Nitrogen fixation from pasture legumes is a fundamental process that contributes to the profitability and sustainability of dryland agricultural systems. The aim of this research was to determine whether well-managed pastures, based on aerial-seeding pasture legumes, could partially or wholly meet the nitrogen (N) requirements of subsequent grain crops in an annual rotation. Fifteen experiments were conducted in Western Australia with wheat, barley or canola crops grown in a rotation that included the pasture legume species French serradella (Ornithopus sativus), biserrula (Biserrula pelecinus), bladder clover (Trifolium spumosum), annual medics (Medicago spp.) and the non-aerial seeded subterranean clover (Trifolium subterraneum). After the pasture phase, five rates of inorganic N fertilizer (Urea, applied at 0, 23, 46, 69 and 92 kg/ha) were applied to subsequent cereal and oil seed crops. The yields of wheat grown after serradella, biserrula and bladder clover, without the use of applied N fertilizer, were consistent with the target yields for growing conditions of the trials (2.3 to 5.4 t/ha). Crop yields after phases of these pasture legume species were similar or higher than those following subterranean clover or annual medics. The results of this study suggest a single season of a legume-dominant pasture may provide sufficient organic N in the soil to grow at least one crop, without the need for inorganic N fertilizer application. This has implications for reducing inorganic N requirements and the carbon footprint of cropping in dryland agricultural systems.

Post-operative oral feeding difficulties in neonates and infants with CHD is common. While pre-operative oral feeding may be normal, oral feeding challenges manifest in the post-operative period without a clearly defined aetiology. The objective of this scoping review was to examine post-operative oral feeding in full-term neonates and infants with a CHD. Electronic databases query (1 January 1975–31 May 2021), hand-search of the reference lists of included studies, contact with experts, and review of relevant conferences were performed to identify quantitative studies evaluating post-operative oral feeding in full-term neonates and infants with a CHD. Associations with additional quantitative variables in these studies were also examined. Twenty-five studies met inclusion criteria. Eighty per cent were cohort studies that utilised retrospective chart review from a single institution. The primary variable of interest in all studies was oral feeding status upon discharge from neonatal hospitalisation. The most common risk factors evaluated with poor feeding at time of discharge were birth weight (36% of included studies), gestational age (44%), duration of post-operative intubation (48%), cardiac diagnosis (40%), and presence of genetic syndrome or chromosomal anomaly (36%). The most common health-related outcomes evaluated were length of hospital stay (40%) and length of ICU stay (16%). Only the health-related outcomes of length of hospital stay and length of ICU stay were consistently significantly associated with poor post-operative oral feeding across studies in this review. A clear aetiology of poor post-operative oral feeding remains unknown.

Herbicides that inhibit very-long-chain fatty acids (VLCFAs) have been widely used for preemergence control of annual monocot and small-seeded dicot weed species, such as waterhemp, since their discovery in the 1950s. VLCFA-inhibiting herbicides are often applied in combination with active ingredients that possess residual activity on small-seeded broadleaf weeds, which can make their contribution to preemergence waterhemp control difficult to quantify. Bare-ground field experiments were designed to investigate the efficacy of eight VLCFA-inhibiting herbicides applied at their minimum and maximum labeled rates for control of Illinois waterhemp populations. Four different locations were selected, two of which contained previously characterized VLCFA inhibitor–resistant waterhemp populations in Champaign County (CHR) and McLean County (MCR). Two locations with VLCFA inhibitor–sensitive waterhemp populations included the University of Illinois South Farm in Urbana, IL, and the Orr Research Center in Perry, IL. Soils at the CHR, MCR, and Urbana locations contained greater than 3% organic matter, but less than 3% organic matter at Perry. Non-encapsulated acetochlor and alachlor controlled CHR and MCR waterhemp populations 28 d after treatment (DAT), whereas other VLCFA-inhibiting herbicides resulted in 61% and 76% control of the CHR and MCR populations, respectively. In contrast, all VLCFA-inhibiting herbicides resulted in 81% and 88% control of the Perry and Urbana waterhemp populations, respectively, 28 DAT. Waterhemp control decreased by 42 DAT, especially for the VLCFA inhibitor–resistant CHR and MCR populations. Overall, VLCFA-inhibiting herbicides remain effective for controlling sensitive waterhemp, but most are not effective for controlling VLCFA inhibitor–resistant waterhemp populations. Proper herbicide stewardship and integrated weed management practices should be implemented to maintain VLCFA-inhibiting herbicide efficacy for waterhemp management in the future.

