Disentangling the formation history of galaxies via population-orbit superposition: Method validation

We present population-orbit superposition models for external galaxies based on Schwarzschild's orbit-superposition method, by tagging the orbits with age and metallicity. The models fit the density distributions, kinematic, and age and metallicity maps from integral field unit (IFU) spectroscopy observations.We validate the method and demonstrate its power by applying it to mock data, similar to those obtained by the Multi-Unit Spectroscopic Explorer (MUSE) IFU on the Very Large Telescope (VLT). These mock data are created from Auriga galaxy simulations, viewed at three different inclination angles (v = 40°, 60°, 80°). Constrained by MUSE-like mock data, our model can recover the galaxy's stellar orbit distribution projected in orbital circularity λz versus radius r, the intrinsic stellar population distribution in age t versus metallicity Z, and the correlation between orbits' circularity λz and stellar age t. A physically motivated age-metallicity relation improves the recovering of intrinsic stellar population distributions. We decompose galaxies into cold, warm, and hot-rotating components based on their orbit circularity distribution, and find that the surface density, velocity, velocity dispersion, and age and metallicity maps of each component from our models well reproduce those from simulation, especially for projections close to edge-on. These galaxies exhibit strong global age versus σz relation, which is well recovered by our model. The method has the power to reveal the detailed build-up of stellar structures in galaxies, and offers a complement to local resolved, and high-redshift studies of galaxy evolution

A Deep View into the Nucleus of the Sagittarius Dwarf Spheroidal Galaxy with MUSE. II. Kinematic Characterization of the Stellar Populations

The Sagittarius dwarf spheroidal galaxy is in an advanced stage of disruption but still hosts its nuclear star cluster (NSC), M54, at its center. In this paper, we present a detailed kinematic characterization of the three stellar populations present in M54: young metal-rich (YMR); intermediate-age metal-rich (IMR); and old metal-poor (OMP), based on the spectra of ~6500 individual M54 member stars extracted from a large Multi-Unit Spectroscopic Explorer (MUSE)/Very Large Telescope data set. We find that the OMP population is slightly flattened with a low amount of rotation (~0.8 km s−1) and with a velocity dispersion that follows a Plummer profile. The YMR population displays a high amount of rotation (~5 km s−1) and a high degree of flattening, with a lower and flat velocity dispersion profile. The IMR population shows a high but flat velocity dispersion profile, with some degree of rotation (~2 km s−1). We complement our MUSE data with information from Gaia DR2 and confirm that the stars from the OMP and YMR populations are comoving in 3D space, suggesting that they are dynamically bound. While dynamical evolutionary effects (e.g., energy equipartition) are able to explain the differences in velocity dispersion between the stellar populations, the strong differences in rotation indicate different formation paths for the populations, as supported by an N-body simulation tailored to emulate the YMR–OMP system. This study provides additional evidence for the M54 formation scenario proposed in our previous work, where this NSC formed via GC accretion (OMP) and in situ formation from gas accretion in a rotationally supported disk (YMR)

