Novel patient-centered approach to facilitate same-day discharge in patients undergoing elective percutaneous coronary intervention

Background Same‐day discharge ( SDD ) after elective percutaneous coronary intervention is safe, less costly, and preferred by patients, but it is usually performed in low‐risk patients, if at all. To increase the appropriate use of SDD in more complex patients, we implemented a “patient‐centered” protocol based on risk of complications at Barnes‐Jewish Hospital. Methods and Results Our objectives were as follows: (1) to evaluate time trends in SDD ; (2) to compare (a) mortality, bleeding, and acute kidney injury, (b) patient satisfaction, and (c) hospital costs by SDD versus no SDD ( NSDD ); and (3) to compare SDD eligibility by our patient‐centered approach versus Society for Cardiovascular Angiography and Interventions guidelines. Our patient‐centered approach was based on prospectively identifying personalized bleeding, mortality, and acute kidney injury risks, with a personalized safe contrast limit and mitigating those risks. We analyzed Barnes‐Jewish Hospital's National Cardiovascular Data Registry Cath PCI Registry data from July 1, 2009 to September 30, 2015 (N=1752). SDD increased rapidly from 0% to 77% ( P &lt;0.001), independent of radial access. Although SDD patients were comparable to NSDD patients, SDD was not associated with adverse outcomes (0% mortality, 0% bleeds, and 0.4% acute kidney injury). Patient satisfaction was high with SDD . Propensity score–adjusted costs were 7331 lower/ SDD patient ( P <0.001), saving an estimated 1.8 million annually. Only 16 patients (6.95%) met the eligibility for SDD by Society for Cardiovascular Angiography and Interventions guidelines, implying our patient‐centered approach markedly increased SDD eligibility. Conclusions With a patient‐centered approach, SDD rapidly increased and was safe in 75% of patients undergoing elective percutaneous coronary intervention, despite patient complexity. Patient satisfaction was high, and hospital costs were lower. Patient‐centered decision making to facilitate SDD is an important opportunity to improve the value of percutaneous coronary intervention. </jats:sec

Traffic Forecasting for Pavement Design

The need for improved traffic estimation procedures has been emphasized by several studies that demonstrated that previously available data were not adequate. Some data were not considered representative of actual traffic conditions because of overloaded trucks avoiding weighing scales and insufficient traffic sampling programs. In addition, previous forecasting procedures did not reflect the increases in legal load limits, the significant increase in the number of heavy trucks, or the shift toward larger vehicle types that has occurred in recent years. Improved estimates of current traffic loadings based on larger samples of much higher quality data would allow development of procedures for making improved estimates of historical traffic loadings and better forecasts of traffic loadings during the design period. The emergence of automatic vehicle classification equipment, permanent and portable weigh-in-motion (WIM) systems, and the application of microprocessors and microcomputers to these data acquisition functions now offer tools that may be used effectively in meeting these needs. Representatives from four States (Florida, Kentucky, Oregon, and Washington) met on several occasions to discuss the subject of traffic forecasting for pavement design. Information was compiled on all aspects of the traffic forecasting process, options were presented for each step of the process, and recommendations were developed to assist highway agencies in improving current practices and procedures

A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP

The innate immune system responds to unique molecular signatures that are widely conserved among microbes but that are not normally present in host cells. Compounds that stimulate innate immune pathways may be valuable in the design of novel adjuvants, vaccines, and other immunotherapeutics. The cyclic dinucleotide cyclic-di–guanosine monophosphate (c-di-GMP) is a recently appreciated second messenger that plays critical regulatory roles in many species of bacteria but is not produced by eukaryotic cells. In vivo and in vitro studies have previously suggested that c-di-GMP is a potent immunostimulatory compound recognized by mouse and human cells. We provide evidence that c-di-GMP is sensed in the cytosol of mammalian cells via a novel immunosurveillance pathway. The potency of cytosolic signaling induced by c-di-GMP is comparable to that induced by cytosolic delivery of DNA, and both nucleic acids induce a similar transcriptional profile, including triggering of type I interferons and coregulated genes via induction of TBK1, IRF3, nuclear factor κB, and MAP kinases. However, the cytosolic pathway that senses c-di-GMP appears to be distinct from all known nucleic acid–sensing pathways. Our results suggest a novel mechanism by which host cells can induce an inflammatory response to a widely produced bacterial ligand

