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Water repellency of agricultural crop residues may affect the hydrologic balance and increase runoff loss of pesticides by greater wash off from hydrophobic residue. We conducted a laboratory study to measure water repellency and hydrophobicity of 30 major agricultural crops (grass, legume, cereal, oilseed, pulse, and specialty crops). Crop samples were collected in southern Alberta, Canada in 2017 and 2018. Water repellency (WR) of oven‐dried (60°C) and ground (<2 mm) crop residues was measured using the water drop penetration time (WDPT) and molarity of ethanol (MED) tests. Hydrophobicity was evaluated using the ratio of hydrophobic CH– to hydrophilic CO–functional groups using Fourier Transform Infrared (FTIR) spectroscopy. The WDPTs of the 30 agricultural crops ranged from 8.3 to 2438 s, suggesting that crop species influenced WR of the dried and undecomposed residues. Needle‐and‐thread grass (Stipa comata Trin. and Rupr.), blue grama (Bouteloua gracilis [Kunth] Lag. ex Griffiths), and western wheatgrass (Agropyron smithii Rydb.) were the most WR crops based on WDPT. Fababean (Vicia faba), mustard (Sinapis alba L.), and sweet clover (Melilotus officinalis) were the least WR crops. Mean WDPTs were significantly (P ≤ 0.05) greater for grass than the other four crop types by 23 to 44 times. Significant differences in WDPT occurred among crop species within each of the six crop types. A significant positive correlation occurred between WDPT and hydrophobicity (r = 0.54), but not between WDPT and organic carbon. Overall, crop type and species may influence WR of crop residues and could affect the hydrologic balance. Core Ideas Agricultural crop species residue influenced water repellency and hydrophobicity Grass was the most water repellent and hydrophobic crop type A positive correlation occurred between water repellency and hydrophobicity The physical morphology of leaves may contribute to water repellency Water repellency differences also occurred for species within the six crop types

Molecular genetic analysis offers opportunities to advance our understanding of the nosological relationship between psychiatric diagnostic categories in general, and the mood and psychotic disorders in particular. Strong evidence ( P =7.0 × 10 −7 ) of association at the polymorphism rs1006737 (within CACNA1C, the gene encoding the α-1C subunit of the L-type voltage-gated calcium channel) with the risk of bipolar disorder (BD) has recently been reported in a meta-analysis of three genome-wide association studies of BD, including our BD sample ( N =1868) studied within the Wellcome Trust Case Control Consortium. Here, we have used our UK case samples of recurrent major depression ( N =1196) and schizophrenia ( N =479) and UK non-psychiatric comparison groups ( N =15316) to examine the spectrum of phenotypic effect of the bipolar risk allele at rs1006737. We found that the risk allele conferred increased risk for schizophrenia ( P =0.034) and recurrent major depression ( P =0.013) with similar effect sizes to those previously observed in BD (allelic odds ratio ∼1.15). Our findings are evidence of some degree of overlap in the biological underpinnings of susceptibility to mental illness across the clinical spectrum of mood and psychotic disorders, and show that at least some loci can have a relatively general effect on susceptibility to diagnostic categories, as currently defined. Our findings will contribute to a better understanding of the pathogenesis of major psychiatric illness, and such knowledge should be useful in providing an etiological rationale for shaping psychiatric nosology, which is currently reliant entirely on descriptive clinical data.

