The Use of Psychotropic Medication in Iranian Children with Developmental Disabilities

The use of psychotropic medication in children is increasing worldwide. Children with developmental disabilities seem to be prescribed these medications at a higher rate compared to their non-disabled peers. Little is known about prescribing in non-Western, middle-income studies. In Iran, the file records of 1133 children, aged 2 to 17 years, assessed as having autism spectrum disorder (ASD) or an intellectual disability (ID) in Tehran City and Province from 2005 to 2019 were collated, and information from parental reports of medications was extracted. Upwards of 80% of children with ASD and 56% of those with ID were prescribed a psychotropic medication with around one quarter in each group taking two or more medications. The rates were higher among male children showing difficult-to-manage behaviors such as hyperactivity, but less so for children of fathers with higher levels of education. The lack of alternative management strategies may be a significant driver for the use of psychotropic medications in Iran and other Low and Middle Income countries, despite their known side effects, and their failure to address the developmental needs of the children. Rather, multi-disciplinary, behavioral, therapeutic, and educational interventions are required, but these are not available widely in Iran, although a start has been made

Long-term tillage and crop rotation effect on soil aggregation

Non-Peer ReviewedTillage and cropping sequences play a key role in controlling soil aggregation. We measured water-stable aggregate (WSA), wind erodible fraction (WEF), and geometric mean diameter (GMD) for six mid to longterm (8 to 25 years) experiments comparing tillage and cropping sequences in the Brown, Dark Brown, and Black Chernozemic soils of Saskatchewan. In the coarse-textured soil, no-tillage (NT) had a higher value of WSA by 49% more than in the wheat-phase of fallow-wheat (F-W), and had a lower value of WEF by 27% less than in the fallow-phase of F-W compared with minimum tillage (MT). In the medium-textured soils, NT had a higher WAS, ranged from 17 to 38%, and a lower WEF, ranged from 37 to 64% compared with conventional tillage (CT), depending on crop rotation systems. The reduced WEF under NT in the medium-textured soils was due mainly to increased GMD. In the fine-textured soils, NT had a higher WSA, ranged from 10 to 19% compared with MT or CT, and a lower WEF by 47% compared with MT only in the heavy clay soil. Change in GMD was not detectable in the light- and fine-textured soils. Continuous cropping compared with rotations containing fallow improved soil physical properties by increasing WSA, reducing WEF in the medium and fine-textured soils, and increasing GMD only in the medium-textured soils. Of the three soil physical properties determined in this study, WSA was the most sensitive to changes in tillage and crop rotations, then WEF and the least GMD

Impact of crop management systems on Fusarium populations in spring wheat and barley on the Canadian prairies

Non-Peer Reviewe

Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer

We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival “neuronal” subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, long non-coding RNA (lncRNA), and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma in situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments. A multiplatform analysis of 412 muscle-invasive bladder cancer patients provides insights into mutational profiles with prognostic value and establishes a framework associating distinct tumor subtypes with clinical options

Alternate crops in dry environments

Non-Peer Reviewe

Crop rotation and tillage impact on carbon sequestration in Saskatchewan soils

Non-Peer ReviewedSix field experiments from the Brown to Black soil zones and from light- to heavy-textured soils in Saskatchewan were conducted to quantify C sequestration under different tillage and crop rotations. Continuous cropping compared with crop rotations containing various frequency of fallow sequestered soil C ranging from 0.5 to 6.7 Mg C ha-1, depending on the duration of experiments, frequency of fallow and soil texture. This increase in soil organic C under continuous cropping varied from 36 to 453 kg C ha-1yr-1. The potential for sequestering soil C with continuous cropping was greater in the Dark Brown and Black soil zones than in the Brown soil zone even through the frequency of fallow was greater in the Brown soil zone. No-tillage compared with conventional tillage also sequestered soil C ranging from 0.6 to 13.2 Mg C ha-1. This increase in soil organic C under notill varied from 50 to 528 kg C ha-1yr-1. With elimination of both tillage and fallow, the soil organic C increase was approximately 200 kg C ha-1yr-1 in the Brown soil zone regardless of soil texture, and from 600 to 800 kg C ha-1yr-1 in the Dark Brown and Black soil zones. Relative annual increase in soil organic C under no-till was approximately a linear function of clay content. This study also indicated that potential gains of soil organic C under no-till were not necessarily related to the level of soil organic C prior to adoption of no-till. Heavy-textured soils would have a greater potential for gains in soil organic C under no-till in the prairie soils

PPM1D truncating mutations confer resistance to chemotherapy and sensitivity to PPM1D inhibition in hematopoietic cells

Truncating mutations in the terminal exon of PPM1D have been identified in clonal hematopoiesis and myeloid neoplasms, with a striking enrichment in patients previously exposed to chemotherapy. In this study, we demonstrate that truncating PPM1D mutations confer a chemoresistance phenotype, resulting in the selective expansion of PPM1D-mutant hematopoietic cells in the presence of chemotherapy in vitro and in vivo. CRISPR-Cas9 mutational profiling of PPM1D in the presence of chemotherapy selected for the same exon 6 mutations identified in patient samples. These exon 6 mutations encode for a truncated protein that displays elevated expression and activity due to loss of a C-terminal degradation domain. Global phosphoproteomic profiling revealed altered phosphorylation of target proteins in the presence of the mutation, highlighting multiple pathways including the DNA damage response (DDR). In the presence of chemotherapy, PPM1D-mutant cells have an abrogated DDR resulting in altered cell cycle progression, decreased apoptosis, and reduced mitochondrial priming. We demonstrate that treatment with an allosteric, small molecule inhibitor of PPM1D reverts the phosphoproteomic, DDR, apoptotic, and mitochondrial priming changes observed in PPM1D-mutant cells. Finally, we show that the inhibitor preferentially kills PPM1D-mutant cells, sensitizes the cells to chemotherapy, and reverses the chemoresistance phenotype. These results provide an explanation for the enrichment of truncating PPM1D mutations in the blood of patients exposed to chemotherapy and in therapy-related myeloid neoplasms, and demonstrate that PPM1D can be a targeted in the prevention of clonal expansion of PPM1D-mutant cells and the treatment of PPM1D-mutant disease