Revolutionary Self-Sustaining Pasture-Crop Rotation Systems Developed by Researcher-Farmer Collaboration for Southern Australian Farming Systems

Mixed farming pasture-crop rotation systems in southern Australia have traditionally relied on subterranean clover and annual medics. Concern over the long-term persistence of these species was raised in the 1980‟s with the cessation of manufacture of suction harvesters required for seed production. Subsequently, their adaptation has been tested due to climate change. More frequent droughts, particularly the millennium drought (2002-2009), increased incidence of false breaks and dry spring conditions causing decline or complete loss of seedbank reserves and failure of new sowings. A concerted effort developing new legume species for Australian farming systems, led by Western Australia, resulted in domestication of biserrula, bladder clover and gland clover and development of new cultivars of French and yellow serradella. These species/varieties possess characteristics including one or more of the following: higher hard seed content, deeper root systems, greater acid soil tolerance in symbiosis, increased herbage and seed production, wider tolerance to pest and diseases. They can also be harvested with conventional cereal harvesters reducing seed cost and enabling farmers to produce their own seed (Loi et al., 2005). A survey of farmers showed adoption of new species was limited by a lack of detailed management information on how to grow and manage them, to maximise their impact on crop and livestock productivity (Hackney et al., 2012). This paper reports on efforts made over a decade by a multidisciplinary WA and NSW team of plant breeders, rhizobiologists, agronomists and animal scientists, formed to develop new self-sustaining pasture-crop rotation systems to fill the void left by the failure of traditional rotation systems. The critical role and early recruitment of „champion‟ farmers in achieving the successful adoption of new technology is discussed, as is the difficulty in organizing and funding systems research

Comparison of the Lipidomic Signature of Fatty Liver in Children and Adults: A Cross-Sectional Study.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition in children characterised by insulin resistance and altered lipid metabolism. Affected patients are at increased risk of cardiovascular disease (CVD) and children with NAFLD are likely to be at risk of premature cardiac events. Evaluation of the plasma lipid profile of children with NAFLD offers the opportunity to investigate these perturbations and understand how closely they mimic the changes seen in adults with cardiometabolic disease. METHODS: We performed untargeted liquid chromatography-mass spectrometry (LC-MS) plasma lipidomics on 287 children: 19 lean controls, 146 from an obese cohort, and 122 NAFLD cases who had undergone liver biopsy. Associations between lipid species and liver histology were assessed using regression adjusted for age and sex. Results were then replicated using data from 9500 adults with metabolic phenotyping. RESULTS: More severe paediatric NAFLD was associated with lower levels of long chain, polyunsaturated phosphatidylcholines (pC) and triglycerides (TG). Similar trends in pC and TG chain length and saturation were seen in adults with hepatic steatosis; however, many of the specific lipids associated with NAFLD differed between children and adults. Five lipids replicated in adults (including PC(36:4)) have been directly linked to death and cardiometabolic disease, as well as indirectly via genetic variants. CONCLUSION: These findings suggest that, whilst similar pathways of lipid metabolism are perturbed in paediatric NAFLD as in cardiometabolic disease in adults, the specific lipid signature in children is different.JPM is supported by a Wellcome Trust fellowship (216329/Z/19/Z), a European Society for Paediatric Research (ESPR) Young Investigator Award, and a Children’s Liver Disease Foundation Grant. EU-PNAFLD Registry is supported by a European Association for Study of the Liver (EASL) Registry Grant. MZ is supported by a New Investigator Research Grant from the MRC (MR/T001917/1). BK is supported by grants from Van den Broek Lohman Foundation, Virtutis Opus Foundation and For Wishdom Foundation. SF, SGS & AK are supported by the BBSRC (BB/M027252/1 & BB/P028195/1), BJJ & AK are supported by the National Institute for Health Research (NIHR146281)

Perception of Sleep in Recovering Alcohol-Dependent Patients With Insomnia: Relationship With Future Drinking

Subjective and objective measures of poor sleep in alcoholic insomniacs predict relapse to drinking. Nonalcoholic insomniacs underestimate their total sleep time (TST) and overestimate their sleep onset latency (SOL) and wake time after sleep onset (WASO) compared with polysomnography (PSG). This study evaluated 3 hypotheses: (1) subjective SOL would predict frequency of future drinking; (2) participants would overestimate SOL and WASO and underestimate TST; and (3) higher amounts of over- and underestimates of sleep at baseline would predict worse drinking outcomes prospectively. Methods : Participants ( N =18), mean age 44.6 years (±13.2), underwent an adaptation night and then 2 nights of PSG 3 weeks apart. They also provided morning estimates of SOL, WASO, TST, and sleep efficiency (SE). Following the baseline PSG, participants were followed over 12 weeks. A 2-way ANOVA (night × method of measuring sleep) compared results and regression analyses predicted drinking. Drinking outcomes were defined as number of days drinking (DD) and number of heavy-drinking days (HDD) during 2 consecutive 6-week follow-up periods. Results : Most participants (72%) overestimated SOL by a mean of 21.3 (±36) minutes compared with PSG [ F (1, 14)=7.1, p <0.03]. Unexpectedly, 89% underestimated WASO by a mean difference of 48.7 (±49) minutes [ F (1, 14)=15.6, p <0.01]. Drinking during the first 6-week study period was predicted by both subjective estimates of WASO and their accuracy, whereas drinking during the second 6-week period was predicted by both subjective estimations of sleep and rapid eye movement sleep latency. Conclusion : Greater subjective accuracy of wakefulness at night provided by the patient predicted drinking during the study. Unlike nonalcoholic insomniacs, this alcoholic sample significantly underestimated WASO compared with PSG values. The predictive ability of sleep parameters depended on the selected measure of drinking outcomes and when outcomes were measured. Subjective sleep measures were better predictors of future drinking than corresponding PSG measures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65202/1/j.1530-0277.2006.00245.x.pd