Reducing errors in health care: cost-effectiveness of multidisciplinary team training in obstetric emergencies (TOSTI study); a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>There are many avoidable deaths in hospitals because the care team is not well attuned. Training in emergency situations is generally followed on an individual basis. In practice, however, hospital patients are treated by a team composed of various disciplines. To prevent communication errors, it is important to focus the training on the team as a whole, rather than on the individual. Team training appears to be important in contributing toward preventing these errors. Obstetrics lends itself to multidisciplinary team training. It is a field in which nurses, midwives, obstetricians and paediatricians work together and where decisions must be made and actions must be carried out under extreme time pressure.</p> <p>It is attractive to belief that multidisciplinary team training will reduce the number of errors in obstetrics. The other side of the medal is that many hospitals are buying expensive patient simulators without proper evaluation of the training method. In the Netherlands many hospitals have 1,000 or less annual deliveries. In our small country it might therefore be more cost-effective to train obstetric teams in medical simulation centres with well trained personnel, high fidelity patient simulators, and well defined training programmes.</p> <p>Methods/design</p> <p>The aim of the present study is to evaluate the cost-effectiveness of multidisciplinary team training in a medical simulation centre in the Netherlands to reduce the number of medical errors in obstetric emergency situations. We plan a multicentre randomised study with the centre as unit of analysis. Obstetric departments will be randomly assigned to receive multidisciplinary team training in a medical simulation centre or to a control arm without any team training.</p> <p>The composite measure of poor perinatal and maternal outcome in the non training group was thought to be 15%, on the basis of data obtained from the National Dutch Perinatal Registry and the guidelines of the Dutch Society of Obstetrics and Gynaecology (NVOG). We anticipated that multidisciplinary team training would reduce this risk to 5%. A sample size of 24 centres with a cluster size of each at least 200 deliveries, each 12 centres per group, was needed for 80% power and a 5% type 1 error probability (two-sided). We assumed an Intraclass Correlation Coefficient (ICC) value of maximum 0.08.</p> <p>The analysis will be performed according to the intention-to-treat principle and stratified for teaching or non-teaching hospitals.</p> <p>Primary outcome is the number of obstetric complications throughout the first year period after the intervention. If multidisciplinary team training appears to be effective a cost-effective analysis will be performed.</p> <p>Discussion</p> <p>If multidisciplinary team training appears to be cost-effective, this training should be implemented in extra training for gynaecologists.</p> <p>Trial Registration</p> <p>The protocol is registered in the clinical trial register number NTR1859</p

Understanding organisational development, sustainability, and diffusion of innovations within hospitals participating in a multilevel quality collaborative

<p>Abstract</p> <p>Background</p> <p>Between 2004 and 2008, 24 Dutch hospitals participated in a two-year multilevel quality collaborative (MQC) comprised of (a) a leadership programme for hospital executives, (b) six quality-improvement collaboratives (QICs) for healthcare professionals and other staff, and (c) an internal programme organisation to help senior management monitor and coordinate team progress. The MQC aimed to stimulate the development of quality-management systems and the spread of methods to improve patient safety and logistics. The objective of this study is to describe how the first group of eight MQC hospitals sustained and disseminated improvements made and the quality methods used.</p> <p>Methods</p> <p>The approach followed by the hospitals was described using interview and questionnaire data gathered from eight programme coordinators.</p> <p>Results</p> <p>MQC hospitals followed a systematic strategy of diffusion and sustainability. Hospital quality-management systems are further developed according to a model linking plan-do-study-act cycles at the unit and hospital level. The model involves quality norms based on realised successes, performance agreements with unit heads, organisational support, monitoring, and quarterly accountability reports.</p> <p>Conclusions</p> <p>It is concluded from this study that the MQC contributed to organisational development and dissemination within participating hospitals. Organisational learning effects were demonstrated. System changes affect the context factors in the theory of organisational readiness: organisational culture, policies and procedures, past experience, organisational resources, and organisational structure. Programme coordinator responses indicate that these factors are utilised to manage spread and sustainability. Further research is needed to assess long-term effects.</p

Tomato Pathogenesis-related Protein Genes are Expressed in Response to Trialeurodes vaporariorum and Bemisia tabaci Biotype B Feeding

The temporal and spatial expression of tomato wound- and defense-response genes to Bemisia tabaci biotype B (the silverleaf whitefly) and Trialeurodes vaporariorum (the greenhouse whitefly) feeding were characterized. Both species of whiteflies evoked similar changes in tomato gene expression. The levels of RNAs for the methyl jasmonic acid (MeJA)- or ethylene-regulated genes that encode the basic β-1,3-glucanase (GluB), basic chitinase (Chi9), and Pathogenesis-related protein-1 (PR-1) were monitored. GluB and Chi9 RNAs were abundant in infested leaves from the time nymphs initiated feeding (day 5). In addition, GluB RNAs accumulated in apical non-infested leaves. PR-1 RNAs also accumulated after whitefly feeding. In contrast, the ethylene- and salicylic acid (SA)-regulated Chi3 and PR-4 genes had RNAs that accumulated at low levels and GluAC RNAs that were undetectable in whitefly-infested tomato leaves. The changes in Phenylalanine ammonia lyase5 (PAL5) were variable; in some, but not all infestations, PAL5 RNAs increased in response to whitefly feeding. PAL5 RNA levels increased in response to MeJA, ethylene, and abscisic acid, and declined in response to SA. Transcripts from the wound-response genes, leucine aminopeptidase (LapA1) and proteinase inhibitor 2 (pin2), were not detected following whitefly feeding. Furthermore, whitefly infestation of transgenic LapA1:GUS tomato plants showed that whitefly feeding did not activate the LapA1 promoter, although crushing of the leaf lamina increased GUS activity up to 40 fold. These studies indicate that tomato plants perceive B. tabaci and T. vaporariorum in a manner similar to baterical pathogens and distinct from tissue-damaging insects

