Phylogeny and systematics of the "Pronophila clade," with 2 new genera to resolve the formerly polyphyletic genus Pseudomaniola (Lepidoptera: Nymphalidae: Satyrinae)

Analysis of a target enrichment molecular dataset confirms the monophyly of the Neotropical montane butterfly group known as the Pronophila Westwood clade, 1 of 2 major lineages of the satyrine subtribe Pronophilina. The Pronophila clade comprises 18-20 recognized genera and some 125 species. Within this group, the genus Pseudomaniola Röber appears as paraphyletic, and is split here into 3 genera, Pseudomaniola sensu novum with 6 species, including 4 previously considered as subspecies of P. phaselis (Hewitson), the monobasic Fahraeusia Pyrcz n. gen. for Catargynnis asuba Thieme, n. comb., and Boyeriana Pyrcz, Espeland & Willmott n. gen., with 9 species. The adults of all 3 genera can be recognized by their wing color patterns, but the strongest synapomorphies are found in the genitalia, especially those of the male, supporting the above systematic de cisions. Notable differences are also found in scale organization and morphology. A divergence time analysis suggests that Fahraeusia diverged from Pseudomaniola + Boyeriana in the mid-Miocene, around 12 Mya, and the subsequent separation of the last 2 genera occurred at the start of the Pliocene at around 5 Mya

Expression and prognostic impact of lncRNAs in acute myeloid leukemia

Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides, located within the intergenic stretches or overlapping antisense transcripts of protein coding genes. LncRNAs are involved in numerous biological roles including imprinting, epigenetic regulation, apoptosis, and cell cycle. To determine whether lncRNAs are associated with clinical features and recurrent mutations in older patients (aged \u3e/=60 y) with cytogenetically normal (CN) acute myeloid leukemia (AML), we evaluated lncRNA expression in 148 untreated older CN-AML cases using a custom microarray platform. An independent set of 71 untreated older patients with CN-AML was used to validate the outcome scores using RNA sequencing. Distinctive lncRNA profiles were found associated with selected mutations, such as internal tandem duplications in the FLT3 gene (FLT3-ITD) and mutations in the NPM1, CEBPA, IDH2, ASXL1, and RUNX1 genes. Using the lncRNAs most associated with event-free survival in a training cohort of 148 older patients with CN-AML, we derived a lncRNA score composed of 48 lncRNAs. Patients with an unfavorable compared with favorable lncRNA score had a lower complete response (CR) rate [P \u3c 0.001, odds ratio = 0.14, 54% vs. 89%], shorter disease-free survival (DFS) [P \u3c 0.001, hazard ratio (HR) = 2.88] and overall survival (OS) (P \u3c 0.001, HR = 2.95). The validation set analyses confirmed these results (CR, P = 0.03; DFS, P = 0.009; OS, P = 0.009). Multivariable analyses for CR, DFS, and OS identified the lncRNA score as an independent marker for outcome. In conclusion, lncRNA expression in AML is closely associated with recurrent mutations. A small subset of lncRNAs is correlated strongly with treatment response and survival

Homological computation using spanning trees

We introduce here a new F2 homology computation algorithm based on a generalization of the spanning tree technique on a finite 3-dimensional cell complex K embedded in ℝ3. We demonstrate that the complexity of this algorithm is linear in the number of cells. In fact, this process computes an algebraic map φ over K, called homology gradient vector field (HGVF), from which it is possible to infer in a straightforward manner homological information like Euler characteristic, relative homology groups, representative cycles for homology generators, topological skeletons, Reeb graphs, cohomology algebra, higher (co)homology operations, etc. This process can be generalized to others coefficients, including the integers, and to higher dimension

Leaky ryanodine receptors contribute to diaphragmatic weakness during mechanical ventilation

Ventilator-induced diaphragmatic dysfunction (VIDD) refers to the diaphragm muscle weakness that occurs following prolonged controlled mechanical ventilation (MV). The presence of VIDD impedes recovery from respiratory failure. However, the pathophysiological mechanisms accounting for VIDD are still not fully understood. Here, we show in human subjects and a mouse model of VIDD that MV is associated with rapid remodeling of the sarcoplasmic reticulum (SR) Ca2+ release channel/ryanodine receptor (RyR1) in the diaphragm. The RyR1 macromolecular complex was oxidized, S-nitrosylated, Ser-2844 phosphorylated, and depleted of the stabilizing subunit calstabin1, following MV. These posttranslational modifications of RyR1 were mediated by both oxidative stress mediated by MV and stimulation of adrenergic signaling resulting from the anesthesia. We demonstrate in the murine model that such abnormal resting SR Ca2+ leak resulted in reduced contractile function and muscle fiber atrophy for longer duration of MV. Treatment with β-adrenergic antagonists or with S107, a small molecule drug that stabilizes the RyR1–calstabin1 interaction, prevented VIDD. Diaphragmatic dysfunction is common in MV patients and is a major cause of failure to wean patients from ventilator support. This study provides the first evidence to our knowledge of RyR1 alterations as a proximal mechanism underlying VIDD (i.e., loss of function, muscle atrophy) and identifies RyR1 as a potential target for therapeutic intervention

