Accounting for the economic risk, caused by variation in disease severity, in fungicide dose decisions: exemplified for Mycosphaerella graminicola on winter wheat

A method is presented to calculate economic optimum fungicide doses accounting for the risk-aversion of growers responding to variability in disease severity between crops. Simple dose-response and disease-yield loss functions are used to estimate net disease-related costs (fungicide cost, plus disease-induced yield loss) as a function of dose and untreated severity. With fairly general assumptions about the shapes of the probability distribution of disease severity and the other functions involved, we show that a choice of fungicide dose which minimises net costs on average across seasons results in occasional large net costs caused by inadequate control in high disease seasons. This may be unacceptable to a grower with limited capital. A risk-averse grower can choose to reduce the size and frequency of such losses by applying a higher dose as insurance. For example, a grower may decide to accept ‘high loss’ years one year in ten or one year in twenty (i.e. specifying a proportion of years in which disease severity and net costs will be above a specified level). Our analysis shows that taking into account disease severity variation and risk-aversion will usually increase the dose applied by an economically rational grower. The analysis is illustrated with data on septoria tritici leaf blotch of wheat caused by Mycosphaerella graminicola. Observations from untreated field plots at sites across England over three years were used to estimate the probability distribution of disease severities at mid-grain filling. In the absence of a fully reliable disease forecasting scheme, reducing the frequency of ‘high loss’ years requires substantially higher doses to be applied to all crops. Disease resistant cultivars reduce both the optimal dose at all levels of risk and the disease-related costs at all doses.

Ethnic differences in beta-cell function, dietary intake and expression of the metabolic syndrome among UK adults of south Asian, black African-Caribbean and white-European origin at high risk of metabolic syndrome

A cross-sectional analysis of ethnic differences in dietary intake, insulin sensitivity and beta-cell function, using the intravenous glucose tolerance test (IVGTT), was conducted on 497 healthy adult participants of the ‘Reading, Imperial, Surrey, Cambridge, and Kings’ (RISCK) study. Insulin sensitivity (Si) was significantly lower in African-Caribbean (AC) and South Asian (SA) participants [IVGTT-Si; AC: 2.13 vs SA: 2.25 vs white-European (WE): 2.84 (×10−4 mL µU min)2, p < 0.001]. AC participants had a higher prevalence of anti-hypertensive therapy (AC: 19.7% vs SA: 7.5%), the most cardioprotective lipid profile [total:high-density lipoprotein (HDL); AC: 3.52 vs SA: 4.08 vs WE: 3.83, p = 0.03] and more pronounced hyperinsulinaemia [IVGTT–acute insulin response (AIR)] [AC: 575 vs SA: 428 vs WE: 344 mL/µU/min)2, p = 0.002], specifically in female participants. Intake of saturated fat and carbohydrate was lower and higher in AC (10.9% and 50.4%) and SA (11.1% and 52.3%), respectively, compared to WE (13.6% and 43.8%, p < 0.001). Insulin resistance in ACs is characterised by ‘normal’ lipid profiles but high rates of hypertension and pronounced hyperinsulinaemia.

Interaction between allelic variations in vitamin D receptor and retinoid X receptor genes on metabolic traits

BACKGROUND: Low vitamin D status has been shown to be a risk factor for several metabolic traits such as obesity, diabetes and cardiovascular disease. The biological actions of 1, 25-dihydroxyvitamin D, are mediated through the vitamin D receptor (VDR), which heterodimerizes with retinoid X receptor, gamma (RXRG). Hence, we examined the potential interactions between the tagging polymorphisms in the VDR (22 tag SNPs) and RXRG (23 tag SNPs) genes on metabolic outcomes such as body mass index, waist circumference, waist-hip ratio (WHR), high- and low-density lipoprotein (LDL) cholesterols, serum triglycerides, systolic and diastolic blood pressures and glycated haemoglobin in the 1958 British Birth Cohort (1958BC, up to n = 5,231). We used Multifactor- dimensionality reduction (MDR) program as a non-parametric test to examine for potential interactions between the VDR and RXRG gene polymorphisms in the 1958BC. We used the data from Northern Finland Birth Cohort 1966 (NFBC66, up to n = 5,316) and Twins UK (up to n = 3,943) to replicate our initial findings from 1958BC. RESULTS: After Bonferroni correction, the joint-likelihood ratio test suggested interactions on serum triglycerides (4 SNP - SNP pairs), LDL cholesterol (2 SNP - SNP pairs) and WHR (1 SNP - SNP pair) in the 1958BC. MDR permutation model testing analysis showed one two-way and one three-way interaction to be statistically significant on serum triglycerides in the 1958BC. In meta-analysis of results from two replication cohorts (NFBC66 and Twins UK, total n = 8,183), none of the interactions remained after correction for multiple testing (Pinteraction >0.17). CONCLUSIONS: Our results did not provide strong evidence for interactions between allelic variations in VDR and RXRG genes on metabolic outcomes; however, further replication studies on large samples are needed to confirm our findings.

