The interplay between conformation and absolute configuration in chiral electron dynamics of small diols

A competition between chiral characteristics alternatively attributable to either conformation or to absolute configuration is identified. Circular dichroism associated with photoexcitation of the outer orbital of configurational enantiomers of 1,3- and 2,3-butanediols has been examined with a focus on the large changes in electron chiral asymmetry produced by different molecular conformations. Experimental gas phase measurements offer support for the theoretical modelling of this chiroptical effect. A surprising prediction is that a conformationally produced pseudoenantiomerism in 1,3-butanediol generates a chiral response in the frontier electron dynamics that effectively outweighs the influence of the permanent configurational handedness established at the asymmetrically substituted carbon. Induced conformation, and specifically induced conformational chirality, may thus be a dominating factor in chiral molecular recognition in such systems

Modeled Health and Economic Impact of Team-Based Care for Hypertension

IntroductionTeam-based interventions for hypertension care have been widely studied and shown effective in improving hypertension outcomes. Few studies have evaluated long-term effects of these interventions; none have assessed broad-scale implementation. This study estimates the prospective health, economic, and budgetary impact of universal adoption of a team-based care intervention model that targets people with treated but uncontrolled hypertension in the U.S.MethodsAnalysis was conducted in 2014−2015 using a microsimulation model, constructed with various data sources from 1948 to 2014, designed to evaluate prospective cardiovascular disease (CVD)−related interventions in the U.S. population. Ten-year primary outcomes included prevalence of uncontrolled hypertension; incident myocardial infarction, stroke, CVD events, and CVD-related mortality; intervention and net medical costs by payer; productivity; and quality-adjusted life years.ResultsAbout 4.7 million (13%) fewer people with uncontrolled hypertension and 638,000 prevented cardiovascular events would be expected over 10 years. Assuming $525 per enrollee, implementation would cost payers$22.9 billion, but $25.3 billion would be saved in averted medical costs. Estimated net cost savings for Medicare approached$5.8 billion. Net costs were especially sensitive to intervention costs, with break-even thresholds of $300 (private),$450 (Medicaid), and $750 (Medicare).ConclusionsNationwide adoption of team-based care for uncontrolled hypertension could have sizable effects in reducing CVD burden. Based on the study’s assumptions, the policy would be cost saving from the perspective of Medicare and may prove to be cost effective from other payers’ perspectives. Expected net cost savings for Medicare would more than offset expected net costs for all other insurers

High-Throughput Genome-Wide Genotyping To Optimize the Use of Natural Genetic Resources in the Grassland Species Perennial Ryegrass (Lolium perenne L.)

The natural genetic diversity of agricultural species is an essential genetic resource for breeding programs aiming to improve their ecosystem and production services. A large natural ecotype diversity is usually available for most grassland species. This could be used to recombine natural climatic adaptations and agronomic value to create improved populations of grassland species adapted to future regional climates. However describing natural genetic resources can be long and costly. Molecular markers may provide useful information to help this task. This opportunity was investigated for Lolium perenne L., using a set of 385 accessions from the natural diversity of this species collected right across Europe and provided by genebanks of several countries. For each of these populations, genotyping provided the allele frequencies of 189,781 SNP markers. GWAS were implemented for over 30 agronomic and/or putatively adaptive traits recorded in three climatically contrasted locations (France, Belgium, Germany). Significant associations were detected for hundreds of markers despite a strong confounding effect of the genetic background; most of them pertained to phenology traits. It is likely that genetic variability in these traits has had an important contribution to environmental adaptation and ecotype differentiation. Genomic prediction models calibrated using natural diversity were found to be highly effective to describe natural populations for almost all traits as well as commercial synthetic populations for some important traits such as disease resistance, spring growth or phenological traits. These results will certainly be valuable information to help the use of natural genetic resources of other species

Canonical correlations reveal adaptive loci and phenotypic responses to climate in perennial ryegrass

Germplasm from perennial ryegrass (Lolium perenne L.) natural populations is useful for breeding because of its adaptation to a wide range of climates. Climate‐adaptive genes can be detected from associations between genotype, phenotype and climate but an integrated framework for the analysis of these three sources of information is lacking. We used two approaches to identify adaptive loci in perennial ryegrass and their effect on phenotypic traits. First, we combined Genome‐Environment Association (GEA) and GWAS analyses. Then, we implemented a new test based on a Canonical Correlation Analysis (CANCOR) to detect adaptive loci. Furthermore, we improved the previous perennial ryegrass gene set by de novo gene prediction and functional annotation of 39,967 genes. GEA‐GWAS revealed eight outlier loci associated with both environmental variables and phenotypic traits. CANCOR retrieved 633 outlier loci associated with two climatic gradients, characterized by cold‐dry winter versus mild‐wet winter and long rainy season versus long summer, and pointed out traits putatively conferring adaptation at the extremes of these gradients. Our CANCOR test also revealed the presence of both polygenic and oligogenic climatic adaptations. Our gene annotation revealed that 374 of the CANCOR outlier loci were positioned within or close to a gene. Co‐association networks of outlier loci revealed a potential utility of CANCOR for investigating the interaction of genes involved in polygenic adaptations. The CANCOR test provides an integrated framework to analyse adaptive genomic diversity and phenotypic responses to environmental selection pressures that could be used to facilitate the adaptation of plant species to climate change

Pleistocene climate changes, and not agricultural spread, accounts for range expansion and admixture in the dominant grassland species <i>Lolium perenne</i> L.

