QTL identification and candidate gene identification for monoterpene content in grape (Vitis vinifera L.) berries

Great progress has been made during the last decade in clarifying the molecular details of aroma accumulation in grape berries. However, the multigene complex controlling monoterpene accumulation in grape is not well understood. To shed light on this issue, the grapes of 149 F1 progenies from the cross 87-1 (Vitis vinifera L.) × 9-22 (Vitis vinifera L.) were characterized at the mature stage for three representative free monoterpenes during five growing seasons. A total of 202, 184 and 255 polymorphic SSR (simple sequence repeat) markers were contracted on the maternal 87-1, paternal 9-22 and consensus genetic maps, respectively. On the consensus map, we confirmed a major QTL (quantitative trait locus) for free linalool, nerol and α-terpineol content on linkage group (LG) 5, and a stable QTL for free linalool and α-terpineol was detected on LG 10. In addition, two new stable QTLs for free monoterpene (linalool, nerol and α-terpineol) contents were identified on LG 11 and LG 18 that explained up to 42.5 % of the total variance. Eleven promising candidate genes related to pentatricopeptide repeat (PPR)-containing proteins, seed maturation protein, RING finger protein, and AP2/ERF transcription factors might be potentially involved in monoterpene accumulation. The stable QTLs and candidate genes identified in this study provide new insights into free monoterpene accumulation in grape

Disease-Modifying Drugs for Multiple Sclerosis and Association With Survival

BACKGROUND AND OBJECTIVES: We examined the association between the disease-modifying drugs (DMDs) for multiple sclerosis (MS) and survival in a multiregion population-based study. METHODS: We accessed multiple administrative health databases from 4 Canadian provinces. Persons with MS were identified and followed from the most recent of the first MS or demyelinating event or January 1, 1996 (index date), until death, emigration, or December 31, 2017. Association between the first-generation and second-generation DMDs and all-cause mortality was examined using stratified Cox proportional hazard models, reported as adjusted hazard ratios (aHRs). Timing of DMD initiation was explored, with findings reported at 2, 5, or 10 years postindex date, representing very early, early, or late initiation. RESULTS: We identified 35,894 persons with MS; 72% were female. The mean age at index date was 44.5 years (SD = 13.6). The total person-years of follow-up while DMD-exposed was 89,180, and total person-years while unexposed was 342,217. Compared with no exposure, exposure to any DMD or to any first-generation DMD was associated with a 26% lower hazard of mortality (both aHRs 0.74; 95% CI 0.56-0.98), while any second-generation DMD exposure was associated with a 33% lower hazard (aHR 0.67; 95% CI 0.46-0.98). Earlier DMD initiation (beta-interferon or glatiramer acetate vs no exposure) was associated with a significant mortality effect (p < 0.05), while later initiation was not (95% CIs included 1). However, the survival advantage with earlier initiation diminished over time, no longer reaching statistical significance at 15 years postindex date. DISCUSSION: Our study demonstrates an association between the DMDs for MS and improved survival in the real-world setting

Disease-modifying drugs for multiple sclerosis and subsequent health service use

OBJECTIVE: We assessed the relationship between the multiple sclerosis (MS) disease-modifying drugs (DMDs) and healthcare use. METHODS: Persons with MS (aged ⩾18 years) were identified using linked population-based health administrative data in four Canadian provinces and were followed from the most recent of their first MS/demyelinating event or 1 January 1996 until the earliest of death, emigration, or study end (31 December 2017 or 31 March 2018). Prescription records captured DMD exposure, examined as any DMD, then by generation (first-generation (the injectables) or second-generation (orals/infusions)) and individual DMD. The associations with subsequent all-cause hospitalizations and physician visits were examined using proportional means model and negative binomial regression. RESULTS: Of 35,894 MS cases (72% female), mean follow-up was 12.0 years, with person-years of DMD exposure for any, or any first- or second-generation DMD being 63,290, 54,605 and 8685, respectively. Any DMD or any first-generation DMD exposure (versus non-exposure) was associated with a 24% lower hazard of hospitalization (adjusted hazard ratio, aHR: 0.76; 95% confidence intervals (CIs): 0.71–0.82), rising to 29% for the second-generation DMDs (aHR: 0.71; 95% CI: 0.58–0.88). This ranged from 18% for teriflunomide (aHR: 0.82; 95% CI: 0.67–1.00) to 44% for fingolimod (aHR: 0.56; 95% CI: 0.36–0.87). In contrast, DMD exposure was generally not associated with substantial differences in physician visits. CONCLUSION: Findings provide real-world evidence of a beneficial relationship between DMD exposure and hospitalizations

