Chromosomal diversification and karyotype evolution of diploids in the cytologically diverse genus Prospero (Hyacinthaceae)

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Temporal origins and diversification of Artemisia and allies (Anthemideae, Asteraceae)

Temporal origins and diversification of Artemisia and allies (Anthemideae, Asteraceae).- To assess temporal origins and diversification of lineages within subtribe Artemisiinae and Artemisia group a penalized likelihood analysis was applied on nrDNA ITS and ETS of 63 representatives. The tree was calibrated at the stem node of the Kaschgaria/ Artemisia lineage with the most reliable early Artemisia fossil pollen record from Late Oligocene (23 Ma). The results from this study suggest that the origin of the subtribe goes back to the Late Oligocene (24.6 ± 2.6 Ma) whilst the onset of differentiation of the genus Artemisia and most closely related genera is dated to the Early Miocene (19.8 ± 2.3 Ma). Divergence ages for lineages within the Artemisia group are often between the Early and Middle Miocene, whereas their radiations mostly occurred in the Late Miocene and Pliocene. The temporal context was also used to examine biogeographic and morphological (capitula and pollen type) evolution. Within the Artemisia group all lineages except the North American endemic have colonized the Mediterranean Basin at different epochs from Asian ancestors. Our analyses suggest the divergence of the North American endemic group from Asian ancestors (10.8 ± 1.5 Ma) in the Late Miocene. Homogamous-discoid capitula, characteristic of subgenera Seriphidium and Tridentatae, evolved not only in different geographic regions, but also at different times (2.0 ± 0.8 Ma and 7.9 ± 0.9 Ma respectively) within the Artemisia group. The loss of fertility of central flowers of disciform capitula should be considered as an ancient event in the genus since subgenus Dracunculus is one of the first groups that diverged (17.6 ± 2.1 Ma)

First-Line First? Trends in Thiazide Prescribing for Hypertensive Seniors

BACKGROUND: Evidence of reduced cardiovascular morbidity and mortality as well as cost support thiazide diuretics as the first-line choice for treatment of hypertension. The purpose of this study was to determine the proportion of senior hypertensives that received thiazide diuretics as first-line treatment, and to determine if cardiovascular and other potentially relevant comorbidities predict the choice of first-line therapy. METHODS AND FINDINGS: British Columbia PharmaCare data were used to determine the cohort of seniors (residents aged 65 or older) who received their first reimbursed hypertension drug during the period 1993 to 2000. These individual records were linked to medical and hospital claims data using the British Columbia Linked Health Database to find the subset that had diagnoses indicating the presence of hypertension as well as cardiovascular and other relevant comorbidities. Rates of first-line thiazide prescribing as proportion of all first-line treatment were analysed, accounting for patient age, sex, overall clinical complexity, and potentially relevant comorbidities. For the period 1993 to 2000, 82,824 seniors who had diagnoses of hypertension were identified as new users of hypertension drugs. The overall rate at which thiazides were used as first-line treatment varied from 38% among senior hypertensives without any potentially relevant comorbidity to 9% among hypertensives with previous acute myocardial infarction. The rate of first-line thiazide diuretic prescribing for patients with and without potentially relevant comorbidities increased over the study period. Women were more likely than men, and older patients were more likely than younger, to receive first-line thiazide therapy. CONCLUSIONS: Findings indicate that first-line prescribing practices for hypertension are not consistent with the evidence from randomized control trials measuring morbidity and mortality. The health and financial cost of not selecting the most effective and least costly therapeutic options are significant

The KB paradigm and its application to interactive configuration

The knowledge base paradigm aims to express domain knowledge in a rich formal language, and to use this domain knowledge as a knowledge base to solve various problems and tasks that arise in the domain by applying multiple forms of inference. As such, the paradigm applies a strict separation of concerns between information and problem solving. In this paper, we analyze the principles and feasibility of the knowledge base paradigm in the context of an important class of applications: interactive configuration problems. In interactive configuration problems, a configuration of interrelated objects under constraints is searched, where the system assists the user in reaching an intended configuration. It is widely recognized in industry that good software solutions for these problems are very difficult to develop. We investigate such problems from the perspective of the KB paradigm. We show that multiple functionalities in this domain can be achieved by applying different forms of logical inferences on a formal specification of the configuration domain. We report on a proof of concept of this approach in a real-life application with a banking company. To appear in Theory and Practice of Logic Programming (TPLP).Comment: To appear in Theory and Practice of Logic Programming (TPLP

