The relationship between baseline Organizational Readiness to Change Assessment subscale scores and implementation of hepatitis prevention services in substance use disorders treatment clinics: a case study

<p>Abstract</p> <p>Background</p> <p>The Organizational Readiness to Change Assessment (ORCA) is a measure of organizational readiness for implementing practice change in healthcare settings that is organized based on the core elements and sub-elements of the Promoting Action on Research Implementation in Health Services (PARIHS) framework. General support for the reliability and factor structure of the ORCA has been reported. However, no published study has examined the utility of the ORCA in a clinical setting. The purpose of the current study was to examine the relationship between baseline ORCA scores and implementation of hepatitis prevention services in substance use disorders (SUD) clinics.</p> <p>Methods</p> <p>Nine clinic teams from Veterans Health Administration SUD clinics across the United States participated in a six-month training program to promote evidence-based practices for hepatitis prevention. A representative from each team completed the ORCA evidence and context subscales at baseline.</p> <p>Results</p> <p>Eight of nine clinics reported implementation of at least one new hepatitis prevention practice after completing the six-month training program. Clinic teams were categorized by level of implementation-high (n = 4) versus low (n = 5)-based on how many hepatitis prevention practices were integrated into their clinics after completing the training program. High implementation teams had significantly higher scores on the patient experience and leadership culture subscales of the ORCA compared to low implementation teams. While not reaching significance in this small sample, high implementation clinics also had higher scores on the research, clinical experience, staff culture, leadership behavior, and measurement subscales as compared to low implementation clinics.</p> <p>Conclusions</p> <p>The results of this study suggest that the ORCA was able to measure differences in organizational factors at baseline between clinics that reported high and low implementation of practice recommendations at follow-up. This supports the use of the ORCA to describe factors related to implementing practice recommendations in clinical settings. Future research utilizing larger sample sizes will be essential to support these preliminary findings.</p

Identification and Classification of Conserved RNA Secondary Structures in the Human Genome

The discoveries of microRNAs and riboswitches, among others, have shown functional RNAs to be biologically more important and genomically more prevalent than previously anticipated. We have developed a general comparative genomics method based on phylogenetic stochastic context-free grammars for identifying functional RNAs encoded in the human genome and used it to survey an eight-way genome-wide alignment of the human, chimpanzee, mouse, rat, dog, chicken, zebra-fish, and puffer-fish genomes for deeply conserved functional RNAs. At a loose threshold for acceptance, this search resulted in a set of 48,479 candidate RNA structures. This screen finds a large number of known functional RNAs, including 195 miRNAs, 62 histone 3′UTR stem loops, and various types of known genetic recoding elements. Among the highest-scoring new predictions are 169 new miRNA candidates, as well as new candidate selenocysteine insertion sites, RNA editing hairpins, RNAs involved in transcript auto regulation, and many folds that form singletons or small functional RNA families of completely unknown function. While the rate of false positives in the overall set is difficult to estimate and is likely to be substantial, the results nevertheless provide evidence for many new human functional RNAs and present specific predictions to facilitate their further characterization

Pharmacist-Driven Culture and Sexually Transmitted Infection Testing Follow-Up Program in the Emergency Department