Identification of Host Cytosolic Sensors and Bacterial Factors Regulating the Type I Interferon Response to Legionella pneumophila

Legionella pneumophila is a gram-negative bacterial pathogen that replicates in host macrophages and causes a severe pneumonia called Legionnaires' Disease. The innate immune response to L. pneumophila remains poorly understood. Here we focused on identifying host and bacterial factors involved in the production of type I interferons (IFN) in response to L. pneumophila. It was previously suggested that the delivery of L. pneumophila DNA to the host cell cytosol is the primary signal that induces the type I IFN response. However, our data are not easily reconciled with this model. We provide genetic evidence that two RNA-sensing proteins, RIG-I and MDA5, participate in the IFN response to L. pneumophila. Importantly, these sensors do not seem to be required for the IFN response to L. pneumophila DNA, whereas we found that RIG-I was required for the response to L. pneumophila RNA. Thus, we hypothesize that bacterial RNA, or perhaps an induced host RNA, is the primary stimulus inducing the IFN response to L. pneumophila. Our study also identified a secreted effector protein, SdhA, as a key suppressor of the IFN response to L. pneumophila. Although viral suppressors of cytosolic RNA-sensing pathways have been previously identified, analogous bacterial factors have not been described. Thus, our results provide new insights into the molecular mechanisms by which an intracellular bacterial pathogen activates and also represses innate immune responses

Recent visible light and metal free strategies in [2+2] and [4+2] photocycloadditions

When aiming to synthesize molecules with elevated molecular complexity starting from relatively simple starting materials, photochemical transformations represent an open avenue to circumvent analogous multistep procedures. Specifically, light-mediated cycloadditions remain as powerful tools to generate new bonds begotten from non-very intuitive disconnections, that alternative thermal protocols would not offer. In response to the current trend in both industrial and academic research pointing towards green and sustainable processes, several strategies that meet these requirements are currently available in the literature. This Minireview summarizes [2+2] and [4+2] photocycloadditions that do not require the use of metal photocatalysts by means of alternative strategies. It is segmented according to the cycloaddition type in order to give the reader a friendly approach and we primarily focus on the most recent developments in the field carried out using visible light, a general overview of the mechanism in each case is offered as wellFinancial support was provided by the European Research Council (ERC-CoG, Contract Number: 647550), the Spanish Government (RTI2018-095038-B-I00), the ‘Comunidad de Madrid’ and European Structural Funds (S2018/NMT-4367). R. I. R thanks Fundación Carolina for a graduate fellowshi

Phenotypic insights into ADCY5-associated disease

Background Adenylyl cyclase 5 (ADCY5) mutations is associated with heterogenous syndromes: familial dyskinesia and facial myokymia; paroxysmal chorea and dystonia; autosomal‐dominant chorea and dystonia; and benign hereditary chorea. We provide detailed clinical data on 7 patients from six new kindreds with mutations in the ADCY5 gene, in order to expand and define the phenotypic spectrum of ADCY5 mutations. Methods In 5 of the 7 patients, followed over a period of 9 to 32 years, ADCY5 was sequenced by Sanger sequencing. The other 2 unrelated patients participated in studies for undiagnosed pediatric hyperkinetic movement disorders and underwent whole‐exome sequencing. Results Five patients had the previously reported p.R418W ADCY5 mutation; we also identified two novel mutations at p.R418G and p.R418Q. All patients presented with motor milestone delay, infantile‐onset action‐induced generalized choreoathetosis, dystonia, or myoclonus, with episodic exacerbations during drowsiness being a characteristic feature. Axial hypotonia, impaired upward saccades, and intellectual disability were variable features. The p.R418G and p.R418Q mutation patients had a milder phenotype. Six of seven patients had mild functional gain with clonazepam or clobazam. One patient had bilateral globus pallidal DBS at the age of 33 with marked reduction in dyskinesia, which resulted in mild functional improvement. Conclusion We further delineate the clinical features of ADCY5 gene mutations and illustrate its wide phenotypic expression. We describe mild improvement after treatment with clonazepam, clobazam, and bilateral pallidal DBS. ADCY5‐associated dyskinesia may be under‐recognized, and its diagnosis has important prognostic, genetic, and therapeutic implications