No evidence for a role of competitive capabilities of adults in causing habitat segregation of diploid and hexaploid Senecio carniolicus (Asteracaeae)

Hexaploid individuals of Senecio carniolicus (Asteraceae) predominantly occur in dense swards while diploids prevail in open vegetation. We test whether this habitat segregation is due to differential responses to competition. Linear regression models were used to relate biomass and maximum leaf length of adults to vegetation cover within radii of 20 cm around target individuals. Biomass differed between ploidy levels, but was independent from vegetation cover in both cytotypes. Maximum leaf length of diploids increased with vegetation cover, but remained constant in hexaploids. This suggests that at the adult stage diploids respond to increasing competition by changes in plant architecture rather than changes in resource utilization, while hexaploids are unaffected by competition. Consequently, other factors, such as competitive interactions at earlier life stages, likely are responsible for habitat segregation of diploid and hexaploid S. carniolicus

Patient socioeconomic determinants for the choice of the cheapest molecule within a cluster: evidence from Belgian prescription data

Reference pricing is a common cost-sharing mechanism, with the financial penalty for the use of costly drugs shifted from the third-party payer to the patient. Unintended distributional consequences might arise, if the weakest socioeconomic groups face a relatively higher financial burden. This study analyzed for a sample of Belgian individual prescription data for 4 clusters of commonly used drugs (proton pump inhibitors, statins and two groups of antihypertensives [drugs acting on renin-angiotensin system and dihydropyridine derivatives]) whether the probability to receive the least expensive molecule within a cluster was linked to the socioeconomic status of the patient. Logistic regression models included individual demographic, working, chronic illness and financial status and small area education data for 906,543 prescriptions from 1,280 prescribing general practitioners and specialists. For the 4 clusters, results show that patients with lower socioeconomic status consistently use slightly more the least expensive drugs than other patients. Larger effects are observed for patients residing in a nursing home for the elderly, patients entitled to increased reimbursement of co-payments, unemployed, patients treated in a primary care center financed per capita (and not fee-for-service) and patients having a chronic illness. Also, patients residing in neighborhoods with low education status use more less expensive drugs. The findings of the study suggest that although equity considerations were not explicitly taken into account in the design of the reference price system, there is no real equity problem, as the costly drugs with supplement are not prescribed more often in patients from lower socioeconomic classes

Next-generation sequencing reveals the impact of repetitive DNA in phylogenetically closely related genomes of Orobanchaceae

We used next-generation sequencing to characterize the genomes of nine species of Orobanchaceae of known phylogenetic relationships, different life forms, and including a polyploid species. The study species are the autotrophic, nonparasitic Lindenbergia philippensis, the hemiparasitic Schwalbea americana, and seven nonphotosynthetic parasitic species of Orobanche (Orobanche crenata, Orobanche cumana, Orobanche gracilis (tetraploid), and Orobanche pancicii) and Phelipanche (Phelipanche lavandulacea, Phelipanche purpurea, and Phelipanche ramosa). Ty3/Gypsy elements comprise 1.93%–28.34% of the nine genomes and Ty1/Copia elements comprise 8.09%–22.83%. When compared with L. philippensis and S. americana, the nonphotosynthetic species contain higher proportions of repetitive DNA sequences, perhaps reflecting relaxed selection on genome size in parasitic organisms. Among the parasitic species, those in the genus Orobanche have smaller genomes but higher proportions of repetitive DNA than those in Phelipanche, mostly due to a diversification of repeats and an accumulation of Ty3/ Gypsy elements. Genome downsizing in the tetraploid O. gracilis probably led to sequence loss across most repeat types

Phase 1 dose escalation study of the allosteric AKT inhibitor BAY 1125976 in advanced solid cancer-Lack of association between activating AKT mutation and AKT inhibition-derived efficacy

This open-label, phase I first-in-human study (NCT01915576) of BAY 1125976, a highly specific and potent allosteric inhibitor of AKT1/2, aimed to evaluate the safety, pharmacokinetics, and maximum tolerated dose of BAY 1125976 in patients with advanced solid tumors. Oral dose escalation was investigated with a continuous once daily (QD) treatment (21 days/cycle) and a twice daily (BID) schedule. A dose expansion in 28 patients with hormone receptor-positive metastatic breast cancer, including nine patients harboring th