Coalition theories: empirical evidence for dutch municipalities

The paper analyzes coalition formation in Dutch municipalities. After discussing the main features of the institutional setting, several theories are discussed, which are classified as size oriented, policy oriented and actor oriented models. A test statistic is proposed to determine the predictive power of these models. The empirical analysis shows that strategic positions as well as some of the distinguished preferences are important in the setting of Dutch municipalities. Especially, the dominant minimum number principle yields highly significant results for coalition formations in the period 1978–1986

Am empirical comparison of the performance of classical power indices

Power indices are general measures of the relative voting power of individual members of a voting body. They are useful in helping understand and design voting bodies particularly those which employ weighted voting, in which different members having different numbers of votes. It is well known that in such bodies a member's voting power, in the sense of their capacity to affect the outcomes of votes called, rarely corresponds to the actual number of votes allocated to him. Many voting bodies for which this is an important consideration exist: examples include international organisations (notably the World Bank, the IMF, the European Union), the US presidential Electoral College and corporations in which votes are proportionate to stockholdings. Two classical power indices dominate the literature: the Shapley-Shubik index and the Banzhaf index (also known by other names). Both are based on the idea that a member's power depends on the relative number of times they can change a coalition from losing to winning by joining it and adding their vote. They may be defined in probabilistic terms as the probability of being able to swing the result of a vote, where all possible outcomes are taken as equiprobable. The indices differ however in the way they count voting coalitions. In probabilistic terms they use different coalition models and therefore differ in precisely what is meant by equiprobable outcomes. The indices have been used in a number of empirical applications but their relative performance has remained an open question for many years, a factor, which has hindered the wider acceptance of the approach. Where both the indices have been used for the same case, they have often given different results, sometimes substantially so, and theoretical studies of their properties have not been conclusive. There is therefore a need for comparative testing of their relative performance in practical contexts. Very little work of this type has been done however for a number of reasons: lack of independent indicators of power in actual voting bodies with which to compare them, difficulties in obtaining consistent data on a voting body over time with sufficient variation in the disposition of votes among members of actual legislatures and the lack of independent criteria against which the results of the indices may be judged. It has also been hampered to some extent by lack of easily available algorithms for computing the indices in large games. This paper assesses the indices against a set of reasonable criteria in terms of shareholder voting power and the control of the corporation in a large cross section of British companies. Each company is a separate voting body and there is much variation in the distribution of voting shares among them. Moreover reasonable criteria exist against which to judge the indices. New algorithms for the Shapley-Shubik and Banzhaf indices are applied to detailed data on beneficial ownership of 444 large UK companies without majority control. Because some of the data is missing, both finite and oceanic games of shareholder voting are studied to overcome this problem. The results, judged against these criteria, are unfavorable to the Shapley-Shubik index and suggest that the Banzhaf index much better reflects the variations in the power of shareholders between companies as the weights of shareholder blocks vary

A functional riboSNitch in the 3' untranslated region of FKBP5 alters MicroRNA-320a binding efficiency and mediates vulnerability to chronic post-traumatic pain

Previous studies have shown that common variants of the gene coding for FK506-binding protein 51 (FKBP5), a critical regulator of glucocorticoid sensitivity, affect vulnerability to stress-related disorders. In a previous report, FKBP5 rs1360780 was identified as a functional variant because of its effect on gene methylation. Here we report evidence for a novel functional FKBP5 allele, rs3800373. This study assessed the association between rs3800373 and post-traumatic chronic pain in 1607 women and men from two ethnically diverse human cohorts. The molecular mechanism through which rs3800373 affects adverse outcomes was established via in silico, in vivo, and in vitro analyses. The rs3800373 minor allele predicted worse adverse outcomes after trauma exposure, such that individuals with the minor (risk) allele developed more severe post-traumatic chronic musculoskeletal pain. Among these individuals, peritraumatic circulating FKBP5 expression levels increased as cortisol and glucocorticoid receptor (NR3C1) mRNA levels increased, consistent with increased glucocorticoid resistance. Bioinformatic, in vitro, and mutational analyses indicate that the rs3800373 minor allele reduces the binding of a stress-and pain-associated microRNA, miR-320a, to FKBP5 via altering the FKBP5 mRNA 3'UTR secondary structure (i.e., is a riboSNitch). This results in relatively greater FKBP5 translation, unchecked by miR-320a. Overall, these results identify an important gene–miRNA interaction influencing chronic pain risk in vulnerable individuals and suggest that exogenous methods to achieve targeted reduction in poststress FKBP5 mRNA expression may constitute useful therapeutic strategies

The Magdalena Ridge Observatory Interferometer: 2014 status update

The Magdalena Ridge Observatory Interferometer has been designed to be a 10 × 1.4 m aperture long-baseline optical/near-infrared interferometer in an equilateral "Y" configuration, and is being deployed west of Socorro, NM on the Magdalena Ridge. Unfortunately, first light for the facility has been delayed due to the current difficult funding regime, but during the past two years we have made substantial progress on many of the key subsystems for the array. The design of all these subsystems is largely complete, and laboratory assembly and testing, and the installation and site acceptance testing of key components on the Ridge are now underway. This paper serves as an overview and update on the facility's present status and changes since 2012, and the plans for future activities and eventual operations of the facilities. © (2014) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.The Magdalena Ridge Observatory Interferometer is funded by the U.S. Department of Transportation, the State of New Mexico, and New Mexico Tech with previous funding from the Navy Research Laboratory (NRL, agreement no. N00173-01-2-C902).This is the final published version of the article, also available from SPIE at http://proceedings.spiedigitallibrary.org/proceeding.aspx?articleid=1891908. Copyright 2014 Society of Photo Optical Instrumentation Engineers. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited. http://dx.doi.org/10.1117/12.205733

