Indirect effects of the COVID-19 pandemic on paediatric healthcare use and severe disease: a retrospective national cohort study

OBJECTIVES: To determine the indirect consequences of the COVID-19 pandemic on paediatric healthcare utilisation and severe disease at a national level following lockdown on 23 March 2020. DESIGN: National retrospective cohort study. SETTING: Emergency childhood primary and secondary care providers across Scotland; two national paediatric intensive care units (PICUs); statutory death records. PARTICIPANTS: 273 455 unscheduled primary care attendances; 462 437 emergency department attendances; 54 076 emergency hospital admissions; 413 PICU unplanned emergency admissions requiring invasive mechanical ventilation; and 415 deaths during the lockdown study period and equivalent dates in previous years. MAIN OUTCOME MEASURES: Rates of emergency care consultations, attendances and admissions; clinical severity scores on presentation to PICU; rates and causes of childhood death. For all data sets, rates during the lockdown period were compared with mean or aggregated rates for the equivalent dates in 2016–2019. RESULTS: The rates of emergency presentations to primary and secondary care fell during lockdown in comparison to previous years. Emergency PICU admissions for children requiring invasive mechanical ventilation also fell as a proportion of cases for the entire population, with an OR of 0.52 for likelihood of admission during lockdown (95% CI 0.37 to 0.73), compared with the equivalent period in previous years. Clinical severity scores did not suggest children were presenting with more advanced disease. The greatest reduction in PICU admissions was for diseases of the respiratory system; those for injury, poisoning or other external causes were equivalent to previous years. Mortality during lockdown did not change significantly compared with 2016–2019. CONCLUSIONS: National lockdown led to a reduction in paediatric emergency care utilisation, without associated evidence of severe harm

Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution

Dietary protein dilution, where protein is reduced and replaced by other nutrient sources without caloric restriction, promotes metabolic health via the hepatokine Fgf21. Here, the authors show that essential amino acids threonine and tryptophan are necessary and sufficient to induce these effects

Time dependence of biomarkers:non-proportional effects of immunohistochemical panels predicting relapse risk in early breast cancer

Background:We investigated the impact of follow-up duration to determine whether two immunohistochemical prognostic panels, IHC4 and Mammostrat, provide information on the risk of early or late distant recurrence using the Edinburgh Breast Conservation Series and the Tamoxifen vs Exemestane Adjuvant Multinational (TEAM) trial.Methods:The multivariable fractional polynomial time (MFPT) algorithm was used to determine which variables had possible non-proportional effects. The performance of the scores was assessed at various lengths of follow-up and Cox regression modelling was performed over the intervals of 0-5 years and >5 years.Results:We observed a strong time dependence of both the IHC4 and Mammostrat scores, with their effects decreasing over time. In the first 5 years of follow-up only, the addition of both scores to clinical factors provided statistically significant information (P<0.05), with increases in R 2 between 5 and 6% and increases in D-statistic between 0.16 and 0.21.Conclusions:Our analyses confirm that the IHC4 and Mammostrat scores are strong prognostic factors for time to distant recurrence but this is restricted to the first 5 years after diagnosis. This provides evidence for their combined use to predict early recurrence events in order to select those patients who may/will benefit from adjuvant chemotherapy

A mouse model with a frameshift mutation in the nuclear factor I/X (NFIX) gene has phenotypic features of Marshall-Smith syndrome

