystrophic phenotype and correct the physiological defects in the membrane. Each of these molecular approaches are being investigated in clinical trials. Here we review nonsense mutation suppression by aminoglycosides as a therapeutic strategy to treat DMD with special emphasis on gentamicin-induced readthrough of disease-causing premature termination codons