Evolutionary history of the buildup and breakdown of the heterostylous syndrome in Plumbaginaceae.

The evolutionary pathways leading to the heterostylous syndrome are not well understood, and models concerning the origins of distyly differ in the order in which reciprocal herkogamy and self-incompatibility evolve. We investigated the evolution and breakdown of distyly in Plumbaginaceae, a family with considerable diversity of floral traits and reproductive systems. Using Bayesian Markov chain Monte Carlo analyses and stochastic character mapping, we examined the evolutionary assembly and breakdown of the heterostylous syndrome based on a well-resolved phylogeny of 121 species of Plumbaginaceae and six outgroup taxa using five nuclear and plastid gene regions. We used the distribution of reproductive traits and reconstructed ancestral characters across phylogenies to evaluate competing models for the evolution of distyly. The most likely common ancestor of Plumbaginaceae was self-incompatible and monomorphic for sex-organ arrangement and pollen-stigma characters. Character state reconstructions indicated that reciprocal herkogamy evolved at least three times and that shifts to selfing and apomixis occurred on multiple occasions. Our results provide comparative support for the early ideas of H. G. Baker on evolutionary pathways in Plumbaginaceae, and the more recent selfing avoidance model by D. & B. Charlesworth in which distyly evolves from self-incompatible ancestors.

Comparison of the new Exponential Injury Severity Score with the Injury Severity Score and the New Injury Severity Score in trauma patients: A cross-sectional study.

OBJECTIVE: To compare Exponential Injury Severity Score (EISS) with Injury Severity Score (ISS) and New Injury Severity Score (NISS) in terms of their predictive capability of the outcomes and medical expenses of hospitalized adult trauma patients. SETTING: This study was based at a level I trauma center in Taiwan. METHODS: Data for 17,855 adult patients hospitalized from January 1, 2009 to December 31, 2015 were retrieved from the Trauma Registry System. The primary outcome was in-hospital mortality. Secondary outcomes were the hospital length of stay (LOS), intensive care unit (ICU) admission rate, ICU LOS, and medical expenses. Chi-square tests were used for categorical variables to determine the significance of the associations between the predictor and outcome variables. Student t-tests were applied to analyze normally distributed data for continuous variables, while Mann-Whitney U tests were used to compare non-normally distributed data. RESULTS: According to the survival rate-to-severity score relationship curve, we grouped all adult trauma patients based on EISS scores of ≥ 27, 9-26, and < 9. Significantly higher mortality rates were noted in patients with EISS ≥ 27 and those with EISS of 9-26 when compared to patients with EISS < 9; this finding concurred to the findings for groups classified by the ISS and NISS with the cut-off points set between 25 and 16. The hospital LOS, ICU admission rates, and medical expenses for patients with EISS ≥ 27 and patients with EISS of 9-26 were also significantly longer and higher than that of patients with EISS < 9. When comparing the demographics and detailed medical expenses of very severely injured adult trauma patients classified according to ISS, NISS, and EISS, patients with ISS ≥ 25 and NISS ≥ 25 both had significantly lower mortality rates, lower ICU admission rates, and shorter ICU LOS compared to patients with EISS ≥ 27. CONCLUSIONS: EISS 9 and 27 can serve as two cut-off points regarding injury severity, and patients with EISS ≥ 27 have the greatest injury severity. Additionally, these patients have the highest mortality rate, the highest ICU admission rate, and the longest ICU LOS compared to those with ISS ≥ 25 and NISS ≥ 25, suggesting that patients with EISS ≥ 27 have the worst outcome.

Biologic therapies for refractory juvenile dermatomyositis: five years of experience of the Childhood Arthritis and Rheumatology Research Alliance in North America.

BACKGROUND: The prognosis of children with juvenile dermatomyositis (JDM) has improved remarkably since the 1960's with the use of corticosteroid and immunosuppressive therapy. Yet there remain a minority of children who have refractory disease. Since 2003 the sporadic use of biologics (genetically-engineered proteins that usually are derived from human genes) for inflammatory myositis has been reported. In 2011-2016 we investigated our collective experience of biologics in JDM through the Childhood Arthritis and Rheumatology Research Alliance (CARRA). METHODS: The JDM biologic study group developed a survey on the CARRA member experience using biologics for Juvenile DM utilizing Delphi consensus methods in 2011-2012. The survey was completed online by the CARRA members interested in JDM in 2012. A second survey was similarly developed that provided more opportunity to describe their experiences with biologics in JDM in detail and was completed by CARRA members in Feb 2013. During three CARRA meetings in 2013-2015, nominal group techniques were used for achieving consensus on the current choices of biologic drugs. A final survey was performed at the 2016 CARRA meeting. RESULTS: One hundred and five of a potential 231 pediatric rheumatologists (42%) responded to the first survey in 2012. Thirty-five of 90 had never used a biologic for Juvenile DM at that time. Fifty-five of 91 (denominators vary) had used biologics for JDM in their practice with 32%, 5%, and 4% using rituximab, etanercept, and infliximab, respectively, and 17% having used more than one of the three drugs. Ten percent used a biologic as monotherapy, 19% a biologic in combination with methotrexate (mtx), 52% a biologic in combination with mtx and corticosteroids, 42% a combination of a biologic, mtx, corticosteroids (steroids), and an immunosuppressive drug, and 43% a combination of a biologic, IVIG and mtx. The results of the second survey supported these findings in considerably more detail with multiple combinations of drugs used with biologics and supported the use of rituximab, abatacept, anti-TNFα drugs, and tocilizumab in that order. One hundred percent recommended that CARRA continue studying biologics for JDM. The CARRA meeting survey in 2016 again supported the study and use of these four biologic drug groups. CONCLUSIONS: Our CARRA JDM biologic work group developed and performed three surveys demonstrating that pediatric rheumatologists in North America have been using multiple biologics for refractory JDM in numerous scenarios from 2011 to 2016. These survey results and our consensus meetings determined our choice of four biologic therapies (rituximab, abatacept, tocilizumab and anti-TNFα drugs) to consider for refractory JDM treatment when indicated and to evaluate for comparative effectiveness and safety in the future. Significance and Innovations This is the first report that provides a substantial clinical experience of a large group of pediatric rheumatologists with biologics for refractory JDM over five years. This experience with biologic therapies for refractory JDM may aid pediatric rheumatologists in the current treatment of these children and form a basis for further clinical research into the comparative effectiveness and safety of biologics for refractory JDM.