Peptide Ligands for Pro-survival Protein Bfl-1 from Computationally Guided Library Screening

Pro-survival members of the Bcl-2 protein family inhibit cell death by binding short helical BH3 motifs in pro-apoptotic proteins. Mammalian pro-survival proteins Bcl-x[subscript L], Bcl-2, Bcl-w, Mcl-1, and Bfl-1 bind with varying affinities and specificities to native BH3 motifs, engineered peptides, and small molecules. Biophysical studies have determined interaction patterns for these proteins, particularly for the most-studied family members Bcl-x[subscript L] and Mcl-1. Bfl-1 is a pro-survival protein implicated in preventing apoptosis in leukemia, lymphoma, and melanoma. Although Bfl-1 is a promising therapeutic target, relatively little is known about its binding preferences. We explored the binding of Bfl-1 to BH3-like peptides by screening a peptide library that was designed to sample a high degree of relevant sequence diversity. Screening using yeast-surface display led to several novel high-affinity Bfl-1 binders and to thousands of putative binders identified through deep sequencing. Further screening for specificity led to identification of a peptide that bound to Bfl-1 with K[subscript d] < 1 nM and very slow dissociation from Bfl-1 compared to other pro-survival Bcl-2 family members. A point mutation in this sequence gave a peptide with ~50 nM affinity for Bfl-1 that was selective for Bfl-1 in equilibrium binding assays. Analysis of engineered Bfl-1 binders deepens our understanding of how the binding profiles of pro-survival proteins differ and may guide the development of targeted Bfl-1 inhibitors.National Institute of General Medical Sciences (U.S.) (Award GM084181)National Institute of General Medical Sciences (U.S.) (Award P50-GM68762

Design of Clinical Trials Evaluating Sedation in Critically Ill Adults Undergoing Mechanical Ventilation

Objectives: Clinical trials evaluating the safety and effectiveness of sedative medication use in critically ill adults undergoing mechanical ventilation differ considerably in their methodological approach. This heterogeneity impedes the ability to compare results across studies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations convened a meeting of multidisciplinary experts to develop recommendations for key methodologic elements of sedation trials in the ICU to help guide academic and industry clinical investigators. Design: A 2-day in-person meeting was held in Washington, DC, on March 28–29, 2019, followed by a three-round, online modified Delphi consensus process. Participants: Thirty-six participants from academia, industry, and the Food and Drug Administration with expertise in relevant content areas, including two former ICU patients attended the in-person meeting, and the majority completed an online follow-up survey and participated in the modified Delphi process. Measurements and Main Results: The final recommendations were iteratively refined based on the survey results, participants’ reactions to those results, summaries written by panel moderators, and a review of the meeting transcripts made from audio recordings. Fifteen recommendations were developed for study design and conduct, subject enrollment, outcomes, and measurement instruments. Consensus recommendations included obtaining input from ICU survivors and/or their families, ensuring adequate training for personnel using validated instruments for assessments of sedation, pain, and delirium in the ICU environment, and the need for methodological standardization. Conclusions: These recommendations are intended to assist researchers in the design, conduct, selection of endpoints, and reporting of clinical trials involving sedative medications and/or sedation protocols for adult ICU patients who require mechanical ventilation. These recommendations should be viewed as a starting point to improve clinical trials and help reduce methodological heterogeneity in future clinical trials

Wean Earlier and Automatically with New technology (the WEAN study): a protocol of a multicentre, pilot randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Weaning is the process during which mechanical ventilation is withdrawn and the work of breathing is transferred from the ventilator back to the patient. Prolonged weaning is associated with development of ventilator-related complications and longer stays in the Intensive Care Unit (ICU). Computerized or Automated Weaning is a novel weaning strategy that continuously measures and adapts ventilator support (by frequently measuring and averaging three breathing parameters) and automatically conducts Spontaneous Breathing Trials to ascertain whether patients can resume autonomous breathing. Automated Weaning holds promise as a strategy to reduce the time spent on the ventilator, decrease ICU length of stay, and improve clinically important outcomes.</p> <p>Methods/Design</p> <p>A pilot weaning randomized controlled trial (RCT) is underway in the ICUs of 8 Canadian hospitals. We will randomize 90 critically ill adults requiring invasive ventilation for at least 24 hours and identified at an early stage of the weaning process to either Automated Weaning (SmartCare™) or Protocolized Weaning. The results of a National Weaning Survey informed the design of the Protocolized Weaning arm. Both weaning protocols are operationalized in Pressure Support mode, include opportunities for Spontaneous Breathing Trials, and share a common sedation protocol, oxygen titration parameters, and extubation and reintubation criteria. The primary outcome of the WEAN study is to evaluate compliance with the proposed weaning and sedation protocols. A key secondary outcome of the pilot RCT is to evaluate clinician acceptance of the weaning and sedation protocols. Prior to initiating the WEAN Study, we conducted a run-in phase, involving two patients per centre (randomizing the first participant to either weaning strategy and assigning the second patient to the alternate strategy) to ensure that participating centres could implement the weaning and sedation protocols and complete the detailed case report forms.</p> <p>Discussion</p> <p>Mechanical ventilation studies are difficult to implement; requiring protocols to be operationalized continuously and entailing detailed daily data collection. As the first multicentre weaning RCT in Canada, the WEAN Study seeks to determine the feasibility of conducting a large scale future weaning trial and to establish a collaborative network of ICU clinicians dedicated to advancing the science of weaning.</p> <p>Trial Registration Number</p> <p>ISRCTN43760151</p