Interactions between lipid-free apolipoprotein-AI and a lipopeptide incorporating the RGDS cell adhesion motif

The interaction of a designed bioactive lipopeptide C16-GGGRGDS, comprising a hexadecyl lipid chain attached to a functional heptapeptide, with the lipid-free apoliprotein, Apo-AI, is examined. This apolipoprotein is a major component of high density lipoprotein and it is involved in lipid metabolism and may serve as a biomarker for cardiovascular disease and Alzheimers’ disease. We find via isothermal titration calorimetry that binding between the lipopeptide and Apo-AI occurs up to a saturation condition, just above equimolar for a 10.7 μM concentration of Apo-AI. A similar value is obtained from circular dichroism spectroscopy, which probes the reduction in α-helical secondary structure of Apo-AI upon addition of C16-GGGRGDS. Electron microscopy images show a persistence of fibrillar structures due to self-assembly of C16-GGGRGDS in mixtures with Apo-AI above the saturation binding condition. A small fraction of spheroidal or possibly “nanodisc” structures was observed. Small-angle X-ray scattering (SAXS) data for Apo-AI can be fitted using a published crystal structure of the Apo-AI dimer. The SAXS data for the lipopeptide/ Apo-AI mixtures above the saturation binding conditions can be fitted to the contribution from fibrillar structures coexisting with flat discs corresponding to Apo-AI/lipopeptide aggregates.

Effect of cinnamon on gastric emptying, arterial stiffness, postprandial lipemia, glycemia, and appetite responses to high-fat breakfast

Abstract BACKGROUND: Cinnamon has been shown to delay gastric emptying of a high-carbohydrate meal and reduce postprandial glycemia in healthy adults. However, it is dietary fat which is implicated in the etiology and is associated with obesity, type 2 diabetes and cardiovascular disease. We aimed to determine the effect of 3 g cinnamon (Cinnamomum zeylanicum) on GE, postprandial lipemic and glycemic responses, oxidative stress, arterial stiffness, as well as appetite sensations and subsequent food intake following a high-fat meal. METHODS: A single-blind randomized crossover study assessed nine healthy, young subjects. GE rate of a high-fat meal supplemented with 3 g cinnamon or placebo was determined using the 13C octanoic acid breath test. Breath, blood samples and subjective appetite ratings were collected in the fasted and during the 360 min postprandial period, followed by an ad libitum buffet meal. Gastric emptying and 1-day fatty acid intake relationships were also examined. RESULTS: Cinnamon did not change gastric emptying parameters, postprandial triacylglycerol or glucose concentrations, oxidative stress, arterial function or appetite (p < 0.05). Strong relationships were evident (p < 0.05) between GE Thalf and 1-day palmitoleic acid (r = -0.78), eiconsenoic acid (r = -0.84) and total omega-3 intake (r = -0.72). The ingestion of 3 g cinnamon had no effect on GE, arterial stiffness and oxidative stress following a HF meal. CONCLUSIONS: 3 g cinnamon did not alter the postprandial response to a high-fat test meal. We find no evidence to support the use of 3 g cinnamon supplementation for the prevention or treatment of metabolic disease. Dietary fatty acid intake requires consideration in future gastrointestinal studies.

