Summary
Wheat is the most widely grown crop globally, providing 20% of all human calories and protein. Achieving step changes in genetic yield potential is crucial to ensure food security, but ...efforts are thwarted by an apparent trade‐off between grain size and number. Expansins are proteins that play important roles in plant growth by enhancing stress relaxation in the cell wall, which constrains cell expansion.
Here, we describe how targeted overexpression of an α‐expansin in early developing wheat seeds leads to a significant increase in grain size without a negative effect on grain number, resulting in a yield boost under field conditions.
The best‐performing transgenic line yielded 12.3% higher average grain weight than the control, and this translated to an increase in grain yield of 11.3% in field experiments using an agronomically appropriate plant density.
This targeted transgenic approach provides an opportunity to overcome a common bottleneck to yield improvement across many crops.
See also the Commentary on this article by Cosgrove, 230: 403‐405.
Summary Background The contribution of various risk factors to the burden of stroke worldwide is unknown, particularly in countries of low and middle income. We aimed to establish the association of ...known and emerging risk factors with stroke and its primary subtypes, assess the contribution of these risk factors to the burden of stroke, and explore the differences between risk factors for stroke and myocardial infarction. Methods We undertook a standardised case-control study in 22 countries worldwide between March 1, 2007, and April 23, 2010. Cases were patients with acute first stroke (within 5 days of symptoms onset and 72 h of hospital admission). Controls had no history of stroke, and were matched with cases for age and sex. All participants completed a structured questionnaire and a physical examination, and most provided blood and urine samples. We calculated odds ratios (ORs) and population-attributable risks (PARs) for the association of all stroke, ischaemic stroke, and intracerebral haemorrhagic stroke with selected risk factors. Findings In the first 3000 cases (n=2337, 78%, with ischaemic stroke; n=663, 22%, with intracerebral haemorrhagic stroke) and 3000 controls, significant risk factors for all stroke were: history of hypertension (OR 2·64, 99% CI 2·26–3·08; PAR 34·6%, 99% CI 30·4–39·1); current smoking (2·09, 1·75–2·51; 18·9%, 15·3–23·1); waist-to-hip ratio (1·65, 1·36–1·99 for highest vs lowest tertile; 26·5%, 18·8–36·0); diet risk score (1·35, 1·11–1·64 for highest vs lowest tertile; 18·8%, 11·2–29·7); regular physical activity (0·69, 0·53–0·90; 28·5%, 14·5–48·5); diabetes mellitus (1·36, 1·10–1·68; 5·0%, 2·6–9·5); alcohol intake (1·51, 1·18–1·92 for more than 30 drinks per month or binge drinking; 3·8%, 0·9–14·4); psychosocial stress (1·30, 1·06–1·60; 4·6%, 2·1–9·6) and depression (1·35, 1·10–1·66; 5·2%, 2·7–9·8); cardiac causes (2·38, 1·77–3·20; 6·7%, 4·8–9·1); and ratio of apolipoproteins B to A1 (1·89, 1·49–2·40 for highest vs lowest tertile; 24·9%, 15·7–37·1). Collectively, these risk factors accounted for 88·1% (99% CI 82·3–92·2) of the PAR for all stroke. When an alternate definition of hypertension was used (history of hypertension or blood pressure >160/90 mm Hg), the combined PAR was 90·3% (85·3–93·7) for all stroke. These risk factors were all significant for ischaemic stroke, whereas hypertension, smoking, waist-to-hip ratio, diet, and alcohol intake were significant risk factors for intracerebral haemorrhagic stroke. Interpretation Our findings suggest that ten risk factors are associated with 90% of the risk of stroke. Targeted interventions that reduce blood pressure and smoking, and promote physical activity and a healthy diet, could substantially reduce the burden of stroke. Funding Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Pfizer Cardiovascular Award, Merck, AstraZeneca, and Boehringer Ingelheim.
Little is known about the relationship between perioperative high-sensitivity troponin T (hsTnT) measurements and 30-day mortality and myocardial injury after noncardiac surgery (MINS).
To determine ...the association between perioperative hsTnT measurements and 30-day mortality and potential diagnostic criteria for MINS (ie, myocardial injury due to ischemia associated with 30-day mortality).
Prospective cohort study of patients aged 45 years or older who underwent inpatient noncardiac surgery and had a postoperative hsTnT measurement. Starting in October 2008, participants were recruited at 23 centers in 13 countries; follow-up finished in December 2013.
Patients had hsTnT measurements 6 to 12 hours after surgery and daily for 3 days; 40.4% had a preoperative hsTnT measurement.
A modified Mazumdar approach (an iterative process) was used to determine if there were hsTnT thresholds associated with risk of death and had an adjusted hazard ratio (HR) of 3.0 or higher and a risk of 30-day mortality of 3% or higher. To determine potential diagnostic criteria for MINS, regression analyses ascertained if postoperative hsTnT elevations required an ischemic feature (eg, ischemic symptom or electrocardiography finding) to be associated with 30-day mortality.
Among 21 842 participants, the mean age was 63.1 (SD, 10.7) years and 49.1% were female. Death within 30 days after surgery occurred in 266 patients (1.2%; 95% CI, 1.1%-1.4%). Multivariable analysis demonstrated that compared with the reference group (peak hsTnT <5 ng/L), peak postoperative hsTnT levels of 20 to less than 65 ng/L, 65 to less than 1000 ng/L, and 1000 ng/L or higher had 30-day mortality rates of 3.0% (123/4049; 95% CI, 2.6%-3.6%), 9.1% (102/1118; 95% CI, 7.6%-11.0%), and 29.6% (16/54; 95% CI, 19.1%-42.8%), with corresponding adjusted HRs of 23.63 (95% CI, 10.32-54.09), 70.34 (95% CI, 30.60-161.71), and 227.01 (95% CI, 87.35-589.92), respectively. An absolute hsTnT change of 5 ng/L or higher was associated with an increased risk of 30-day mortality (adjusted HR, 4.69; 95% CI, 3.52-6.25). An elevated postoperative hsTnT (ie, 20 to <65 ng/L with an absolute change ≥5 ng/L or hsTnT ≥65 ng/L) without an ischemic feature was associated with 30-day mortality (adjusted HR, 3.20; 95% CI, 2.37-4.32). Among the 3904 patients (17.9%; 95% CI, 17.4%-18.4%) with MINS, 3633 (93.1%; 95% CI, 92.2%-93.8%) did not experience an ischemic symptom.
Among patients undergoing noncardiac surgery, peak postoperative hsTnT during the first 3 days after surgery was significantly associated with 30-day mortality. Elevated postoperative hsTnT without an ischemic feature was also associated with 30-day mortality.
The optimal range of sodium intake for cardiovascular health is controversial.
We obtained morning fasting urine samples from 101,945 persons in 17 countries and estimated 24-hour sodium and ...potassium excretion (used as a surrogate for intake). We examined the association between estimated urinary sodium and potassium excretion and the composite outcome of death and major cardiovascular events.
The mean estimated sodium and potassium excretion was 4.93 g per day and 2.12 g per day, respectively. With a mean follow-up of 3.7 years, the composite outcome occurred in 3317 participants (3.3%). As compared with an estimated sodium excretion of 4.00 to 5.99 g per day (reference range), a higher estimated sodium excretion (≥ 7.00 g per day) was associated with an increased risk of the composite outcome (odds ratio, 1.15; 95% confidence interval CI, 1.02 to 1.30), as well as increased risks of death and major cardiovascular events considered separately. The association between a high estimated sodium excretion and the composite outcome was strongest among participants with hypertension (P=0.02 for interaction), with an increased risk at an estimated sodium excretion of 6.00 g or more per day. As compared with the reference range, an estimated sodium excretion that was below 3.00 g per day was also associated with an increased risk of the composite outcome (odds ratio, 1.27; 95% CI, 1.12 to 1.44). As compared with an estimated potassium excretion that was less than 1.50 g per day, higher potassium excretion was associated with a reduced risk of the composite outcome.
In this study in which sodium intake was estimated on the basis of measured urinary excretion, an estimated sodium intake between 3 g per day and 6 g per day was associated with a lower risk of death and cardiovascular events than was either a higher or lower estimated level of intake. As compared with an estimated potassium excretion that was less than 1.50 g per day, higher potassium excretion was associated with a lower risk of death and cardiovascular events. (Funded by the Population Health Research Institute and others.).
Abstract Objectives Whether non-HDL-C and apoB are equivalent markers of cardiovascular risk remains controversial. Only when apoB particles in toto contain either more or less cholesterol than ...normal – that is, when their composition is discordant – could apoB and non-HDL-C predict risk differently. Accordingly, this study tests within the INTERHEART data base whether apoB or non-HDL-C are equivalent markers of risk when the two markers are discordant. Methods The INTERHEART study is a standardized case-control study of acute myocardial infarction with blood samples in 9345 cases and 12,120 controls from 52 countries. To produce comparability, the concentrations of non-HDL-C and apoB are expressed as percentiles (P) within the study population. Concordance is defined as the phenotype when P Non-HDL-C = P apoB (that is, apoB particles contain a normal mass of cholesterol). Discordance is defined either as the phenotype when P Non-HDL-C > P apoB (cholesterol-enriched apoB particles) or P Non-HDL-C < P apoB (cholesterol-depleted apoB particles). The OR of cases to controls was determined for both discordant groups and compared to the ratio of cases to controls in the concordant group, which was the reference group. An OR > 1 means that risk is greater in the discordant than in the reference phenotype whereas an OR < 1 means the cases are less common in the discordant phenotype than in the reference group. Results When discordance was defined as percentiles within 5%, a definition that produced equal numbers of discordant and concordant individuals, the OR for P Non-HDL-C > apoB (cholesterol-enriched apoB particles) was 0.72 (0.67–0.77 95% CI) indicating risk was less than the reference concordant group whereas the OR for P Non-HDL-C < apoB (cholesterol-depleted apoB particles) was 1.58 (1.38–1.58 95% CI) indicating risk was significantly greater than the reference concordant group. The same findings were reproduced using all definitions of discordance from 1% to 10%. Moreover, the pattern of findings was consistent amongst the ethnic groups that made up the overall study population. Conclusion Discordance analysis demonstrates that apoB is a more accurate marker of cardiovascular risk than non-HDL-C.
Whether apolipoprotein B (apoB) or non-high-density lipoprotein cholesterol (HDL-C) adds to the predictive power of low-density lipoprotein cholesterol (LDL-C) for cardiovascular risk remains ...controversial.
This meta-analysis is based on all the published epidemiological studies that contained estimates of the relative risks of non-HDL-C and apoB of fatal or nonfatal ischemic cardiovascular events. Twelve independent reports, including 233 455 subjects and 22 950 events, were analyzed. All published risk estimates were converted to standardized relative risk ratios (RRRs) and analyzed by quantitative meta-analysis using a random-effects model. Whether analyzed individually or in head-to-head comparisons, apoB was the most potent marker of cardiovascular risk (RRR, 1.43; 95% CI, 1.35 to 1.51), LDL-C was the least (RRR, 1.25; 95% CI, 1.18 to 1.33), and non-HDL-C was intermediate (RRR, 1.34; 95% CI, 1.24 to 1.44). The overall comparisons of the within-study differences showed that apoB RRR was 5.7%>non-HDL-C (P<0.001) and 12.0%>LDL-C (P<0.0001) and that non-HDL-C RRR was 5.0%>LDL-C (P=0.017). Only HDL-C accounted for any substantial portion of the variance of the results among the studies. We calculated the number of clinical events prevented by a high-risk treatment regimen of all those >70th percentile of the US adult population using each of the 3 markers. Over a 10-year period, a non-HDL-C strategy would prevent 300 000 more events than an LDL-C strategy, whereas an apoB strategy would prevent 500 000 more events than a non-HDL-C strategy.
These results further validate the value of apoB in clinical care.
Abstract Background Microflora-dependent trimethylamine-N-oxide (TMAO) formation, which results from intake of choline and L-carnitine-rich food, shows promise as a predictor of cardiovascular ...disease (CVD) risk, but these associations have not been examined in ethnically diverse populations. In a multiethnic population-based study of adults in Canada, we assessed the stability of TMAO and L-carnitine in stored serum samples and their association with intimal medial thickness, prevalent risk factors, and clinical events. Methods In a randomly sampled cross-sectional study of 1286 Canadians, fasting serum samples were collected and stored. In 292 consecutive individuals (99 CVD cases and 193 unmatched control subjects), L-carnitine and TMAO concentrations were assessed using validated analytical approaches. Results The mean (± SD) TMAO level was 1.998 ± 3.13 μM and L-carnitine was 42.29 ± 11.35 μM. The relative levels of the samples did not appreciably change after 3 freeze-thaw cycles (coefficient of variation, 5.6% and 4.7%, respectively). No significant association between L-carnitine levels and prevalent CVD was found, with adjustment for covariates (odds ratio, 1.57; 95% confidence interval, 0.58-4.26; P trend = 0.65), for highest vs lowest quintile group. TMAO levels showed a significant, graded association with prevalent CVD (odds ratio, 3.17; 95% confidence interval, 1.05-9.51; P trend = 0.02). After further adjustment for diabetes status, meat, fish, and cholesterol intake, the association remained significant. No significant association between carotid intimal medial thickness and L-carnitine ( P = 0.64) or TMAO ( P = 0.18) was found. Conclusions Serum TMAO and L-carnitine analysis on stored samples is reliable. Our findings support an association between TMAO with prevalent CVD in a multiethnic population. This finding requires replication in larger studies in which dietary intake and stored serum samples exist.
Of the 200 million adults worldwide who undergo noncardiac surgery each year, more than 1 million will die within 30 days.
To determine the relationship between the peak fourth-generation troponin T ...(TnT) measurement in the first 3 days after noncardiac surgery and 30-day mortality.
A prospective, international cohort study that enrolled patients from August 6, 2007, to January 11, 2011. Eligible patients were aged 45 years and older and required at least an overnight hospital admission after having noncardiac surgery.
Patients' TnT levels were measured 6 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We undertook Cox regression analysis in which the dependent variable was mortality until 30 days after surgery, and the independent variables included 24 preoperative variables. We repeated this analysis, adding the peak TnT measurement during the first 3 postoperative days as an independent variable and used a minimum P value approach to determine if there were TnT thresholds that independently altered patients' risk of death.
A total of 15,133 patients were included in this study. The 30-day mortality rate was 1.9% (95% CI, 1.7%-2.1%). Multivariable analysis demonstrated that peak TnT values of at least 0.02 ng/mL, occurring in 11.6% of patients, were associated with higher 30-day mortality compared with the reference group (peak TnT ≤ 0.01 ng/mL): peak TnT of 0.02 ng/mL (adjusted hazard ratio aHR, 2.41; 95% CI, 1.33-3.77); 0.03 to 0.29 ng/mL (aHR, 5.00; 95% CI, 3.72-6.76); and 0.30 ng/mL or greater (aHR, 10.48; 95% CI, 6.25-16.62). Patients with a peak TnT value of 0.01 ng/mL or less, 0.02, 0.03-0.29, and 0.30 or greater had 30-day mortality rates of 1.0%, 4.0%, 9.3%, and 16.9%, respectively. Peak TnT measurement added incremental prognostic value to discriminate those likely to die within 30 days for the model with peak TnT measurement vs without (C index = 0.85 vs 0.81; difference, 0.4; 95% CI, 0.2-0.5; P < .001 for difference between C index values). The net reclassification improvement with TnT was 25.0% (P < .001).
