Assessment of Customer Perceptions of the Hazardous Materials Pharmacy

The Air Force began operations of a Hazardous Material Pharmacy (HMP) in the late 80s. This thesis identifies causes of positive and negative perceptions of the HMP among its customers. Focus groups were used to determine customer perceptions. Several Total Quality Management (TQM) tools were used in this analysis. Brainstorming was used to generate customer perceptions. Affinity diagrams were used to group data into meaningful categories. Interrelationship digraphs were used to determine influence among causes of perception and to rank the causes of perception. This study showed that lack of clear policy and support of the HMP were the leading causes of negative perception of the HMP. No category of positive perception was determined to be most significant. Additionally, the areas of information flow, training, continuity, support, and personnel issues within the HMP represent possible areas for improvement

A Composite Metric for Benchmarking Site Performance in TAVR: Results from the STS/ACC TVT Registry

Background: Transcatheter aortic valve replacement (TAVR) is a transformative therapy for aortic stenosis. Despite rapid improvements in technology and techniques, serious complications remain relatively common and are not well described by single outcome measures. The purpose of this study was to determine if there is site-level variation in TAVR outcomes in the United States using a novel 30-day composite measure. Methods: We performed a retrospective cohort study using data from the STS/ACC TVT Registry to develop a novel ranked composite performance measure that incorporates mortality and serious complications. The selection and rank order of the complications for the composite was determined by their adjusted association with 1-year outcomes. Sites whose risk-adjusted outcomes were significantly more or less frequent than the national average based on a 95% probability interval were classified as performing worse or better than expected. Results: The development cohort consisted of 52,561 patients who underwent TAVR between January 1, 2015 and December 31, 2017. Based on the associations with 1-year risk-adjusted mortality and health status, we identified four periprocedural complications to include in the composite risk model in addition to mortality. Ranked empirically according to severity, these included stroke, major, life-threatening or disabling bleeding, stage III acute kidney injury, and moderate or severe peri-valvular regurgitation. Based on these ranked outcomes, we found that there was significant site-level variation in quality of care in TAVR in the United States. Overall, better than expected site performance was observed in 25/301 (8%) of sites; performance as expected was observed in 242/301 sites (80%); and worse than expected performance was observed in 34/301 (11%) of sites. Thirty-day mortality, stroke, major, life-threatening or disabling bleeding, and moderate or severe peri-valvular leak were each substantially more common in sites with worse than expected performance as compared with other sites. There was good aggregate reliability of the model. Conclusions: There are substantial variations in the quality of TAVR care received in the United States, and 11% of sites were identified as providing care below the average level of performance. Further study is necessary to determine structural, process-related, and technical factors associated with high- and low-performing sites

Robust Inference of Monocot Deep Phylogeny Using an Expanded Multigene Plastid Data Set

We use multiple photosynthetic, chlororespiratory, and plastid translation apparatus loci and their associated noncoding regions (ca. 16 kb per taxon, prior to alignment) to make strongly supported inferences of the deep internal branches of monocot phylogeny. Most monocot relationships are robust (an average of ca. 91 % bootstrap support per branch examined), including those poorly supported or unresolved in other studies. Our data strongly support a sister-group relationship between Asparagales and the commelinid monocots, the inclusion of the orchids in Asparagales, and the status of Petrosaviaceae as the sister group of all monocots except Acorus and Alismatales. The latter finding supports recognition of the order Petrosaviales. Also strongly supported is a placement of Petermannia disjunct from Colchicaceae (Liliales) and a sister-group relationship between Commelinales and Zingiberales. We highlight the remaining weak areas of monocot phylogeny, including the positions of Dioscoreales, Liliales, and Pandanales. Despite substantial variation in the overall rate of molecular evolution among lineages, inferred amounts of change among codon-position data partitions are correlated with each other across the monocot tree, consistent with low incongruence between these partitions. Ceratophyllum and Chloranthaceae appear to have a destabilizing effect on the position of the monocots among other angiosperms; the issue of monocot placement in broader angiosperm phylogeny remains problematic

Transcriptional regulatory control of mammalian nephron progenitors revealed by multi-factor cistromic analysis and genetic studies.