The nuclear factor I/X (NFIX) gene encodes a ubiquitously expressed transcription factor whose mutations lead to two allelic disorders characterized by developmental, skeletal, and neural abnormalities, namely, Malan syndrome (MAL) and Marshall–Smith syndrome (MSS). NFIX mutations associated with MAL mainly cluster in exon 2 and are cleared by nonsense-mediated decay (NMD) leading to NFIX haploinsufficiency, whereas NFIX mutations associated with MSS are clustered in exons 6–10 and escape NMD and result in the production of dominant-negative mutant NFIX proteins. Thus, different NFIX mutations have distinct consequences on NFIX expression. To elucidate the in vivo effects of MSS-associated NFIX exon 7 mutations, we used CRISPR-Cas9 to generate mouse models with exon 7 deletions that comprised: a frameshift deletion of two nucleotides (Nfix Del2); in-frame deletion of 24 nucleotides (Nfix Del24); and deletion of 140 nucleotides (Nfix Del140). Nfix+/Del2, Nfix+/Del24, Nfix+/Del140, NfixDel24/Del24, and NfixDel140/Del140 mice were viable, normal, and fertile, with no skeletal abnormalities, but NfixDel2/Del2 mice had significantly reduced viability (p Nfix Del2 was not cleared by NMD, and NfixDel2/Del2 mice, when compared to Nfix+/+ and Nfix+/Del2 mice, had: growth retardation; short stature with kyphosis; reduced skull length; marked porosity of the vertebrae with decreased vertebral and femoral bone mineral content; and reduced caudal vertebrae height and femur length. Plasma biochemistry analysis revealed NfixDel2/Del2 mice to have increased total alkaline phosphatase activity but decreased C-terminal telopeptide and procollagen-type-1-N-terminal propeptide concentrations compared to Nfix+/+ and Nfix+/Del2 mice. NfixDel2/Del2 mice were also found to have enlarged cerebral cortices and ventricular areas but smaller dentate gyrus compared to Nfix+/+ mice. Thus, NfixDel2/Del2 mice provide a model for studying the in vivo effects of NFIX mutants that escape NMD and result in developmental abnormalities of the skeletal and neural tissues that are associated with MSS

Variation in postoperative outcomes of patients with intracranial tumors: insights from a prospective international cohort study during the COVID-19 pandemic

BACKGROUND: This study assessed the international variation in surgical neuro-oncology practice and 30-day outcomes of patients who had surgery for an intracranial tumor during the COVID-19 pandemic./ METHODS: We prospectively included adults aged ≥18 years who underwent surgery for a malignant or benign intracranial tumor across 55 international hospitals from 26 countries. Each participating hospital recorded cases for 3 consecutive months from the start of the pandemic. We categorized patients’ location by World Bank income groups (high [HIC], upper-middle [UMIC], and low- and lower-middle [LLMIC]). Main outcomes were a change from routine management, SARS-CoV-2 infection, and 30-day mortality. We used a Bayesian multilevel logistic regression stratified by hospitals and adjusted for key confounders to estimate the association between income groups and mortality./ RESULTS: Among 1016 patients, the number of patients in each income group was 765 (75.3%) in HIC, 142 (14.0%) in UMIC, and 109 (10.7%) in LLMIC. The management of 200 (19.8%) patients changed from usual care, most commonly delayed surgery. Within 30 days after surgery, 14 (1.4%) patients had a COVID-19 diagnosis and 39 (3.8%) patients died. In the multivariable model, LLMIC was associated with increased mortality (odds ratio 2.83, 95% credible interval 1.37–5.74) compared to HIC./ CONCLUSIONS: The first wave of the pandemic had a significant impact on surgical decision-making. While the incidence of SARS-CoV-2 infection within 30 days after surgery was low, there was a disparity in mortality between countries and this warrants further examination to identify any modifiable factors