Two radiotherapy fractionation schedules are used to treat locally advanced bladder cancer: 64 Gy in 32 fractions over 6·5 weeks and a hypofractionated schedule of 55 Gy in 20 fractions over 4 weeks. Long-term outcomes of these schedules in several cohort studies and case series suggest that response, survival, and toxicity are similar, but no direct comparison has been published. The present study aimed to assess the non-inferiority of 55 Gy in 20 fractions to 64 Gy in 32 fractions in terms of invasive locoregional control and late toxicity in patients with locally advanced bladder cancer. We did a meta-analysis of individual patient data from patients (age ≥18 years) with locally advanced bladder cancer (T1G3 [high-grade non-muscle invasive] or T2–T4, N0M0) enrolled in two multicentre, randomised, controlled, phase 3 trials done in the UK: BC2001 (NCT00024349; assessing addition of chemotherapy to radiotherapy) and BCON (NCT00033436; assessing hypoxia-modifying therapy combined with radiotherapy). In each trial, the fractionation schedule was chosen according to local standard practice. Co-primary endpoints were invasive locoregional control (non-inferiority margin hazard ratio [HR]=1·25); and late bladder or rectum toxicity, assessed with the Late Effects Normal Tissue Task Force-Subjective, Objective, Management, Analytic tool (non-inferiority margin for absolute risk difference [RD]=10%). If non-inferiority was met for invasive locoregional control, superiority could be considered if the 95% CI for the treatment effect excluded the null effect (HR=1). One-stage individual patient data meta-analysis models for the time-to-event and binary outcomes were used, accounting for trial differences, within-centre correlation, randomised treatment received, baseline variable imbalances, and potential confounding from relevant prognostic factors. 782 patients with known fractionation schedules (456 from the BC2001 trial and 326 from the BCON trial; 376 (48%) received 64 Gy in 32 fractions and 406 (52%) received 55 Gy in 20 fractions) were included in our meta-analysis. Median follow-up was 120 months (IQR 99–159). Patients who received 55 Gy in 20 fractions had a lower risk of invasive locoregional recurrence than those who received 64 Gy in 32 fractions (adjusted HR 0·71 [95% CI 0·52–0·96]). Both schedules had similar toxicity profiles (adjusted RD −3·37% [95% CI −11·85 to 5·10]). A hypofractionated schedule of 55 Gy in 20 fractions is non-inferior to 64 Gy in 32 fractions with regard to both invasive locoregional control and toxicity, and is superior with regard to invasive locoregional control. 55 Gy in 20 fractions should be adopted as a standard of care for bladder preservation in patients with locally advanced bladder cancer. Cancer Research UK.

The Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC) highlighted 81 single-nucleotide polymorphisms (SNPs) with moderate evidence for association to schizophrenia. After follow-up in independent samples, seven loci attained genome-wide significance (GWS), but multi-locus tests suggested some SNPs that did not do so represented true associations. We tested 78 of the 81 SNPs in 2640 individuals with a clinical diagnosis of schizophrenia attending a clozapine clinic (CLOZUK), 2504 cases with a research diagnosis of bipolar disorder, and 2878 controls. In CLOZUK, we obtained significant replication to the PGC-associated allele for no fewer than 37 (47%) of the SNPs, including many prior GWS major histocompatibility complex (MHC) SNPs as well as 3/6 non-MHC SNPs for which we had data that were reported as GWS by the PGC. After combining the new schizophrenia data with those of the PGC, variants at three loci ( ITIH3/4 , CACNA1C and SDCCAG8 ) that had not previously been GWS in schizophrenia attained that level of support. In bipolar disorder, we also obtained significant evidence for association for 21% of the alleles that had been associated with schizophrenia in the PGC. Our study independently confirms association to three loci previously reported to be GWS in schizophrenia, and identifies the first GWS evidence in schizophrenia for a further three loci. Given the number of independent replications and the power of our sample, we estimate 98% (confidence interval (CI) 78–100%) of the original set of 78 SNPs represent true associations. We also provide strong evidence for overlap in genetic risk between schizophrenia and bipolar disorder.

The Pax3/7 transcription factor family is integral to developmental gene networks contributing to important innovations in vertebrate evolution, including the neural crest. The basal chordate lineage of amphioxus is ideally placed to understand the dynamics of the gene regulatory network evolution that produced these novelties. We report here the discovery that the cephalochordate lineage possesses two Pax3/7 genes, Pax3/7a and Pax3/7b . The tandem duplication is ancestral to all extant amphioxus, occurring in both Asymmetron and Branchiostoma , but originated after the split from the lineage leading to vertebrates. The two paralogues are differentially expressed during embryonic development, particularly in neural and somitic tissues, suggesting distinct regulation. Our results have implications for the study of amphioxus regeneration, neural plate and crest evolution, and differential tandem paralogue evolution.