Measuring floral resource availability for insect pollinators in temperate grasslands – a review

Abstract. 1. The relationship between pollinators and flowering plants plays a crucial role in the function of terrestrial ecosystems. Although pollinators use floral nectar and pollen as food resources, no general methodology for floral resource availability estimates exists. 2. A brief review is provided on floral resource sampling methods frequently used in pollination studies. The focus is on how representative vegetation samples are both spatially and temporally, and how these are constrained by sampling effort. 3. Field studies investigating flowering plant abundance for insect pollinators in temperate grasslands were selected. We categorised the reviewed studies according to aims, sampling units, and count variables used and provide a descriptive summary on methodology. We also searched for trade-offs between different aspects of sampling investment. 4. One hundred and fifty-eight pollination studies were reviewed. Large methodolog- ical differences were found, and vegetation sampling was presented in many studies insufficiently. Sampling covered a small proportion (median: 0.69%) of the study sites, with long intervals (median: 30 days), and most studies lasted only a few years. The most often used count variables were indirect proxies of floral resources. Negative relation- ships were found in some of the different aspects of sampling, e.g. the proportion of site covered with sampling decreased with increasing site area. 5. By tailoring sampling methods to specific research questions, research effort should be optimally allocated to obtain proper spatio-temporal resolution and data coverage. Guidelines were suggested to design sampling, e.g. to increase coverage and frequency. Further field work on optimising sampling techniques is mandatory

Vulnerability of Pollination Ecosystem Services

Humans are dependent on pollinators for food security and for a vast number of services mediated by wild and cultivated plants, yet we know little about how pollination services could be affected by changes in local and regional climate. In this chapter, we review the current literature on pollination services and environmental change and provide ecologically informed suggestions for managing pollination services, focusing on native pollinators. Our management suggestions are intended to be generalizable for scientists and policy makers across communities and ecoregions. © 2013 Elsevier Inc. All rights reserved

A rhetoric of digression, the discursive critique of ratiocentrism in the major novels of middle Bellow, 1953-1975

grantor: University of TorontoOne of the most striking formal attributes of Saul Bellow's fiction is its digressivity, and the tendency of Bellovian narrative to wander and return is particularly pronounced in the long fiction of the author's middle period (1953-1975). From 'The Adventures of Augie March' (1953) to 'Humboldt's Gift' (1975), by way of 'Henderson the Rain King' (1959), 'Herzog' (1964), and 'Mr. Sammler's Planet' (1970), Bellow's novelistic fiction manifests an incremental shift of emphasis from plot to theme and from action to reflection. Both the articulation of theme and the representation of reflection--increasingly the former by means of the latter--are accommodated by the creative variety of digressive means Bellow employs to effect suspensions of the narrative of event. At least four major patterns of digression can be discerned in middle Bellow: dialogic, narratorial, epistolary, and meditative. By means of dialogues that are monologic in 'Augie' and univocal in 'Sammler ', narration that is eccentric and discursive in 'Henderson ', epistolary techniques that are peculiar to 'Herzog', and detailed representations of meditative withdrawals that are unique to ' Humboldt', Bellow voices his fundamental protest against the modern world: secularism and science, by subordinating other human faculties to reason, have given humankind an impoverished conception of itself and its abilities. Refusing to be bound by secular dogmas or the scientific world view, Bellow employs a rhetoric of digression to provide a space within his fiction where his counterposition emerges in a counternarrative of affirmation, the principal tenets of which are the existence of the soul, the primacy of the imagination, and the necessity of suprarational epistemology.Ph.D