Callus culture development of two varieties of Tagetes erecta and carotenoid production

Background: The properties of natural pigments, such as antioxidants, functional,medical, and nutraceutical, have demonstrated the advantages of these natural compounds over synthetic ones. Some products are accepted only when they are pigmented with natural, food-quality colorants: for example poultry products (manly marigold flower extracts). Carotenoids such as \u3b2-carotene, \u3b2-criptoxanthin and lutein are very attractive as natural food colorants due to their antioxidant and pro-vitamin activities which provide additional value to the target products. Marigold ( Tagetes erecta ) is an Asteraceous ornamental plant native to Mexico, and it is also important as a carotenoid source for industrial and medicinal purposes but nowadays its production is destined mainly for ornamental purposes. Results: Friable callus of T. erecta yellow flower (YF) and white flower (WF) varieties was induced from leaf explants on Murashige and Skoog (MS) medium supplemented with 9.0 \u3bcM 4-dichlorophenoxyacetic acid (2,4-D) and 8.8 \u3bcM benzyladenine (BA). Calluses developed from both varieties were different in pigmentation. Extract characterization from callus cultures was carried out by high-performance liquid chromatography (HPLC). This analytical process detected several carotenoids; the main pigments in extracts from YF callus were lutein and zeaxanthin, whereas in the extracts of the WF callus the main pigmentswere lutein, zeaxanthin, \u3b2-cryptoxanthin and \u3b2-carotene. Callus cultures of T. erecta accumulated pigments even after several rounds of subculture. Conclusions: WF callus appeared to be a suitable candidate as a source of different carotenoids, and tested varieties could represent an alternative for further studies about in vitro pigment production

Ionize Hard: Interstellar PO+ Detection

We report the first detection of the phosphorus monoxide ion (PO+) in the interstellar medium. Our unbiased and very sensitive spectral survey toward the G+0.693–0.027 molecular cloud covers four different rotational transitions of this molecule, two of which (J = 1–0 and J = 2–1) appear free of contamination from other species. The fit performed, assuming local thermodynamic equilibrium conditions, yields a column density of N=(6.0 \ub1 0.7) 7 1011\ua0cm−2. The resulting molecular abundance with respect to molecular hydrogen is 4.5 7 10–12. The column density of PO+ normalized by the cosmic abundance of P is larger than those of NO+ and SO+, normalized by N and S, by factors of 3.6 and 2.3, respectively. The N(PO+)/N(PO) ratio is 0.12 \ub1 0.03, more than one order of magnitude higher than that of N(SO+)/N(SO) and N(NO+)/N(NO). These results indicate that P is more efficiently ionized than N and S in the ISM. We have performed new chemical models that confirm that the PO+ abundance is strongly enhanced in shocked regions with high values of cosmic-ray ionization rates (10–15 − 10–14 s−1), as occurring in the G+0.693–0.027 molecular cloud. The shocks sputter the interstellar icy grain mantles, releasing into the gas phase most of their P content, mainly in the form of PH3, which is converted into atomic P, and then ionized efficiently by cosmic rays, forming P+. Further reactions with O2 and OH produces PO+. The cosmic-ray ionization of PO might also contribute significantly, which would explain the high N(PO+)/N(PO) ratio observed. The relatively high gas-phase abundance of PO+ with respect to other P-bearing species stresses the relevance of this species in the interstellar chemistry of P

Long-term effects of evolocumab in participants with HIV and dyslipidemia: results from the open-label extension period

Objectives: People with HIV (PWH) are at an increased risk of atherosclerotic cardiovascular disease. Suboptimal responses to statin therapy in PWH may result from antiretroviral therapies (ARTs). This open-label extension study aimed to evaluate the long-term safety and efficacy of evolocumab up to 52\u200aweeks in PWH. Design: This final analysis of a multinational, placebo-controlled, double-blind, randomized phase 3 trial evaluated the effect of monthly subcutaneous evolocumab 420\u200amg on low-density lipoprotein cholesterol (LDL-C) during the open-label period (OLP) following 24\u200aweeks of double-blind period in PWH with hypercholesterolemia/mixed dyslipidemia. All participants enrolled had elevated LDL-C or nonhigh-density lipoprotein cholesterol (non-HDL-C) and were on stable maximally tolerated statin and stable ART. Methods: Efficacy was assessed by percentage change from baseline in LDL-C, triglycerides, and atherogenic lipoproteins. Treatment-emergent adverse events (TEAEs) were examined. Results: Of the 467 participants randomized in the double-blind period, 451 (96.6%) received at least one dose of evolocumab during the OLP (mean age of 56.4\u200ayears, 82.5% male, mean duration with HIV of 17.4\u200ayears). By the end of the 52-week OLP, the overall mean (SD) percentage change in LDL-C from baseline was -57.8% (22.8%). Evolocumab also reduced triglycerides, atherogenic lipid parameters (non-HDL-C, apolipoprotein B, total cholesterol, very-low-density lipoprotein cholesterol, and lipoprotein[a]), and increased HDL-C. TEAEs were similar between placebo and evolocumab during the OLP. Conclusion: Long-term administration of evolocumab lowered LDL-C and non-HDL-C, allowing more PWH to achieve recommended lipid goals with no serious adverse events. Trail registration: NCT02833844. Video abstract: http://links.lww.com/QAD/C441

Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49\ub74% (95% uncertainty interval [UI] 46\ub74–52\ub70). The TFR decreased from 4\ub77 livebirths (4\ub75–4\ub79) to 2\ub74 livebirths (2\ub72–2\ub75), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83\ub78 million people per year since 1985. The global population increased by 197\ub72% (193\ub73–200\ub78) since 1950, from 2\ub76 billion (2\ub75–2\ub76) to 7\ub76 billion (7\ub74–7\ub79) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2\ub70%; this rate then remained nearly constant until 1970 and then decreased to 1\ub71% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2\ub75% in 1963 to 0\ub77% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2\ub77%. The global average age increased from 26\ub76 years in 1950 to 32\ub71 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59\ub79% to 65\ub73%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1\ub70 livebirths (95% UI 0\ub79–1\ub72) in Cyprus to a high of 7\ub71 livebirths (6\ub78–7\ub74) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0\ub708 livebirths (0\ub707–0\ub709) in South Korea to 2\ub74 livebirths (2\ub72–2\ub76) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0\ub73 livebirths (0\ub73–0\ub74) in Puerto Rico to a high of 3\ub71 livebirths (3\ub70–3\ub72) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2\ub70% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Percentile values of the standing broad jump in children and adolescents aged 6-18 years old

The standing broad jump (SBJ) is a valid, reliable and feasible field-based test, which can evaluate explosive strength of the lower limbs and physical fitness. This study aimed to provide normative data for the SBJ for male and female children and adolescents and describe differences in performance between age groups and genders. A total number of 2140 children and adolescents, sampled in seven European nations have been included for analysis. The SBJ was performed to derive percentile values for gender and each age group. In general, males have greater jumping performance compared to females. Data demonstrate a linear increase in the jumping distance for both males and females until adolescence. However, such increase is evident in males up to 16-17 years old, whereas in females a plateau value is met at 12-13 years old, with a subsequent decrease in the jumping performance. No differences were present in jumping performance between male and female children, however differences between male and female adolescents were evinced. The study has provided percentile values useful to monitor the physical fitness status of children and adolescents

More at stake in stem-cell patents

Austin Smith and others argue in favour of patenting technologies derived from human embryonic stem cells (Nature 472, 418; 2011), a case still pending with the European Court of Justice. But there is more at stake than European commercial interests. In 1998, agreement was reached in Europe under Directive 98/44 not to recognize patents involving the use of human embryos for commercial purposes (R. Hipp and P. Liese Nature 474, 36; 2011). The court must decide whether the use of these cells \u2018necessitates the prior destruction of human embryos or their use as base material\u2019, as the advocategeneral, Yves Bot, has argued (see go.nature.com/gsap8n). If so, such use would seem to fall beyond the scope of what is legally patentable. Smith et al. warn that \u201cEuropean discoveries could be translated into applications elsewhere, at a potential cost to the European citizen.\u201d This begs the question of whether patents, which may also be held by non-European companies, may sometimes impede wider research cooperation (S. Rabin Nature Biotechnol. 23, 817\u2013819; 2005). In any case there will often be some commercial risk whenever Europe defends a more rigorous ethical standard than is defended elsewhere. This risk is not itself an argument against upholding the standard prescribed by law. Without prejudice to the final judgment in this case, the resolution of patent law is and ought to be more than a question of European commercial interest

Daily dataset of 20th century surface air temperature and precipitation series for the European Climate Assessment

We present a dataset of daily resolution climatic time series that has been compiled for the European Climate Assessment (ECA). As of December 2001, this ECA dataset comprises 199 series of minimum, maximum and/or daily mean temperature and 195 series of daily precipitation amount observed at meteorological stations in Europe and the Middle East. Almost all series cover the standard normal period 1961-90, and about 50% extends back to at least 1925. Part of the dataset (90%) is made available for climate research on CDROM and through the Internet (at http://www.knmi.nl/samenw/eca). A comparison of the ECA dataset with existing gridded datasets, having monthly resolution, shows that correlation coefficients between ECA stations and nearest land grid boxes between 1946 and 1999 are higher than 0.8 for 93% of the temperature series and for 51% of the precipitation series. The overall trends in the ECA dataset are of comparable magnitude to those in the gridded datasets. The potential of the ECA dataset for climate studies is demonstrated in two examples. In the first example, it is shown that the winter (October-March) warming in Europe in the 1976-99 period is accompanied by a positive trend in the number of warm-spell days at most stations, but not by a negative trend in the number of cold-spell days. Instead, the number of cold-spell days increases over Europe