Effect of azole fungicide mixtures, alternations and dose on azole sensitivity in the wheat pathogen Zymoseptoria tritici

The evolution of fungicide resistance in the cereal pathogen Zymoseptoria tritici, is a serious threat to the sustainability and profitability of wheat production in Europe. Application of azole fungicides has been shown to affect fitness of Z. tritici variants differentially, so it has been hypothesised that combinations of azoles could slow the evolution of resistance. This work was initiated to assess the effects of dose, mixtures and alternations of two azoles on selection for isolates with reduced sensitivity and on disease control. Naturally infected field trials were carried out at six sites across Ireland and the sensitivity of Z. tritici isolates monitored pre- and post-treatment. The azoles epoxiconazole and metconazole were applied as solo products, in alternation with each other and as a pre-formulated mixture. Full and half label doses were tested. The two azoles were partially cross-resistant, with a common azole resistance principal component accounting for 75% of the variation between isolates. Selection for isolates with reduced azole sensitivity was correlated with disease control. Decreased doses were related to decreases in sensitivity but the effect was barely significant (P = 0.1) and control was reduced. Single applications of an active ingredient (a.i.) caused smaller decreases in sensitivity than double applications. Shifts in sensitivity to the a.i. applied to a plot were greater than to the a.i. not applied, and the decrease in sensitivity was greater to the a.i. applied at the second timing. These results confirm the need to mix a.i.s with different modes of action.

A review of the cognitive effects observed in humans following acute supplementation with flavonoids, and their associated mechanisms of action

Flavonoids are polyphenolic compounds found in varying concentrations in many plant-based foods. Recent studies suggest that flavonoids can be beneficial to both cognitive and physiological health. Long term flavonoid supplementation over a period of weeks or months has been extensively investigated and reviewed, particularly with respect to cognitive ageing and neurodegenerative disease. Significantly less focus has been directed towards the short term effects of single doses of flavonoids on cognition. Here, we review 21 such studies with particular emphasis on the subclass and dose of flavonoids administered, the cognitive domains affected by flavonoid supplementation, and the effect size of the response. The emerging evidence suggests that flavonoids may be beneficial to attention, working memory, and psychomotor processing speed in a general population. Episodic memory effects are less well defined and may be restricted to child or older adult populations. The evidence also points towards a dose-dependent effect of flavonoids, but the physiological mechanisms of action remain unclear. Overall, there is encouraging evidence that flavonoid supplementation can benefit cognitive outcomes within an acute time frame of 0–6 h. But larger studies, combining cognitive and physiological measures, are needed to strengthen the evidence base.

Work and the adolescent in medieval England (AD 900-1550). The osteological evidence

What was it like to be a teenager in medieval England? Despite the fact that medieval society often singled young apprentices and workers out for comment, their study has been largely neglected in medieval archaeology. The skeletal remains of 4940 adolescents (6.6-25 years) from 151 sites in medieval England was compiled from a combination of primary data collection and secondary data from published and unpublished skeletal reports and on-line databases. The aim was to explore whether apprentices could be identified in the archaeological record and if so, at what age they started work and what impact occupation had on their health. The data were divided into urban and rural groups, dating from before and after the Black Death of AD 1348-9, and before the Industrial Revolution. A shift in the demographic pattern of urban and rural adolescents was identified after the Black Death, with a greater number of young females residing in the urban contexts after 14 years. The average age of males increased from 12 years to 14 years after the plague years, contrary to what we might expect from the documentary sources. There were higher rates of spinal and joint disease in the urban adolescents and their injuries were more widespread than their rural counterparts. Domestic service was the potential cause of the greater strain on the knees and backs of the urban females, with interpersonal violence evident in the young urban males. Overall, it was the urban females that carried the burden of respiratory and infectious diseases suggesting they may have been the most vulnerable group. This study has demonstrated the value of adolescent skeletal remains in revealing information about their health and working life, before and after the Black Death.

Commentary: not just genes - reclaiming a role for environmental influences on aetiology and outcome in autism. A commentary on Mandy and Lai (2016)

Mandy and Lai (2015) do the field a service in 'reclaiming' the role of pre- and postnatal environmental influences on the aetiology and course of autism spectrum conditions (ASC). This follows several decades where now discredited theories about putative psychogenic and biological disease models held sway, not least in the public mind. We discuss issues that arise from their review; including the need to identify how large the environmental influences on ASC are likely to be; the specificity of these environmental influences to ASC as opposed to a broader range of neurodevelopmental conditions and outcomes; how best to study complex interactions between genetic and environmental influences; and the promise of novel insights into their mechanisms of action. The review highlights current research that aims to better our understanding of the role of environmental factors in the aetiology and course of ASC and, in the near future, may offer the potential for personalised medicine approaches to intervention based on these discoveries.