Using and Reporting the Delphi Method for Selecting Healthcare Quality Indicators: A Systematic Review

OBJECTIVE: Delphi technique is a structured process commonly used to developed healthcare quality indicators, but there is a little recommendation for researchers who wish to use it. This study aimed 1) to describe reporting of the Delphi method to develop quality indicators, 2) to discuss specific methodological skills for quality indicators selection 3) to give guidance about this practice. METHODOLOGY AND MAIN FINDING: Three electronic data bases were searched over a 30 years period (1978-2009). All articles that used the Delphi method to select quality indicators were identified. A standardized data extraction form was developed. Four domains (questionnaire preparation, expert panel, progress of the survey and Delphi results) were assessed. Of 80 included studies, quality of reporting varied significantly between items (9% for year's number of experience of the experts to 98% for the type of Delphi used). Reporting of methodological aspects needed to evaluate the reliability of the survey was insufficient: only 39% (31/80) of studies reported response rates for all rounds, 60% (48/80) that feedback was given between rounds, 77% (62/80) the method used to achieve consensus and 57% (48/80) listed quality indicators selected at the end of the survey. A modified Delphi procedure was used in 49/78 (63%) with a physical meeting of the panel members, usually between Delphi rounds. Median number of panel members was 17(Q1:11; Q3:31). In 40/70 (57%) studies, the panel included multiple stakeholders, who were healthcare professionals in 95% (38/40) of cases. Among 75 studies describing criteria to select quality indicators, 28 (37%) used validity and 17(23%) feasibility. CONCLUSION: The use and reporting of the Delphi method for quality indicators selection need to be improved. We provide some guidance to the investigators to improve the using and reporting of the method in future surveys

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

Current and prospective pharmacological targets in relation to antimigraine action

Migraine is a recurrent incapacitating neurovascular disorder characterized by unilateral and throbbing headaches associated with photophobia, phonophobia, nausea, and vomiting. Current specific drugs used in the acute treatment of migraine interact with vascular receptors, a fact that has raised concerns about their cardiovascular safety. In the past, α-adrenoceptor agonists (ergotamine, dihydroergotamine, isometheptene) were used. The last two decades have witnessed the advent of 5-HT1B/1D receptor agonists (sumatriptan and second-generation triptans), which have a well-established efficacy in the acute treatment of migraine. Moreover, current prophylactic treatments of migraine include 5-HT2 receptor antagonists, Ca2+ channel blockers, and β-adrenoceptor antagonists. Despite the progress in migraine research and in view of its complex etiology, this disease still remains underdiagnosed, and available therapies are underused. In this review, we have discussed pharmacological targets in migraine, with special emphasis on compounds acting on 5-HT (5-HT1-7), adrenergic (α1, α2, and β), calcitonin gene-related peptide (CGRP 1 and CGRP2), adenosine (A1, A2, and A3), glutamate (NMDA, AMPA, kainate, and metabotropic), dopamine, endothelin, and female hormone (estrogen and progesterone) receptors. In addition, we have considered some other targets, including gamma-aminobutyric acid, angiotensin, bradykinin, histamine, and ionotropic receptors, in relation to antimigraine therapy. Finally, the cardiovascular safety of current and prospective antimigraine therapies is touched upon