Cochliomyia hominivorax and Lucilia cuprina are major pests of livestock. Their larvae infest warm-blooded vertebrates and feed on host’s tissues, resulting in severe industry losses. As they are serious pests, considerable effort has been made to develop genomic resources and functional tools aiming to improve their management and control. Here, we report a significant addition to the pool of genome manipulation tools through the establishment of efficient CRISPR/Cas9 protocols for the generation of directed and inheritable modifications in the genome of these flies. Site-directed mutations were introduced in the C. hominivorax and L. cuprina yellow genes (ChY and LcY) producing lightly pigmented adults. High rates of somatic mosaicism were induced when embryos were injected with Cas9 ribonucleoprotein complexes (RNPs) pre-assembled with guide RNAs (sgRNAs) at high concentrations. Adult flies carrying disrupted yellow alleles lacked normal pigmentation (brown body phenotype) and efficiently transmitted the mutated alleles to the subsequent generation, allowing the rapid creation of homozygous strains for reverse genetics of candidate loci. We next used our established CRISPR protocol to disrupt the C. hominivorax transformer gene (Chtra). Surviving females carrying mutations in the Chtra locus developed mosaic phenotypes of transformed ovipositors with characteristics of male genitalia while exhibiting abnormal reproductive tissues. The CRISPR protocol described here is a significant improvement on the existing toolkit of molecular methods in calliphorids. Our results also suggest that Cas9-based systems targeting Chtra and Lctra could be an effective means for controlling natural populations of these important pests.

The Caribbean reef shark (Carcharhinus perezi) is an economically important species in The Bahamas, where it is protected from fishing and is a mainstay for the shark dive tourism industry. Significant declines in abundance are suspected throughout much of its range, making the study of its life history and spatial ecology important for effective fisheries management and conservation planning. We used tag-recapture data collected in The Bahamas between 2008 and 2020 to investigate the species’ linear movements, population characteristics, life history, and growth. Sharks moved little between tag and recapture events (range: 0 to 8 km) despite multiple years at liberty for many sharks (range: 2 days to 7.1 years). We found no evidence of seasonal migration. We used a combined-sex von Bertalanffy growth function to estimate an asymptotic mean length at age (TL∞) of 205.8 cm total length and a growth coefficient (k) of 0.06. Theoretical maximum longevity was 43.3 to 57.8 years. Median male length at maturity (L50) was 148.9 cm total length (95% CI: 146.1–151.5 cm), which likely occurs around 14.8 years of age. Our results indicate slower growth of the Caribbean reef shark in The Bahamas than previously estimated in Venezuela. Our results suggest the Caribbean reef shark may be more vulnerable to overfishing and extirpation at the northern extent of its range than previously considered and that large no-take areas may be an effective conservation tool for this species.

Excitable optoelectronic devices represent one of the key building blocks for implementation of artificial spiking neurons in neuromorphic (brain-inspired) photonic systems. This work introduces and experimentally investigates an opto-electro-optical (O/E/O) artificial neuron built with a resonant tunnelling diode (RTD) coupled to a photodetector as a receiver and a vertical cavity surface emitting laser as a transmitter. We demonstrate a well-defined excitability threshold, above which the neuron produces optical spiking responses with characteristic neural-like refractory period. We utilise its fan-in capability to perform in-device coincidence detection (logical AND) and exclusive logical OR (XOR) tasks. These results provide first experimental validation of deterministic triggering and tasks in an RTD-based spiking optoelectronic neuron with both input and output optical (I/O) terminals. Furthermore, we also investigate in simulation the prospects of the proposed system for nanophotonic implementation in a monolithic design combining a nanoscale RTD element and a nanolaser; therefore demonstrating the potential of integrated RTD-based excitable nodes for low footprint, high-speed optoelectronic spiking neurons in future neuromorphic photonic hardware.

Background The INNODIA consortium has established a pan-European infrastructure using validated centres to prospectively evaluate clinical data from individuals with newly diagnosed type 1 diabetes combined with centralised collection of clinical samples to determine rates of decline in beta-cell function and identify novel biomarkers, which could be used for future stratification of phase 2 clinical trials. Methods In this context, we have developed a Master Protocol, based on the “backbone” of the INNODIA natural history study, which we believe could improve the delivery of phase 2 studies exploring the use of single or combinations of Investigational Medicinal Products (IMPs), designed to prevent or reverse declines in beta-cell function in individuals with newly diagnosed type 1 diabetes. Although many IMPs have demonstrated potential efficacy in phase 2 studies, few subsequent phase 3 studies have confirmed these benefits. Currently, phase 2 drug development for this indication is limited by poor evaluation of drug dosage and lack of mechanistic data to understand variable responses to the IMPs. Identification of biomarkers which might permit more robust stratification of participants at baseline has been slow. Discussion The Master Protocol provides (1) standardised assessment of efficacy and safety, (2) comparable collection of mechanistic data, (3) the opportunity to include adaptive designs and the use of shared control groups in the evaluation of combination therapies, and (4) benefits of greater understanding of endpoint variation to ensure more robust sample size calculations and future baseline stratification using existing and novel biomarkers.