Crop Updates 2000 - Weeds

This session covers thirty six papers from different authors: INTRODUCTION, Vanessa Stewart Agriculture Western Australia INTEGRATED WEED MANAGEMENT Effect of seeding density, row spacing and Trifluralin on the competitive ability of Annual Ryegrass in a minimum tillage system, David Minkey, Abul Hashem, Glen Riethmuller and Martin Harries, Agriculture Western Australia High wheat seeding rates coupled with narrow row spacing increases yield and suppresses grass, Peter Newman1 and Cameron Weeks2,1Agronomist, Elders Limited 2Mingenew/Irwin Group Resistant ryegrass management in a wheat – lupin rotation, Abul Hashem, Harmohinder S. Dhammu, Aik Cheam, David Bowran and Terry Piper, Agriculture Western Australia Integrated weed management – Will it work with my rotation? Alexandra Wallace, Agriculture Western Australia Long term herbicide resistance trial – Mingenew, Peter Newman Elders, Cameron Weeks Mingenew-Irwin Group Is two years enough? Bill Roy, Agricultural Consulting and Research Services The fate of ryegrass seed when sheep graze chaff cart heaps, Keith L. Devenish1 and Lisa J. Leaver2 1 Agriculture Western Australia, 2Curtin University of Technology, Muresk Institute of Agriculture Can blanket wiping and crop topping prevent seed set of resistant wild radish and mustard? StAbul Hashem, Harmohinder Dhammu, Vanessa Stewart, Brad Rayner and Mike Collins, Agriculture Western Australia The value of green manuring in the integrated management of ryegrass, Marta Monjardino1,2, David Pannell2, Stephen Powles1 ,1Western Australia Herbicide Resistance Initiative, 2Agricultural and Resource Economics, University of Western Australia Some ways of increasing wheat competitiveness against ryegrass,, Mike Collins Centre for Cropping Systems, Agriculture Western Australia WEED BIOLOGY Understanding and driving weed seed banks to very low levels, Sally Peltzer, Agriculture Western Australi HERBICIDE RESISTANCE Cross resistance of chlorsulfuron-resistant wild radish to imidazolinones, Abul Hashem, Harmohinder Dhammu and David Bowran, Agriculture Western Australia Investigation of suspected triazine resistant ryegrass populations for cross-resistance and multiple resistance to herbicides, Michael Walsh, Charles Boyle and Stephen Powles, Western Australian Herbicide Resistance Initiative, University of Western Australia Genetics and fitness of glyphosate resistant ryegrass, S. Powles1, P. Neve1, D. Lorraine-Colwill2, C. Preston2 ,1WAHRI, University of Western Australia 2 CRC Weed Management Systems, University of Adelaide Managing herbicide resistance – the effect of local extinction of resistance genes, Art Diggle1, Paul B. Neve2, Stephen B. Powles2 ,1Agriculture Western Australia, 2WAHRI, Faculty of Agriculture, University of Western Australia The double knock - the best strategy for conserving glyphosate susceptibility? Paul B. Neve1, Art Diggle2, Stephen B. Powles1,1WAHRI, Faculty of Agriculture, University of Western Australia, 2Agriculture Western Australia Wild radish had evolved resistance to triazines, Abul Hashem, Harmohinder S. Dhammu, David Bowran and Aik Cheam, Agriculture Western Australia Ryegrass resistance in Western Australia – where and how much? Rick Llewellyn and Stephen Powles, Western Australian Herbicide Resistance Initiative, Faculty of Agriculture, University of Western Australia Wild radish herbicide resistance survey, Michael Walsh, Ryan Duane and Stephen Powles, Western Australian Herbicide Resistance Initiative, University of Western Australia Knockdown resistance in the Western Australian wheatbelt – a proposed survey, Paul B. Neve1, Abul Hashem2, Stephen B. Powles1,1Western Australian Herbicide Resistance Initiative, University of Western Australia, 2Agriculture Western Australia Diflufenican resistant wild radish, Aik Cheam, Siew Lee, David Bowran, David Nicholson and Abul Hashem, Agriculture Western Australi Multiple resistance to triazines and diflufenican further complicates wild radish control, Aik Cheam, Siew Lee, David Bowran, David Nicholson and Abul Hashem, Agriculture Western Australia HERBICIDE TOLERANCE 25. Herbicide tolerance of lupins, Terry Piper, Weed Science Group, Agriculture Western Australia 26. Tanjil lupins will tolerate metribuzin under the right conditions, Peter Newman, Agronomist Elders Limited and Cameron Weeks, Mingenew/Irwin Group 27. Herbicide damage does not mean lower yield in Lupins, Peter Carlton, Trials Coordinator, Elders Limited 28. Herbicide tolerance of new pea varieties, Dr Terry Piper, Agriculture Western Australia 29. Herbicide tolerance of (waterlogged) wheat, Dr Terry Piper, Agriculture Western Australia 30. Wheat tolerance trials – Mingenew 1999, Peter Newman1, Cameron Weeks2 and Stewart Smith3,1Elders, Mingenew, 2Mingenew-Irwin Group,3Agriculture Western Australia ISSUES OF TRIFLURALIN USE 31. Trifluralin works better on ryegrass when no-tilling into thick wheat stubbles as granules, or mixed with limesand, Bill Crabtree, WANTFA Scientific Officer 32. Increasing trifluralin rate did not compensate for delaying incorporation, Bill Crabtree, WANTFA Scientific Officer 33. Poor emergence survey, 1999, Terry Piper, Weed Science Group, Agriculture Western Australia HERBICIDES – ISSUES AND OPTIONS 34. AFFINITY 400DF – A new herbicide with a new mode of action (Group G) for Broadleaf Weed Control in Cereals, Gordon Cumming, Technical Officer, Crop Care Australasia 35 Herbicide screening for Marshmallow, David Minkey1 and David Cameron2,1Agriculture Western Australia, 2Elders Ltd, Merredin 36. The control of Capeweed in Clearfield Production System for Canola, Mike Jackson and Scott Paton, Cyanamid Agriculture Pty Ltd 37.Effect of herbicides Tordonä 75D and Lontrelä,used for eradication of Skeleton Weed, on production of Lupins I the following seasons, John R. Peirce and Brad J. Rayner, Agriculture Western Australia INDUSTRY PROTECTION 38. Graingaurd – Opportunities for agribusiness to help protect the West Australian grains industry, Greg Shea, Executive Officer, GrainGuard Agriculture Western Australi