Expanding pharmacist-driven antimicrobial stewardship efforts in the emergency department (ED) can improve antibiotic management for both admitted and discharged patients. We piloted a pharmacist-driven culture and rapid diagnostic technology (RDT) follow-up program in patients discharged from the ED. This was a single-center, pre- and post-implementation, cohort study examining the impact of a pharmacist-driven culture/RDT follow-up program in the ED. Adult patients discharged from the ED with subsequent positive cultures and/or RDT during the pre- (21 August 2018–18 November 2018) and post-implementation (19 November 2018–15 February 2019) periods were screened for inclusion. The primary endpoints were time from ED discharge to culture/RDT review and completion of follow-up. Secondary endpoints included antimicrobial agent prescribed during outpatient follow-up, repeat ED encounters within 30 days, and hospital admissions within 30 days. Baseline characteristics were analyzed using descriptive statistics. Time-to-event data were analyzed using the Wilcoxon signed-rank test. One-hundred-and-twenty-seven patients were included, 64 in the pre-implementation group and 63 in the post-implementation group. There was a 36.3% reduction in the meantime to culture/RDT data review in the post-implementation group (75.2 h vs. 47.9 h, p \u3c 0.001). There was a significant reduction in fluoroquinolone prescribing in the post-implementation group (18.1% vs. 5.4%, p = 0.036). The proportion of patients who had a repeat ED encounter or hospital admission within 30 days was not significantly different between the pre- and post-implementation groups (15.6 vs. 19.1%, p = 0.78 and 9.4% vs. 7.9%, p = 1.0, respectively). Introduction of a pharmacist culture and RDT follow-up program in the ED reduced time to data review, time to outpatient intervention and outpatient follow-up of fluoroquinolone prescribing

Primary spinal cord tumors of childhood: effects of clinical presentation, radiographic features, and pathology on survival

To determine the relationship between clinical presentation, radiographic features, pathology, and treatment on overall survival of newly diagnosed pediatric primary spinal cord tumors (PSCT). Retrospective analysis of all previously healthy children with newly diagnosed PSCT at a single institution from 1995 to present was performed. Twenty-five pediatric patients (15 boys, average 7.9 years) were diagnosed with PSCT. Presenting symptoms ranged from 0.25 to 60 months (average 7.8 months). Symptom duration was significantly shorter for high grade tumors (average 1.65 months) than low grade tumors (average 11.2 months) (P = 0.05). MRI revealed tumor (8 cervical, 17 thoracic, 7 lumbar, 7 sacral) volumes of 98–94,080 mm3 (average 19,474 mm3). Homogeneous gadolinium enhancement on MRI correlated with lower grade pathology (P = 0.003). There was no correlation between tumor grade and volume (P = 0.63) or edema (P = 0.36) by MRI analysis. Median survival was 53 months and was dependent on tumor grade (P = 0.05) and gross total resection (P = 0.01) but not on gender (P = 0.49), age of presentation (P = 0.82), duration of presenting symptoms (P = 0.33), or adjuvant therapies (P = 0.17). Stratified Kaplan–Meier analysis confirmed the association between degree of resection and survival after controlling for tumor grade (P = 0.01). MRI homogeneous gadolinium enhancement patterns may be helpful in distinguishing low grade from high grade spinal cord malignancies. While tumor grade and gross total resection rather than duration of symptoms correlated with survival in our series, greater than one-third of patients had reported symptoms greater than 6 months duration prior to diagnosis

Zebrafish Krüppel-Like Factor 4a Represses Intestinal Cell Proliferation and Promotes Differentiation of Intestinal Cell Lineages

BACKGROUND:Mouse krüppel-like factor 4 (Klf4) is a zinc finger-containing transcription factor required for terminal differentiation of goblet cells in the colon. However, studies using either Klf4(-/-) mice or mice with conditionally deleted Klf4 in their gastric epithelia showed different results in the role of Klf4 in epithelial cell proliferation. We used zebrafish as a model organism to gain further understanding of the role of Klf4 in the intestinal cell proliferation and differentiation. METHODOLOGY/PRINCIPAL FINDINGS:We characterized the function of klf4a, a mammalian klf4 homologue by antisense morpholino oligomer knockdown. Zebrafish Klf4a shared high amino acid similarities with human and mouse Klf4. Phylogenetic analysis grouped zebrafish Klf4a together with both human and mouse Klf4 in a branch with high bootstrap value. In zebrafish, we demonstrate that Klf4a represses intestinal cell proliferation based on results of BrdU incorporation, p-Histone 3 immunostaining, and transmission electron microscopy analyses. Decreased PepT1 expression was detected in intestinal bulbs of 80- and 102-hours post fertilization (hpf) klf4a morphants. Significant reduction of alcian blue-stained goblet cell number was identified in intestines of 102- and 120-hpf klf4a morphants. Embryos treated with γ-secretase inhibitor showed increased klf4a expression in the intestine, while decreased klf4a expression and reduction in goblet cell number were observed in embryos injected with Notch intracellular domain (NICD) mRNA. We were able to detect recovery of goblet cell number in 102-hpf embryos that had been co-injected with both klf4a and Notch 1a NICD mRNA. CONCLUSIONS/SIGNIFICANCE:This study provides in vivo evidence showing that zebrafih Klf4a is essential for the repression of intestinal cell proliferation. Zebrafish Klf4a is required for the differentiation of goblet cells and the terminal differentiation of enterocytes. Moreover, the regulation of differentiation of goblet cells in zebrafish intestine by Notch signaling at least partially mediated through Klf4a