The Trial Innovation Network has established an infrastructure for single IRB review in response to federal policies. The Network’s single IRB (sIRBs) have successfully supported over 70 multisite studies via more than 800 reliance arrangements. This has generated several lessons learned that can benefit the national clinical research enterprise, as we work to improve the conduct of clinical trials. These lessons include distinguishing the roles of the single IRB from institutional Human Research Protections programs, establishing a consistent sIRB review model, standardizing collection of local context and supplemental, study-specific information, and educating and empowering lead study teams to support their sites.

This study aimed to explore effects of adjunctive minocycline treatment on inflammatory and neurogenesis markers in major depressive disorder (MDD). Serum samples were collected from a randomised, placebo-controlled 12-week clinical trial of minocycline (200 mg/day, added to treatment as usual) for adults (n = 71) experiencing MDD to determine changes in interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP) and brain derived neurotrophic factor (BDNF). General Estimate Equation modelling explored moderation effects of baseline markers and exploratory analyses investigated associations between markers and clinical outcomes. There was no difference between adjunctive minocycline or placebo groups at baseline or week 12 in the levels of IL-6 (week 12; placebo 2.06 ± 1.35 pg/ml; minocycline 1.77 ± 0.79 pg/ml; p = 0.317), LBP (week 12; placebo 3.74 ± 0.95 µg/ml; minocycline 3.93 ± 1.33 µg/ml; p = 0.525) or BDNF (week 12; placebo 24.28 ± 6.69 ng/ml; minocycline 26.56 ± 5.45 ng/ml; p = 0.161). Higher IL-6 levels at baseline were a predictor of greater clinical improvement. Exploratory analyses suggested that the change in IL-6 levels were significantly associated with anxiety symptoms (HAMA; p = 0.021) and quality of life (Q-LES-Q-SF; p = 0.023) scale scores. No other clinical outcomes were shown to have this mediation effect, nor did the other markers (LBP or BDNF) moderate clinical outcomes. There were no overall changes in IL-6, LBP or BDNF following adjunctive minocycline treatment. Exploratory analyses suggest a potential role of IL-6 on mediating anxiety symptoms with MDD. Future trials may consider enrichment of recruitment by identifying several markers or a panel of factors to better represent an inflammatory phenotype in MDD with larger sample size.

Background: Children with pathogenic variations in SCN8A can present with early infantile epileptic encephalopathy-13, benign familial infantile seizures-5 or intellectual disability alone without epilepsy. In this case series, we discuss six children with variants in SCN8A managed at BC Children’s Hospital. Methods: We describe clinical and genetic results on six individuals with SCN8A variants identified via clinical or research next-generation sequencing. Functional consequences of two SCN8A variants were assessed using electrophysiological analyses in transfected cells. Results: Clinical findings ranged from normal development with well-controlled epilepsy to significant developmental delay with treatment-resistant epilepsy. Phenotypes and genotypes in our cohort are described in the table below. Functional analysis supported gain-of-function in P2 and loss-of-function in P4. Conclusions: Our cohort expands the clinical and genotypic spectrum of SCN8A-related disorders. We establish functional evidence for two missense variants in SCN8A, including LoF variant in a patient with intellectual disability, and autism spectrum disorder without seizures.

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Microscopic examination of blood smears remains the gold standard for laboratory inspection and diagnosis of malaria. Smear inspection is, however, time-consuming and dependent on trained microscopists with results varying in accuracy. We sought to develop an automated image analysis method to improve accuracy and standardization of smear inspection that retains capacity for expert confirmation and image archiving. Here, we present a machine learning method that achieves red blood cell (RBC) detection, differentiation between infected/uninfected cells, and parasite life stage categorization from unprocessed, heterogeneous smear images. Based on a pretrained Faster Region-Based Convolutional Neural Networks (R-CNN) model for RBC detection, our model performs accurately, with an average precision of 0.99 at an intersection-over-union threshold of 0.5. Application of a residual neural network-50 model to infected cells also performs accurately, with an area under the receiver operating characteristic curve of 0.98. Finally, combining our method with a regression model successfully recapitulates intraerythrocytic developmental cycle with accurate lifecycle stage categorization. Combined with a mobile-friendly web-based interface, called PlasmoCount, our method permits rapid navigation through and review of results for quality assurance. By standardizing assessment of Giemsa smears, our method markedly improves inspection reproducibility and presents a realistic route to both routine lab and future field-based automated malaria diagnosis.