International audienceAim: Grasslands have been pivotal in the development of herbivore breeding since the Neolithic and still represent the most widespread agricultural land use across Europe. However, it remains unclear whether the current large‐scale genetic variation of plant species found in natural grasslands of Europe is the result of human activities or natural processes. Location: Europe. Taxon: Lolium perenne L. (perennial ryegrass). Methods: We reconstructed the phylogeographic history of L. perenne, a dominant grassland species, using 481 natural populations, including 11 populations of closely related taxa. We combined Genotyping‐by‐Sequencing (GBS) and pool‐Sequencing (pool‐Seq) to obtain high‐quality allele frequency calls of ~500 k SNP loci. We performed genetic structure analyses and demographic reconstructions based on the site frequency spectrum (SFS). We additionally used the same genotyping protocol to assess the genomic diversity of a set of 32 cultivars representative of the L. perenne cultivars widely used for forage purposes. Results: Expansion across Europe took place during the Würm glaciation (12–110 kya), a cooling period that decreased the dominance of trees in favour of grasses. Splits and admixtures in L. perenne fit historical climate changes in the Mediterranean basin. The development of agriculture in Europe (7–3.5 kya), that caused an increase in the abundance of grasslands, did not have an effect on the demographic patterns of L. perenne. We found that most modern cultivars are closely related to natural diversity from north-western Europe. Thus, modern cultivars do not represent the wide genetic variation found in natural populations. Main conclusions: Demographic events in L. perenne can be explained by the changing climatic conditions during the Pleistocene. Natural populations maintain a wide genomic variability at continental scale that has been minimally exploited by recent breeding activities. This variability constitutes valuable standing genetic variation for future adaptation of grasslands to climate change, safeguarding the agricultural services they provide

Integrated information increases with fitness in the evolution of animats

One of the hallmarks of biological organisms is their ability to integrate disparate information sources to optimize their behavior in complex environments. How this capability can be quantified and related to the functional complexity of an organism remains a challenging problem, in particular since organismal functional complexity is not well-defined. We present here several candidate measures that quantify information and integration, and study their dependence on fitness as an artificial agent ("animat") evolves over thousands of generations to solve a navigation task in a simple, simulated environment. We compare the ability of these measures to predict high fitness with more conventional information-theoretic processing measures. As the animat adapts by increasing its "fit" to the world, information integration and processing increase commensurately along the evolutionary line of descent. We suggest that the correlation of fitness with information integration and with processing measures implies that high fitness requires both information processing as well as integration, but that information integration may be a better measure when the task requires memory. A correlation of measures of information integration (but also information processing) and fitness strongly suggests that these measures reflect the functional complexity of the animat, and that such measures can be used to quantify functional complexity even in the absence of fitness data.Comment: 27 pages, 8 figures, one supplementary figure. Three supplementary video files available on request. Version commensurate with published text in PLoS Comput. Bio

ACC/AHA Guidelines for Coronary Angiography. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Coronary Angiography)

"The ACC/AHA Task Force on Practice Guidelines herein revises and updates the original “Guidelines for Coronary Angiography,” published in 1987 (1). The frequent and still-growing use of coronary angiography, its relatively high costs, its inherent risks and the ongoing evolution of its indications have given this revision urgency and priority. The expert committee appointed included private practitioners and academicians. Committee members were selected to represent both experts in coronary angiography and senior clinician consultants. Representatives from the family practice and internal medicine professions were also included on the committee. The English-language medical literature was searched for the 10 years preceding development of the guidelines. The searches yielded >1,600 references that the committee reviewed for relevance. Evidence relative to the use of coronary angiography was compiled and evaluated by the committee. Whereas randomized trials are often available for reference in the development of treatment guidelines, randomized trials regarding the use of diagnostic procedures such as coronary angiography are rarely available (2). For development of these guidelines, when coronary angiography was a necessary procedure in describing a clinical subset or in choosing a course of treatment and that therapy was shown to have an advantage for the patient, especially in the context of a randomized trial, then the indication for angiography was given greater consideration than indications cited in less-rigorous evaluations of data.