A search using GEO600 for gravitational waves coincident with fast radio bursts from SGR 1935+2154

The magnetar SGR 1935+2154 is the only known Galactic source of fast radio bursts (FRBs). FRBs from SGR 1935+2154 were first detected by the Canadian Hydrogen Intensity Mapping Experiment (CHIME)/FRB and the Survey for Transient Astronomical Radio Emission 2 in 2020 April, after the conclusion of the LIGO, Virgo, and KAGRA Collaborations' O3 observing run. Here, we analyze four periods of gravitational wave (GW) data from the GEO600 detector coincident with four periods of FRB activity detected by CHIME/FRB, as well as X-ray glitches and X-ray bursts detected by NICER and NuSTAR close to the time of one of the FRBs. We do not detect any significant GW emission from any of the events. Instead, using a short-duration GW search (for bursts ≤1 s) we derive 50% (90%) upper limits of 1048 (1049) erg for GWs at 300 Hz and 1049 (1050) erg at 2 kHz, and constrain the GW-to-radio energy ratio to ≤1014−1016. We also derive upper limits from a long-duration search for bursts with durations between 1 and 10 s. These represent the strictest upper limits on concurrent GW emission from FRBs

Search for continuous gravitational waves from known pulsars in the first part of the fourth LIGO-Virgo-KAGRA observing run

Continuous gravitational waves (CWs) emission from neutron stars carries information about their internal structure and equation of state, and it can provide tests of general relativity. We present a search for CWs from a set of 45 known pulsars in the first part of the fourth LIGO–Virgo–KAGRA observing run, known as O4a. We conducted a targeted search for each pulsar using three independent analysis methods considering single-harmonic and dual-harmonic emission models. We find no evidence of a CW signal in O4a data for both models and set upper limits on the signal amplitude and on the ellipticity, which quantifies the asymmetry in the neutron star mass distribution. For the single-harmonic emission model, 29 targets have the upper limit on the amplitude below the theoretical spin-down limit. The lowest upper limit on the amplitude is 6.4 × 10−27 for the young energetic pulsar J0537−6910, while the lowest constraint on the ellipticity is 8.8 × 10−9 for the bright nearby millisecond pulsar J0437−4715. Additionally, for a subset of 16 targets, we performed a narrowband search that is more robust regarding the emission model, with no evidence of a signal. We also found no evidence of nonstandard polarizations as predicted by the Brans–Dicke theory

Dectin-1 Positive Dendritic Cells Expand after Infection with Leishmania major Parasites and Represent Promising Targets for Vaccine Development

Acknowledgments This work was supported by the Priority Program of the German Research Foundation (DFG) (RI 1849/2-1 and 4-1) and the Wellcome Trust (102705). We gratefully acknowledge our Ethiopian partners at the Armauer Hansen Research Institute, Addis Ababa. Rawleigh Howe for excellent supervision of flow cytometry analysis performed at the Armauer Hansen Research Institute and Selfu Girma, Birtukan Endale, Genet Amare and Hareg Yetesh for technical support during the field trips and laboratory work. Supplementary Material The Supplementary Material for this article can be found online at http://www.frontiersin.org/articles/10.3389/fimmu.2018.00263/full#supplementary-material.Peer reviewedPublisher PD