Comparative transcriptomics can be used to translate an understanding of gene regulatory networks from model systems to less studied species. Here, we use RNA-Seq to determine and compare gene expression dynamics through the floral transition in the model species Arabidopsis thaliana and the closely related crop Brassica rapa. We find that different curve registration functions are required for different genes, indicating that there is no single common ‘developmental time’ between Arabidopsis and B. rapa. A detailed comparison between Arabidopsis and B. rapa and between two B. rapa accessions reveals different modes of regulation of the key floral integrator SOC1, and that the floral transition in the B. rapa accessions is triggered by different pathways. Our study adds to the mechanistic understanding of the regulatory network of flowering time in rapid cycling B. rapa and highlights the importance of registration methods for the comparison of developmental gene expression data.

The distribution of genetic diversity in invasive plant populations can have important management implications. Alligatorweed [Alternanthera philoxeroides (Mart.) Griseb.] was introduced into the United States around 1900 and has since spread throughout much of the southern United States and California. A successful biological control program was initiated in the late 1960s that reduced A. philoxeroides in the southern United States, although control has varied geographically. The degree to which variation among genotypes may be responsible for variation in control efficacy has not been well studied due to a lack of genetic data. We sampled 373 plants from 90 sites across the United States and genotyped all samples at three chloroplast regions to help inform future management efforts. Consistent with clonal spread, there was high differentiation between sites, yet we found six haplotypes and high haplotype diversity (mean h = 0.48) across states, suggesting this plant has been introduced multiple times. Two of the haplotypes correspond to previously described biotypes that differ in their susceptibility to herbicides and herbivory. The geographic distribution of the three common haplotypes varied by latitude and longitude, while the other haplotypes were widespread or localized to one or a few sites. All the haplotypes we screened are hexaploid (6n = 102), which may enhance biological control. Future studies can use these genetic data to determine whether genotypes differ in their invasiveness or respond differently to control measures. Some states, for instance, have mainly a single haplotype that may respond more uniformly to a single control strategy, whereas other states may require a variety of control strategies. These data will also provide the basis for identifying the source regions in South America, which may lead to the discovery of new biological control agents more closely matched to particular genotypes.

Dietary protein is a pre-requisite for the maintenance of skeletal muscle mass; stimulating increases in muscle protein synthesis (MPS), via essential amino acids (EAA), and attenuating muscle protein breakdown, via insulin. Muscles are receptive to the anabolic effects of dietary protein, and in particular the EAA leucine, for only a short period (i.e. about 2–3 h) in the rested state. Thereafter, MPS exhibits tachyphylaxis despite continued EAA availability and sustained mechanistic target of rapamycin complex 1 signalling. Other notable characteristics of this ‘muscle full’ phenomenon include: (i) it cannot be overcome by proximal intake of additional nutrient signals/substrates regulating MPS; meaning a refractory period exists before a next stimulation is possible, (ii) it is refractory to pharmacological/nutraceutical enhancement of muscle blood flow and thus is not induced by muscle hypo-perfusion, (iii) it manifests independently of whether protein intake occurs in a bolus or intermittent feeding pattern, and (iv) it does not appear to be dependent on protein dose per se. Instead, the main factor associated with altering muscle full is physical activity. For instance, when coupled to protein intake, resistance exercise delays the muscle full set-point to permit additional use of available EAA for MPS to promote muscle remodelling/growth. In contrast, ageing is associated with blunted MPS responses to protein/exercise (anabolic resistance), while physical inactivity (e.g. immobilisation) induces a premature muscle full, promoting muscle atrophy. It is crucial that in catabolic scenarios, anabolic strategies are sought to mitigate muscle decline. This review highlights regulatory protein turnover interactions by dietary protein, exercise, ageing and physical inactivity.