Nephron progenitor number determines nephron endowment; a reduced nephron count is linked to the onset of kidney disease. Several transcriptional regulators including Six2, Wt1, Osr1, Sall1, Eya1, Pax2, and Hox11 paralogues are required for specification and/or maintenance of nephron progenitors. However, little is known about the regulatory intersection of these players. Here, we have mapped nephron progenitor-specific transcriptional networks of Six2, Hoxd11, Osr1, and Wt1. We identified 373 multi-factor associated \u27regulatory hotspots\u27 around genes closely associated with progenitor programs. To examine their functional significance, we deleted \u27hotspot\u27 enhancer elements for Six2 and Wnt4. Removal of the distal enhancer for Six2 leads to a ~40% reduction in Six2 expression. When combined with a Six2 null allele, progeny display a premature depletion of nephron progenitors. Loss of the Wnt4 enhancer led to a significant reduction of Wnt4 expression in renal vesicles and a mildly hypoplastic kidney, a phenotype also enhanced in combination with a Wnt4 null mutation. To explore the regulatory landscape that supports proper target gene expression, we performed CTCF ChIP-seq to identify insulator-boundary regions. One such putative boundary lies between the Six2 and Six3 loci. Evidence for the functional significance of this boundary was obtained by deep sequencing of the radiation-induced Brachyrrhine (Br) mutant allele. We identified an inversion of the Six2/Six3 locus around the CTCF-bound boundary, removing Six2 from its distal enhancer regulation, but placed next to Six3 enhancer elements which support ectopic Six2 expression in the lens where Six3 is normally expressed. Six3 is now predicted to fall under control of the Six2 distal enhancer. Consistent with this view, we observed ectopic Six3 in nephron progenitors. 4C-seq supports the model for Six2 distal enhancer interactions in wild-type and Br/+ mouse kidneys. Together, these data expand our view of the regulatory genome and regulatory landscape underpinning mammalian nephrogenesis

Phylogenetic Relationships of Monocots Based on the Highly Informative Plastid Gene ndhF

We used ndhF sequence variation to reconstruct relationships across 282 taxa representing 78 monocot families and all 12 orders. The resulting tree is highly resolved and places commelinids sister to Asparagales, with both sister to Liliales—Pandanales in the strict consensus; Pandanales are sister to Dioscoreales in the bootstrap majority-rule tree, just above Petrosaviales. Acorales are sister to all other monocots, with Alismatales sister to all but Acorales. Relationships among the four major clades of commelinids remain unresolved. Relationships within orders are consistent with those based on rbcL, alone or in combination with atpB and 18S nrDNA, and generally better supported: ndhF contributes more than twice as many informative characters as rbcL, and nearly as many as rbcL, atpB, and 18S nrDNA combined. Based on functional arguments, we hypothesized that net venation and fleshy fruits should both evolve—and thus undergo concerted convergence—in shaded habitats, and revert to parallel venation and dry, passively dispersed fruits in open, sunny habitats. Our data show that net venation arose at least 26 times and disappeared 9 times, whereas fleshy fruits arose 22 times and disappeared 11 times. Both traits arose together at least 15 times and disappeared together 5 times. They thus show a highly significant pattern of concerted convergence (P \u3c 10-9) and are each even more strongly associated with shaded habitats (P \u3c 10-10 to 10-23); net venation is also associated, as predicted, with broad-leaved aquatic plants. Exceptions to this pattern illustrate the importance of other selective constraints and phylogenetic inertia

Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial

IMPORTANCE: Immune dysregulation contributes to poorer outcomes in COVID-19. OBJECTIVE: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021. INTERVENTIONS: Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day). MAIN OUTCOMES AND MEASURES: The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale. RESULTS: Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies. CONCLUSIONS AND RELEVANCE: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04593940