Is three the magic number? The role of ergonomic principles in cross country comprehension of road traffic signs

Road sign comprehension plays an important part in road safety management, particularly for those drivers who are travelling in an unfamiliar country. Previous research has established that comprehension can be improved if signs are designed to adhere to ergonomic principles. However, it may be difficult for sign designers to incorporate all the principles into a single sign and may thus have to make a judgement as to the most effective ones. This study surveyed drivers in three countries to ascertain their understanding of a range of road signs, each of which conformed in varying degrees and combinations to the ergonomic principles. We found that using three of the principles was the most effective and that the most important one was that relating to standardisation; the colours and shapes used were key to comprehension. Other concepts which related to physical and spatial characteristics were less important, whilst conceptual compatibility did not aid comprehension at all. Practitioner Summary: This study explores how road sign comprehension can be improved using ergonomic principles, with particular reference to cross-border drivers. It was found that comprehension can be improved significantly if standardisation is adhered to and if at least three principles are used

Global 3-D Simulations of the Triple Oxygen Isotope Signature Δ17O in Atmospheric CO2

The triple oxygen isotope signature Δ¹⁷O in atmospheric CO₂, also known as its “¹⁷O excess,” has been proposed as a tracer for gross primary production (the gross uptake of CO₂ by vegetation through photosynthesis). We present the first global 3-D model simulations for Δ¹⁷O in atmospheric CO₂ together with a detailed model description and sensitivity analyses. In our 3-D model framework we include the stratospheric source of Δ¹⁷O in CO₂ and the surface sinks from vegetation, soils, ocean, biomass burning, and fossil fuel combustion. The effect of oxidation of atmospheric CO on Δ¹⁷O in CO2 is also included in our model. We estimate that the global mean Δ¹⁷O (defined as Δ¹⁷O = ln( ¹⁷O + 1) − RL · ln( ¹⁸O + 1) with RL = 0.5229) of CO₂ in the lowest 500 m of the atmosphere is 39.6 per meg, which is ∼20 per meg lower than estimates from existing box models. We compare our model results with a measured stratospheric Δ¹⁷O in CO₂ profile from Sodankylä (Finland), which shows good agreement. In addition, we compare our model results with tropospheric measurements of Δ¹⁷O in CO₂ from Göttingen (Germany) and Taipei (Taiwan), which shows some agreement but we also find substantial discrepancies that are subsequently discussed. Finally, we show model results for Zotino (Russia), Mauna Loa (United States), Manaus (Brazil), and South Pole, which we propose as possible locations for future measurements of Δ¹⁷O in tropospheric CO₂ that can help to further increase our understanding of the global budget of Δ¹⁷O in atmospheric CO₂

The value of health

<p>Abstract</p> <p>Background</p> <p>A major problem in cost-effectiveness studies is where to draw the line between interventions which are cost-effective and those who are not. Lacking a notion about the value of a QALY, all ultimate values to the cost-effectiveness ratio are essentially arbitrary.</p> <p>Methods</p> <p>This paper presents a simple empirical model to estimate the compensating income variation of diseases and health problems. The model is estimated using data for the Netherlands.</p> <p>Results</p> <p>The compensating income variation is between €20,000 and €90,000. This is higher than most of the ultimate values used by policy-makers to decide whether an intervention is cost-effective. Our figures are roughly similar to those found in studies about the value of a statistical life year.</p> <p>Conclusion</p> <p>Estimates on the compensating income variation of diseases and health problems may provide useful information on the maximum acceptable cost-effectiveness ratio of medical interventions than those currently used by policy makers.</p

Plasma sRAGE is independently associated with increased mortality in ARDS: a meta-analysis of individual patient data

The soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury and alveolar fluid clearance (AFC), with promising values for assessing prognosis and lung injury severity in acute respiratory distress syndrome (ARDS). Because AFC is impaired in most patients with ARDS and is associated with higher mortality, we hypothesized that baseline plasma sRAGE would predict mortality, independently of two key mediators of ventilator-induced lung injury. We conducted a meta-analysis of individual data from 746 patients enrolled in eight prospective randomized and observational studies in which plasma sRAGE was measured in ARDS articles published through March 2016. The primary outcome was 90-day mortality. Using multivariate and mediation analyses, we tested the association between baseline plasma sRAGE and mortality, independently of driving pressure and tidal volume. Higher baseline plasma sRAGE [odds ratio (OR) for each one-log increment, 1.18; 95% confidence interval (CI) 1.01-1.38; P = 0.04], driving pressure (OR for each one-point increment, 1.04; 95% CI 1.02-1.07; P = 0.002), and tidal volume (OR for each one-log increment, 1.98; 95% CI 1.07-3.64; P = 0.03) were independently associated with higher 90-day mortality in multivariate analysis. Baseline plasma sRAGE mediated a small fraction of the effect of higher Delta P on mortality but not that of higher V (T). Higher baseline plasma sRAGE was associated with higher 90-day mortality in patients with ARDS, independently of driving pressure and tidal volume, thus reinforcing the likely contribution of alveolar epithelial injury as an important prognostic factor in ARDS. Registration: PROSPERO (ID: CRD42018100241)