Disease-Modifying Drug Uptake and Health Service Use in the Ageing MS Population

Background: Evidence regarding the efficacy or effectiveness of the disease-modifying drugs (DMDs) in the older multiple sclerosis (MS) population is scarce. This has contributed to a lack of evidence-based treatment recommendations for the ageing MS population in practice guidelines. We examined the relationship between age (<55 and ≥55 years), DMD exposure and health service use in the MS population. Methods: We conducted a population-based observational study using linked administrative health data from British Columbia, Canada. We selected all persons with MS and followed from the most recent of their first MS or demyelinating event, 18th birthday or 01-January-1996 (index date) until the earliest of emigration, death or 31-December-2017 (study end). We assessed DMD exposure status over time, initially as any versus no DMD, then by generation (first or second) and finally by each individual DMD. Age-specific analyses were conducted with all-cause hospitalizations and number of physician visits assessed using proportional means model and negative binomial regression with generalized estimating equations. Results: We included 19,360 persons with MS (72% were women); 10,741/19,360 (56%) had ever reached their 55th birthday. Person-years of follow-up whilst aged <55 was 132,283, and 93,594 whilst aged ≥55. Any DMD, versus no DMD in the <55-year-olds was associated with a 23% lower hazard of hospitalization (adjusted hazard ratio, aHR0.77; 95%CI 0.72-0.82), but not in the ≥55-year-olds (aHR0.95; 95%CI 0.87-1.04). Similar patterns were observed for the first and second generation DMDs. Exposure to any (versus no) DMD was not associated with rates of physician visits in either age group (<55 years: adjusted rate ratio, aRR1.02; 95%CI 1.00-1.04 and ≥55 years: aRR1.00; 95%CI 0.96-1.03), but variation in aRR was observed across the individual DMDs. Conclusion: Our study showed beneficial effects of the DMDs used to treat MS on hospitalizations for those aged <55 at the time of exposure. In contrast, for individuals ≥55 years of age exposed to a DMD, the hazard of hospitalization was not significantly lowered. Our study contributes to the broader understanding of the potential benefits and risks of DMD use in the ageing MS population

Natural disasters, economic growth and sustainable development in China: an empirical study using provincial panel data

Using a newly developed integrated indicator system with entropy weighting, we analyzed the panel data of 577 recorded disasters in 30 provinces of China from 1985–2011 to identify their links with the subsequent economic growth. Meteorological disasters promote economic growth through human capital instead of physical capital. Geological disasters did not trigger local economic growth from 1999–2011. Generally, natural disasters overall had no significant impact on economic growth from 1985–1998. Thus, human capital reinvestment should be the aim in managing recoveries, and it should be used to regenerate the local economy based on long-term sustainable development

A Feasibility Study for CODE-MI: High-Sensitivity Cardiac Troponin - Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women.

Objectives This feasibility study was conducted to inform the design and power evaluation of CODE-MI, a pan-Canadian trial evaluating the impact of using the female-specific 99th-percentile threshold for high-sensitivity cardiac troponin (hs-cTn) on the diagnosis, treatment and outcomes of women presenting to the emergency department with symptoms suggestive for myocardial ischemia. Approach CODE-MI is a multi-center, stepped-wedge cluster randomized trial. The cohort and outcomes will be obtained from routinely collected administrative data. Using linked administrative data from 11 hospitals in Ontario from 2014/10 to 2017/09, this feasibility study obtained the following estimates: number of eligible patients, i.e., women presenting to the emergency department with symptoms suggestive of myocardial ischemia and a 24-hour peak hs-cTn value within the female-specific and overall thresholds (i.e. primary cohort); the rate of the 1-year composite outcome of all-cause mortality, re-admission for non-fatal myocardial infarction, incident heart failure, or emergent/urgent coronary revascularization. Study power was evaluated via simulations. Results Overall, 2,073,849 emergency department visits were assessed. Among women, chest pain (with or without cardiac features) and shortness of breath were the most common complaints associated with a diagnosis of acute coronary syndrome. An estimated 7.7% of women with these complaints are eligible for inclusion in the primary cohort. The rate of the 1-year outcome in the primary cohort varied significantly across hospitals with a median rate of 12.2% (95%CI: 7.9%-17.7%). With 30 hospitals, randomized at 5-month intervals in 5 steps, approximately 19,600 women are expected to be included in CODE-MI, resulting in >82% power to detect a 20% decrease in the odds of the primary outcome at a 0.05 significance level. Conclusion Routinely collected administrative health data serve as a rich and essential resource for conducting pragmatic trials assessing process change, such as CODE-MI. We demonstrated the strength of using linked administrative health data to guide the design of pragmatic clinical trials and accurately evaluate the study power

The reliability of colorimetry is precise(ly) as expected.

Figure S6. Gene ontology (GO) analysis of the differentially expressed genes between C1 and C2. (JPG 403 kb

Regional variation in hemoglobin distribution among individuals with chronic kidney disease: the ISN International Network of Chronic Kidney Disease (iNET-CKD) Cohorts

Introduction: Despite recognized geographic and sex-based differences in hemoglobin in the general population, these factors are typically ignored in patients with chronic kidney disease (CKD) in whom a single therapeutic range for hemoglobin is recommended. We sought to compare the distribution of hemoglobin across international nondialysis CKD populations and evaluate predictors of hemoglobin.Methods: In this cross-sectional study, hemoglobin distribution was evaluated in each cohort overall and stratified by sex and estimated glomerular filtration rate (eGFR). Relationships between candidate predictors and hemoglobin were assessed from linear regression models in each cohort. Estimates were subsequently pooled in a random effects model.Results: A total of 58,613 participants from 21 adult cohorts (median eGFR range of 17–49 ml/min) and 3 pediatric cohorts (median eGFR range of 26–45 ml/min) were included with broad geographic representation. Hemoglobin values varied substantially among the cohorts, overall and within eGFR categories, with particularly low mean hemoglobin observed in women from Asian and African cohorts. Across the eGFR range, women had a lower hemoglobin compared to men, even at an eGFR of 15 ml/min (mean difference 5.3 g/l, 95% confidence interval [CI] 3.7–6.9). Lower eGFR, female sex, older age, lower body mass index, and diabetic kidney disease were all independent predictors of a lower hemoglobin value; however, this only explained a minority of variance (R2 7%–44% across cohorts).Conclusion: There are substantial regional differences in hemoglobin distribution among individuals with CKD, and the majority of variance is unexplained by demographics, eGFR, or comorbidities. These findings call for a renewed interest in improving our understanding of hemoglobin determinants in specific CKD populations.</p