Whole genome scan reveals the genetic signature of African Ankole cattle breed and potential for higher quality beef

BACKGROUND: Africa is home to numerous cattle breeds whose diversity has been shaped by subtle combinations of human and natural selection. African Sanga cattle are an intermediate type of cattle resulting from interbreeding between Bos taurus and Bos indicus subspecies. Recently, research has asserted the potential of Sanga breeds for commercial beef production with better meat quality as compared to Bos indicus breeds. Here, we identified meat quality related gene regions that are positively selected in Ankole (Sanga) cattle breeds as compared to indicus (Boran, Ogaden, and Kenana) breeds using cross-population (XP-EHH and XP-CLR) statistical methods. RESULTS: We identified 238 (XP-EHH) and 213 (XP-CLR) positively selected genes, of which 97 were detected from both statistics. Among the genes obtained, we primarily reported those involved in different biological process and pathways associated with meat quality traits. Genes (CAPZB, COL9A2, PDGFRA, MAP3K5, ZNF410, and PKM2) involved in muscle structure and metabolism affect meat tenderness. Genes (PLA2G2A, PARK2, ZNF410, MAP2K3, PLCD3, PLCD1, and ROCK1) related to intramuscular fat (IMF) are involved in adipose metabolism and adipogenesis. MB and SLC48A1 affect meat color. In addition, we identified genes (TIMP2, PKM2, PRKG1, MAP3K5, and ATP8A1) related to feeding efficiency. Among the enriched Gene Ontology Biological Process (GO BP) terms, actin cytoskeleton organization, actin filament-based process, and protein ubiquitination are associated with meat tenderness whereas cellular component organization, negative regulation of actin filament depolymerization and negative regulation of protein complex disassembly are involved in adipocyte regulation. The MAPK pathway is responsible for cell proliferation and plays an important role in hyperplastic growth, which has a positive effect on meat tenderness. CONCLUSION: Results revealed several candidate genes positively selected in Ankole cattle in relation to meat quality characteristics. The genes identified are involved in muscle structure and metabolism, and adipose metabolism and adipogenesis. These genes help in the understanding of the biological mechanisms controlling beef quality characteristics in African Ankole cattle. These results provide a basis for further research on the genomic characteristics of Ankole and other Sanga cattle breeds for quality beef. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12863-016-0467-1) contains supplementary material, which is available to authorized users