Involvement in teaching improves learning in medical students: a randomized cross-over study

<p>Abstract</p> <p>Background</p> <p>Peer-assisted learning has many purported benefits including preparing students as educators, improving communication skills and reducing faculty teaching burden. But comparatively little is known about the effects of teaching on learning outcomes of peer educators in medical education.</p> <p>Methods</p> <p>One hundred and thirty-five first year medical students were randomly allocated to 11 small groups for the Gastroenterology/Hematology Course at the University of Calgary. For each of 22 sessions, two students were randomly selected from each group to be peer educators. Students were surveyed to estimate time spent preparing as peer educator versus group member. Students completed an end-of-course 94 question multiple choice exam. A paired t-test was used to compare performance on clinical presentations for which students were peer educators to those for which they were not.</p> <p>Results</p> <p>Preparation time increased from a mean (SD) of 36 (33) minutes baseline to 99 (60) minutes when peer educators (Cohen's <it>d </it>= 1.3; p < 0.001). The mean score (SD) for clinical presentations in which students were peer educators was 80.7% (11.8) compared to77.6% (6.9) for those which they were not (<it>d </it>= 0.33; <it>p </it>< 0.01).</p> <p>Conclusion</p> <p>Our results suggest that involvement in teaching small group sessions improves medical students' knowledge acquisition and retention.</p

Severe Plasmodium falciparum Malaria Is Associated with Circulating Ultra-Large von Willebrand Multimers and ADAMTS13 Inhibition

Plasmodium falciparum infection results in adhesion of infected erythrocytes to blood vessel endothelium, and acute endothelial cell activation, together with sequestration of platelets and leucocytes. We have previously shown that patients with severe infection or fulminant cerebral malaria have significantly increased circulatory levels of the adhesive glycoprotein von Willebrand factor (VWF) and its propeptide, both of which are indices of endothelial cell activation. In this prospective study of patients from Ghana with severe (n = 20) and cerebral (n = 13) P. falciparum malaria, we demonstrate that increased plasma VWF antigen (VWF∶Ag) level is associated with disproportionately increased VWF function. VWF collagen binding (VWF∶CB) was significantly increased in patients with cerebral malaria and severe malaria (medians 7.6 and 7.0 IU/ml versus 1.9 IU/ml; p<0.005). This increased VWF∶CB correlated with the presence of abnormal ultra-large VWF multimers in patient rather than control plasmas. Concomitant with the increase in VWF∶Ag and VWF∶CB was a significant persistent reduction in the activity of the VWF-specific cleaving protease ADAMTS13 (∼55% of normal; p<0.005). Mixing studies were performed using P. falciparum patient plasma and normal pooled plasma, in the presence or absence of exogenous recombinant ADAMTS13. These studies demonstrated that in malarial plasma, ADAMTS13 function was persistently inhibited in a time-dependent manner. Furthermore, this inhibitory effect was not associated with the presence of known inhibitors of ADAMTS13 enzymatic function (interleukin-6, free haemoglobin, factor VIII or thrombospondin-1). These novel findings suggest that severe P. falciparum infection is associated with acute endothelial cell activation, abnormal circulating ULVWF multimers, and a significant reduction in plasma ADAMTS13 function which is mediated at least in part by an unidentified inhibitor

Ash agglomeration and deposition during combustion of poultry litter in a bubbling fluidized-bed combustor

peer-reviewedn this study, we have characterized the ash resulting from fluidized bed combustion of poultry litter as being dominated by a coarse fraction of crystalline ash composed of alkali-Ca-phosphates and a fine fraction of particulate K2SO4 and KCl. Bed agglomeration was found to be coating-induced with two distinct layers present. The inner layer (0.05–0.09 mm thick) was formed due to the reaction of gaseous potassium with the sand (SiO2) surface forming K-silicates with low melting points. Further chemical reaction on the surface of the bed material strengthened the coating forming a molten glassy phase. The outer layer was composed of loosely bound, fine particulate ash originating from the char. Thermodynamic equilibrium calculations showed slag formation in the combustion zone is highly temperature-dependent, with slag formation predicted to increase from 1.8 kg at 600 °C to 7.35 kg at 1000 °C per hour of operation (5.21 kg of ash). Of this slag phase, SiO2 and K2O were the dominant phases, accounting for almost 95%, highlighting the role of K-silicates in initiating bed agglomeration. The remaining 5% was predicted to consist mainly of Al2O3, K2SO4, and Na2O. Deposition downstream in the low-temperature regions was found to occur mostly through the vaporization–condensation mechanism, with equilibrium decreasing significantly with decreasing temperatures. The dominant alkali chloride-containing gas predicted to form in the combustion zone was KCl, which corresponds with the high KCl content in the fine baghouse ash

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

The contribution of X-linked coding variation to severe developmental disorders

Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders