Current warming will reduce yields unless maize breeding and seed systems adapt immediately

The development of crop varieties that are better suited to new climatic conditions is vital for future food production1, 2. Increases in mean temperature accelerate crop development, resulting in shorter crop durations and reduced time to accumulate biomass and yield3, 4. The process of breeding, delivery and adoption (BDA) of new maize varieties can take up to 30 years. Here, we assess for the first time the implications of warming during the BDA process by using five bias-corrected global climate models and four representative concentration pathways with realistic scenarios of maize BDA times in Africa. The results show that the projected difference in temperature between the start and end of the maize BDA cycle results in shorter crop durations that are outside current variability. Both adaptation and mitigation can reduce duration loss. In particular, climate projections have the potential to provide target elevated temperatures for breeding. Whilst options for reducing BDA time are highly context dependent, common threads include improved recording and sharing of data across regions for the whole BDA cycle, streamlining of regulation, and capacity building. Finally, we show that the results have implications for maize across the tropics, where similar shortening of duration is projected

The impact of statins on health services utilization and mortality in older adults discharged from hospital with ischemic heart disease: a cohort study

<p>Abstract</p> <p>Background</p> <p>Cardiovascular disease (CVD) carries a high burden of morbidity and mortality and is associated with significant utilization of health care resources, especially in the elderly. Numerous randomized trials have established the efficacy of cholesterol reduction with statin medications in decreasing mortality in high-risk populations. However, it is not known what the effect of the utilization of these medications in complex older adults has had on mortality and on the utilization of health services, such as physician visits, hospitalizations or cardiovascular procedures.</p> <p>Methods</p> <p>This project linked clinical and hospital data from the Improving Cardiovascular Outcomes in Nova Scotia (ICONS) database with administrative data from the Population Health Research Unit to identify all older adults hospitalized with ischemic heart disease between October 15, 1997 and March 31, 2001. All patients were followed for at least one year or until death. Multiple regression techniques, including Cox proportional hazards models and generalized linear models were employed to compare health services utilization and mortality for statin users and non-statin users.</p> <p>Results</p> <p>Of 4232 older adults discharged alive from the hospital, 1629 (38%) received a statin after discharge. In multivariate models after adjustment for demographic and clinical characteristics, and propensity score, statins were associated with a 26% reduction in all- cause mortality (hazard ratio (HR) 0.74, 95% confidence interval (CI) 0.63-0.88). However, statin use was not associated with subsequent reductions in health service utilization, including re-hospitalizations (HR, 0.98, 95% CI 0.91-1.06), physician visits (relative risk (RR) 0.97, 95% CI 0.92-1.02) or coronary revascularization procedures (HR 1.15, 95% CI 0.97-1.36).</p> <p>Conclusion</p> <p>As the utilization of statins continues to grow, their impact on the health care system will continue to be important. Future studies are needed to continue to ensure that those who would realize significant benefit from the medication receive it.</p

Cortactin Phosphorylated by ERK1/2 Localizes to Sites of Dynamic Actin Regulation and Is Required for Carcinoma Lamellipodia Persistence

Tumor cell motility and invasion is governed by dynamic regulation of the cortical actin cytoskeleton. The actin-binding protein cortactin is commonly upregulated in multiple cancer types and is associated with increased cell migration. Cortactin regulates actin nucleation through the actin related protein (Arp)2/3 complex and stabilizes the cortical actin cytoskeleton. Cortactin is regulated by multiple phosphorylation events, including phosphorylation of S405 and S418 by extracellular regulated kinases (ERK)1/2. ERK1/2 phosphorylation of cortactin has emerged as an important positive regulatory modification, enabling cortactin to bind and activate the Arp2/3 regulator neuronal Wiskott-Aldrich syndrome protein (N-WASp), promoting actin polymerization and enhancing tumor cell movement.In this report we have developed phosphorylation-specific antibodies against phosphorylated cortactin S405 and S418 to analyze the subcellular localization of this cortactin form in tumor cells and patient samples by microscopy. We evaluated the interplay between cortactin S405 and S418 phosphorylation with cortactin tyrosine phosphorylation in regulating cortactin conformational forms by Western blotting. Cortactin is simultaneously phosphorylated at S405/418 and Y421 in tumor cells, and through the use of point mutant constructs we determined that serine and tyrosine phosphorylation events lack any co-dependency. Expression of S405/418 phosphorylation-null constructs impaired carcinoma motility and adhesion, and also inhibited lamellipodia persistence monitored by live cell imaging.Cortactin phosphorylated at S405/418 is localized to sites of dynamic actin assembly in tumor cells. Concurrent phosphorylation of cortactin by ERK1/2 and tyrosine kinases enables cells with the ability to regulate actin dynamics through N-WASp and other effector proteins by synchronizing upstream regulatory pathways, confirming cortactin as an important integration point in actin-based signal transduction. Reduced lamellipodia persistence in cells with S405/418A expression identifies an essential motility-based process reliant on ERK1/2 signaling, providing additional understanding as to how this pathway impacts tumor cell migration

Classification and Regression Tree and Spatial Analyses Reveal Geographic Heterogeneity in Genome Wide Linkage Study of Indian Visceral Leishmaniasis

Genome wide linkage studies (GWLS) have provided evidence for loci controlling visceral leishmaniasis on Chromosomes 1p22, 6q27, 22q12 in Sudan and 6q27, 9p21, 17q11-q21 in Brazil. Genome wide studies from the major focus of disease in India have not previously been reported.We undertook a GWLS in India in which a primary ∼10 cM (515 microsatellites) scan was carried out in 58 multicase pedigrees (74 nuclear families; 176 affected, 353 total individuals) and replication sought in 79 pedigrees (102 nuclear families; 218 affected, 473 total individuals). The primary scan provided evidence (≥2 adjacent markers allele-sharing LOD≥0.59; nominal P≤0.05) for linkage on Chromosomes 2, 5, 6, 7, 8, 10, 11, 20 and X, with peaks at 6p25.3-p24.3 and 8p23.1-p21.3 contributed to largely by 31 Hindu families and at Xq21.1-q26.1 by 27 Muslim families. Refined mapping confirmed linkage across all primary scan families at 2q12.2-q14.1 and 11q13.2-q23.3, but only 11q13.2-q23.3 replicated (combined LOD = 1.59; P = 0.0034). Linkage at 6p25.3-p24.3 and 8p23.1-p21.3, and at Xq21.1-q26.1, was confirmed by refined mapping for primary Hindu and Muslim families, respectively, but only Xq21.1-q26.1 replicated across all Muslim families (combined LOD 1.49; P = 0.0045). STRUCTURE and SMARTPCA did not identify population genetic substructure related to religious group. Classification and regression tree, and spatial interpolation, analyses confirm geographical heterogeneity for linkages at 6p25.3-p24.3, 8p23.1-p21.3 and Xq21.1-q26.1, with specific clusters of families contributing LOD scores of 2.13 (P = 0.0009), 1.75 (P = 0.002) and 1.84 (P = 0.001), respectively.GWLS has identified novel loci that show geographical heterogeneity in their influence on susceptibility to VL in India

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified