Individual Nurse Productivity in Preparing Patients for Discharge Is Associated with Patient Likelihood of 30-Day Return to Hospital

Objective: Applied to value-based health care, the economic term “individual productivity” refers to the quality of an outcome attributable through a care process to an individual clinician. This study aimed to (1) estimate and describe the discharge preparation productivities of individual acute care nurses and (2) examine the association between the discharge preparation productivity of the discharging nurse and the patient’s likelihood of a 30-day return to hospital [readmission and emergency department (ED) visits]. Research Design: Secondary analysis of patient-nurse data from a cluster-randomized multisite study of patient discharge readiness and readmission. Patients reported discharge readiness scores; postdischarge outcomes and other variables were extracted from electronic health records. Using the structure-process-outcomes model, we viewed patient readiness for hospital discharge as a proximal outcome of the discharge preparation process and used it to measure nurse productivity in discharge preparation. We viewed hospital return as a distal outcome sensitive to discharge preparation care. Multilevel regression analyses used a split-sample approach and adjusted for patient characteristics. Subjects: A total 522 nurses and 29,986 adult (18+ y) patients discharged to home from 31 geographically diverse medical-surgical units between June 15, 2015 and November 30, 2016. Measures: Patient discharge readiness was measured using the 8-item short form of Readiness for Hospital Discharge Scale (RHDS). A 30-day hospital return was a categorical variable for an inpatient readmission or an ED visit, versus no hospital return. Results: Variability in individual nurse productivity explained 9.07% of variance in patient discharge readiness scores. Nurse productivity was negatively associated with the likelihood of a readmission (−0.48 absolute percentage points, P\u3c0.001) and an ED visit (−0.29 absolute percentage points, P=0.042). Conclusions: Variability in individual clinician productivity can have implications for acute care quality patient outcomes

The Infrared Imaging Spectrograph (IRIS) for TMT: Data Reduction System

IRIS (InfraRed Imaging Spectrograph) is the diffraction-limited first light instrument for the Thirty Meter Telescope (TMT) that consists of a near-infrared (0.84 to 2.4 $\mu$m) imager and integral field spectrograph (IFS). The IFS makes use of a lenslet array and slicer for spatial sampling, which will be able to operate in 100's of different modes, including a combination of four plate scales from 4 milliarcseconds (mas) to 50 mas with a large range of filters and gratings. The imager will have a field of view of 34$\times$34 arcsec$^{2}$ with a plate scale of 4 mas with many selectable filters. We present the preliminary design of the data reduction system (DRS) for IRIS that need to address all of these observing modes. Reduction of IRIS data will have unique challenges since it will provide real-time reduction and analysis of the imaging and spectroscopic data during observational sequences, as well as advanced post-processing algorithms. The DRS will support three basic modes of operation of IRIS; reducing data from the imager, the lenslet IFS, and slicer IFS. The DRS will be written in Python, making use of open-source astronomical packages available. In addition to real-time data reduction, the DRS will utilize real-time visualization tools, providing astronomers with up-to-date evaluation of the target acquisition and data quality. The quicklook suite will include visualization tools for 1D, 2D, and 3D raw and reduced images. We discuss the overall requirements of the DRS and visualization tools, as well as necessary calibration data to achieve optimal data quality in order to exploit science cases across all cosmic distance scales.Comment: 13 pages, 2 figures, 6 tables, Proceeding 9913-165 of the SPIE Astronomical Telescopes + Instrumentation 201

Effects of increasing the affinity of CarD for RNA polymerase on Mycobacterium tuberculosis growth, rRNA transcription, and virulence

CarD is an essential RNA polymerase (RNAP) interacting protein in Mycobacterium tuberculosis that stimulates formation of RNAP-promoter open complexes. CarD plays a complex role in M. tuberculosis growth and virulence that is not fully understood. Therefore, to gain further insight into the role of CarD in M. tuberculosis growth and virulence, we determined the effect of increasing the affinity of CarD for RNAP. Using site-directed mutagenesis guided by crystal structures of CarD bound to RNAP, we identified amino acid substitutions that increase the affinity of CarD for RNAP. Using these substitutions, we show that increasing the affinity of CarD for RNAP increases the stability of the CarD protein in M. tuberculosis. In addition, we show that increasing the affinity of CarD for RNAP increases the growth rate in M. tuberculosis without affecting 16S rRNA levels. We further show that increasing the affinity of CarD for RNAP reduces M. tuberculosis virulence in a mouse model of infection despite the improved growth rate in vitro. Our findings suggest that the CarD-RNAP interaction protects CarD from proteolytic degradation in M. tuberculosis, establish that growth rate and rRNA levels can be uncoupled in M. tuberculosis and demonstrate that the strength of the CarD-RNAP interaction has been finely tuned to optimize virulence. IMPORTANCE Mycobacterium tuberculosis, the causative agent of tuberculosis, remains a major global health problem. In order to develop new strategies to battle this pathogen, we must gain a better understanding of the molecular processes involved in its survival and pathogenesis. We have previously identified CarD as an essential transcriptional regulator in mycobacteria. In this study, we detail the effects of increasing the affinity of CarD for RNAP on transcriptional regulation, CarD protein stability, and virulence. These studies expand our understanding of the global transcription regulator CarD, provide insight into how CarD activity is regulated, and broaden our understanding of prokaryotic transcription

Gene expression in Leishmania is regulated predominantly by gene dosage

ABSTRACT Leishmania tropica, a unicellular eukaryotic parasite present in North and East Africa, the Middle East, and the Indian subcontinent, has been linked to large outbreaks of cutaneous leishmaniasis in displaced populations in Iraq, Jordan, and Syria. Here, we report the genome sequence of this pathogen and 7,863 identified protein-coding genes, and we show that the majority of clinical isolates possess high levels of allelic diversity, genetic admixture, heterozygosity, and extensive aneuploidy. By utilizing paired genome-wide high-throughput DNA sequencing (DNA-seq) with RNA-seq, we found that gene dosage, at the level of individual genes or chromosomal “somy” (a general term covering disomy, trisomy, tetrasomy, etc.), accounted for greater than 85% of total gene expression variation in genes with a 2-fold or greater change in expression. High gene copy number variation (CNV) among membrane-bound transporters, a class of proteins previously implicated in drug resistance, was found for the most highly differentially expressed genes. Our results suggest that gene dosage is an adaptive trait that confers phenotypic plasticity among natural Leishmania populations by rapid down- or upregulation of transporter proteins to limit the effects of environmental stresses, such as drug selection. IMPORTANCE Leishmania is a genus of unicellular eukaryotic parasites that is responsible for a spectrum of human diseases that range from cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL) to life-threatening visceral leishmaniasis (VL). Developmental and strain-specific gene expression is largely thought to be due to mRNA message stability or posttranscriptional regulatory networks for this species, whose genome is organized into polycistronic gene clusters in the absence of promoter-mediated regulation of transcription initiation of nuclear genes. Genetic hybridization has been demonstrated to yield dramatic structural genomic variation, but whether such changes in gene dosage impact gene expression has not been formally investigated. Here we show that the predominant mechanism determining transcript abundance differences (>85%) in Leishmania tropica is that of gene dosage at the level of individual genes or chromosomal somy

A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis.

BACKGROUND: Platelet glycoprotein IIb/IIIa is a membrane receptor for fibrinogen and von Willebrand factor, and it has an important role in platelet aggregation. It is known to be involved in the pathogenesis of acute coronary syndromes. Previously, we found a high frequency of a particular polymorphism, PlA2, of the gene encoding glycoprotein IIIa in kindreds with a high prevalence of premature myocardial infarction. METHODS: To investigate the relation between the PlA2 polymorphism and acute coronary syndromes, we conducted a case-control study of 71 case patients with myocardial infarction or unstable angina and 68 inpatient controls without known heart disease. The groups were matched for age, race, and sex. We used two methods to determine the PlA genotype: reverse dot blot hybridization and allele-specific restriction digestion. RESULTS: The prevalence of PlA2 was 2.1 times higher among the case patients than among the controls (39.4 percent vs. 19.1 percent, P=0.01). In a subgroup of patients whose disease began before the age of 60 years, the prevalence of PlA2 was 50 percent, a value that was 3.6 times that among control subjects under 60 years of age (13.9 percent, P=0.002). Among subjects with the PlA2 polymorphism, the odds ratio for having a coronary event was 2.8 (95 percent confidence interval, 1.2 to 6.4). In the patients less than 60 years of age at the onset of disease, the odds ratio was 6.2 (95 percent confidence interval, 1.8 to 22.4). CONCLUSIONS: We observed a strong association between the PlA2 polymorphism of the glycoprotein IIIa gene and acute coronary thrombosis, and this association was strongest in patients who had had coronary events before the age of 60 years

Refining the Pediatric Multiple Organ Dysfunction Syndrome

Since its introduction into the medical literature in the 1970s, the term multiple organ dysfunction syndrome (or some variant) has been applied broadly to any patient with >1 concurrent organ dysfunction. However, the epidemiology, mechanisms, time course, and outcomes among children with multiple organ dysfunction vary substantially. We posit that the term pediatric multiple organ dysfunction syndrome (or MODS) should be reserved for patients with a systemic pathologic state resulting from a common mechanism (or mechanisms) that affects numerous organ systems simultaneously. In contrast, children in whom organ injuries are attributable to distinct mechanisms should be considered to have additive organ system dysfunctions but not the syndrome of MODS. Although such differentiation may not always be possible with current scientific knowledge, we make the case for how attempts to differentiate multiple organ dysfunction from other states of additive organ dysfunctions can help to evolve clinical and research priorities in diagnosis, monitoring, and therapy from largely organ-specific to more holistic strategies