Among patients undergoing noncardiac surgery, the peak postoperative TnT measurement during the first 3 days after surgery was significantly associated with 30-day mortality.
Higher levels of sodium intake are reported to be associated with higher blood pressure. Whether this relationship varies according to levels of sodium or potassium intake and in different ...populations is unknown.
We studied 102,216 adults from 18 countries. Estimates of 24-hour sodium and potassium excretion were made from a single fasting morning urine specimen and were used as surrogates for intake. We assessed the relationship between electrolyte excretion and blood pressure, as measured with an automated device.
Regression analyses showed increments of 2.11 mm Hg in systolic blood pressure and 0.78 mm Hg in diastolic blood pressure for each 1-g increment in estimated sodium excretion. The slope of this association was steeper with higher sodium intake (an increment of 2.58 mm Hg in systolic blood pressure per gram for sodium excretion >5 g per day, 1.74 mm Hg per gram for 3 to 5 g per day, and 0.74 mm Hg per gram for <3 g per day; P<0.001 for interaction). The slope of association was steeper for persons with hypertension (2.49 mm Hg per gram) than for those without hypertension (1.30 mm Hg per gram, P<0.001 for interaction) and was steeper with increased age (2.97 mm Hg per gram at >55 years of age, 2.43 mm Hg per gram at 45 to 55 years of age, and 1.96 mm Hg per gram at <45 years of age; P<0.001 for interaction). Potassium excretion was inversely associated with systolic blood pressure, with a steeper slope of association for persons with hypertension than for those without it (P<0.001) and a steeper slope with increased age (P<0.001).
In this study, the association of estimated intake of sodium and potassium, as determined from measurements of excretion of these cations, with blood pressure was nonlinear and was most pronounced in persons consuming high-sodium diets, persons with hypertension, and older persons. (Funded by the Heart and Stroke Foundation of Ontario and others.).
Summary Background Whether lipoproteins are better markers than lipids and lipoproteins for coronary heart disease is widely debated. Our aim was to compare the apolipoproteins and cholesterol as ...indices for risk of acute myocardial infarction. Methods We did a large, standardised case-control study of acute myocardial infarction in 12 461 cases and 14 637 age-matched (plus or minus 5 years) and sex-matched controls in 52 countries. Non-fasting blood samples were available from 9345 cases and 12 120 controls. Concentrations of plasma lipids, lipoproteins, and apolipoproteins were measured, and cholesterol and apolipoprotein ratios were calculated. Odds ratios (OR) and 95% CI, and population-attributable risks (PARs) were calculated for each measure overall and for each ethnic group by comparison of the top four quintiles with the lowest quintile. Findings The apolipoprotein B100 (ApoB)/apolipoprotein A1 (ApoA1) ratio had the highest PAR (54%) and the highest OR with each 1 SD difference (1·59, 95% CI 1·53–1·64). The PAR for ratio of LDL cholesterol/HDL cholesterol was 37%. PAR for total cholesterol/HDL cholesterol was 32%, which was substantially lower than that of the ApoB/ApoA1 ratio (p<0·0001). These results were consistent in all ethnic groups, men and women, and for all ages. Interpretation The non-fasting ApoB/ApoA1 ratio was superior to any of the cholesterol ratios for estimation of the risk of acute myocardial infarction in all ethnic groups, in both sexes, and at all ages, and it should be introduced into worldwide clinical practice. Funding Canadian Institutes of Health Research, the Heart and Stroke Foundation of Ontario, the International Clinical Epidemiology Network (INCLEN). Unrestricted grants from pharmaceutical companies (with major contributions from AstraZeneca, Novartis, Aventis, Abbott, Bristol Myers Squibb, King Pharma, and Sanofi-Synthelabo), and by various national bodies.
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