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RATIONALE: People with cystic fibrosis (CF) experience acute worsening of respiratory symptoms and lung function known as pulmonary exacerbations. Treatment with intravenous antimicrobials is common; however, there is scant evidence to support a standard treatment duration. OBJECTIVES: To test differing durations of intravenous antimicrobials for CF exacerbations. METHODS: STOP2 (Standardized Treatment of Pulmonary Exacerbations 2) was a multicenter, randomized, controlled clinical trial in exacerbations among adults with CF. After 7–10 days of treatment, participants exhibiting predefined lung function and symptom improvements were randomized to 10 or 14 days’ total antimicrobial duration; all others were randomized to 14 or 21 days’ duration. MEASUREMENTS AND MAIN RESULTS: The primary outcome was percent predicted FEV(1) (ppFEV(1)) change from treatment initiation to 2 weeks after cessation. Among early responders, noninferiority of 10 days to 14 days was tested; superiority of 21 days compared with 14 days was compared for the others. Symptoms, weight, and adverse events were secondary. Among 982 randomized people, 277 met improvement criteria and were randomized to 10 or 14 days of treatment; the remaining 705 received 21 or 14 days of treatment. Mean ppFEV(1) change was 12.8 and 13.4 for 10 and 14 days, respectively, a ‒0.65 difference (95% CI [‒3.3 to 2.0]), excluding the predefined noninferiority margin. The 21- and 14-day arms experienced 3.3 and 3.4 mean ppFEV(1) changes, a difference of ‒0.10 (‒1.3 to 1.1). Secondary endpoints and sensitivity analyses were supportive. CONCLUSIONS: Among adults with CF with early treatment improvement during exacerbation, ppFEV(1) after 10 days of intravenous antimicrobials is not inferior to 14 days. For those with less improvement after one week, 21 days is not superior to 14 days. Clinical trial registered with www.clinicaltrials.gov (NCT02781610).

Using three spatial network measures of “space syntax”, this correlational study describes four interaction-related behaviors among three groups of users in relation to visibility and accessibility of spaces in four adult intensive care units (ICUs) of different size, geometry, and specialty. Systematic field observations of interaction-related behaviors show significant differences in spatial distribution of interaction-related behaviors in the ICUs. Despite differences in unit characteristics and interaction-related behaviors, the study finds that when nurses and physicians “interact while sitting” they prefer spaces that help maintain a high level of environmental awareness, that when nurses “walk” and “interact while walking” they avoid spaces with better global access and visibility, and that everyone in ICUs “walk” more in spaces with higher control over neighboring spaces. It is argued that such consistent behavioral patterns occur due to the structural similarities of spatial networks over and above the more general functional similarities of ICUs.

The objective of the study was to develop instruments for describing and assessing some aspects of design of the primary work areas of nurses and physicians in intensive care units (ICUs). Separate questionnaires for ICU physicians and nurses were developed. Items related to individual- and unit-level design features of the primary work areas of nurses and physicians were organized using constructs found in the literature. Items related to staff satisfaction and staff use of time in relation to primary work area design were also included. All items and constructs were reviewed by experts for content validity and were modified as needed before use. The final questionnaires were administered to a convenience sample of 4 ICUs in 2 large urban hospitals. A total of 55 nurses and 29 physicians completed the survey. The Cronbach α was used to measure internal consistency, and factor analysis was used to provide construct-related validity. Convergent and discriminant validity were assessed through examining bivariate correlations between relevant scales/items. Analysis of variance was used to identify whether the between-group member responses were significant among the 4 units. The Cronbach α values for all except 3 preliminary scales indicated acceptable reliability. Factor analysis indicated that some preliminary scales could be partitioned into subscales for finer descriptions of the primary work areas. Correlational analysis provided strong evidence of convergent and discriminant validity of all the scales and subscales. The significance level of F-statistics showed that the units were significantly different from each other, providing evidence of more between-unit variance than within-unit variance. Therefore, the questionnaires developed in the study offer a promising departure point for rigorous description and evaluation of the primary work areas in relation to staff satisfaction and use of time in ICUs at a time when the importance of such studies is growing.

Introduction Metabolic acidosis and coma are common complications of acetaminophen overdose. These affects are usually attributed to massive hepatic necrosis caused by Nacetyl-p-benzoquinoneimine (NAPQI), a toxic metabolite of acetaminophen. We describe an unusual case of lactic acidosis and coma in a patient with acetaminophen toxicity without associated hepatocellular damage as the identifiable cause.

We develop a series expansion for the calculation of the magnetic field near the center of Helmholtz coils and apply the result to a magnet of our design. Our analysis considers geometric details of the coils, the magnetic properties of the form and windings, conductor insulation effects, and several winding imperfections. We also consider the relaxation of coil symmetry which happens when the mean radius of each coil and the coil midplane separation distance are unequal. We compute the field uniformity near the coil's center for three cases, including one where axial symmetry remains but geometric imperfections of the order of 10(-3) of the coil "radius" exist.

The mitotic inhibitor, chloral hydrate, induces ciliary loss in the early embryo phase of Lytechinus pictus. It causes a breakdown of cilia at the junction of the cilium and the basal body known as the basal plate. This leaves the plasma membrane temporarily unsealed. The basal apparatus accessory structures, consisting of the basal body, basal foot, basal foot cap, striated side arm, and striated rootlet, are either misaligned or disintegrated by treatment with chloral hydrate. Furthermore, microtubules which are associated with the basal apparatus are disassembled. Mitochondria accumulate at the base of cilia - underneath the plasma membrane - and show alterations in their structural organization. The accumulation of mitochondria is observed in 40% of all electron micrograph sections while 60% show the areas mostly devoid of mitochondria. The microvilli surrounding a cilium and striated rootlet remain intact in the presence of chloral hydrate. These results suggest that deciliation in early sea urchin embryos by chloral hydrate is caused by combined effects on the ciliary membrane and on microtubules in the cilia. Furthermore, it is suggested that chloral hydrate can serve as a tool to explore the cytoskeletal mechanisms that are involved in cilia motility in the developing sea urchin embryo.

Cancer is a disease characterized by uncontrolled cell divisions in which the molecular controls for cytoskeletal regulation are bypassed. Cell division is governed by centrosomes, microtubule-organizing cell organelles which are crucial for the organization of the mitotic apparatus during mitosis and cell division. Because centrosome abnormalities are observed in the most common human cancers, we used immunofluorescence and transmission electron microscopy to determine centrosome organization in the human androgenresponsive prostate cancer cell line LNCaP and the androgen-independent prostate cancer cell line DU145. During interphase, centrosomes are located in close vicinity to the outer nuclear membrane, duplicate during S-phase, and become separated to the mitotic poles during the transition from interphase to mitosis. Centrosome regulation is based on a number of different factors which are only partly understood. Hormones play a role during developmental regulation of prostates which might trigger the activation of centrosome proteins and consequent cell divisions in order to ensure tissue growth.

Sea urchins have been used for over a century as a remarkable animal model system in which to study cell, molecular, and developmental biology. The studies presented here have used sea urchin eggs and embryos for pioneering experiments to explore the effects of microgravity on the cytoskeleton during a space flight on the space shuttle Endeavor. The culture conditions followed those described previously utilizing the Aquatic Research Facility (ARF) to fertilize and culture eggs and embryos up to the pluteus stage under controlled temperature (12°C) and fixation conditions. To achieve a final fixation with 0.5% glutaraldehyde and 4μM taxol, concentrated fixation fluid was injected at preselected time points to preserve microtubules, centrioles, centrosomes, microfilaments, mitochondria, and cell membranes.The analysis of the results revealed that the centriole-centrosome complex during cell division and cilia formation showed alterations in samples that had been exposed to microgravity while control cells cultured in a centrifuge at lg in space and those cultured on ground appeared normal.