PREDICTING THE USABILITY OF ALPHANUMERIC DISPLAYS

A review of the literature on alphanumeric displays, especially computer-generated displays, suggests that four basic characteristics of display formats affect how well users can extract information from the displays: (1) Overall density--the number of characters displayed, expressed as a percentage of the total spaces available; (2) Local density--the number of other characters near each character; (3) Grouping--the extent to which characters on the display form well defined perceptual groups; and (4) Layout complexity--the extent to which the arrangement of items on the display follows a predictable visual scheme. Objective ways of measuring these display characteristics have been developed and implemented in a computer program. In Experiment 1, 520 computer-generated displays that varied on these display measures were studied. Search times to locate data items on the diplays were measured as well as subjective ratings of ease of use. Regression equations were developed to predict the search times and subjective ratings using the display measures. The results indicated that both search times (R('2) = .508) and subjective ratings (R('2) = .805) could be predicted quite well. In experiment 2, the regression equations developed in Experiment 1 were used to predict, a priori, search times and subjective ratings for a new set of 150 displays. The regression equations generalized quite well, resulting in high correlations between predicted and actual search times (r = .800) and subjective ratings (r = .799). The regression equations indicate that the most important predictors of search time are two measures associated with the grouping of characters: the number of groups on the display and the average visual angle subtended by those groups. Likewise, the most important predictors of subjective rating are a measure of local density, which is essentially how "tightly packed" the display is, and a measure of layout complexity, which is essentially how well the items on the display are aligned with each other

Fluid mechanics: Fluid statics

If the sum of the external forces acting on a fluid element is zero, the fluid will be at rest or moving as a solid body - in either case, the fluid element is in equilibrium. This section considers fluids in such an equilibrium state. For fluids in equilibrium, the only internal stresses acting will be normal forces because the shear stresses depend on velocity gradients, and all such gradients, by the definition of equilibrium, are zero. If one then carries out a balance between the body forces, assumed proportional to volume or mass - such as gravity - and the normal surface stresses acting on an elementary prismatic fluid volume, the resulting equilibrium equations, after shrinking the volume to zero, show that the normal stresses at a point are the same in all directions; because they are known to be negative, this common value, called the pressure, is denoted by -p

Long-term safety and efficacy of tezacaftor–ivacaftor in individuals with cystic fibrosis aged 12 years or older who are homozygous or heterozygous for Phe508del CFTR (EXTEND): an open-label extension study

Background: Tezacaftor-ivacaftor is an approved cystic fibrosis transmembrane conductance regulator (CFTR) modulator shown to be efficacious and generally safe and well tolerated over 8-24 weeks in phase 3 clinical studies in participants aged 12 years or older with cystic fibrosis homozygous for the Phe508del CFTR mutation (F/F; study 661-106 [EVOLVE]) or heterozygous for the Phe508del CFTR mutation and a residual function mutation (F/RF; study 661-108 [EXPAND]). Longer-term (>24 weeks) safety and efficacy of tezacaftor-ivacaftor has not been assessed in clinical studies. Here, we present results of study 661-110 (EXTEND), a 96-week open-label extension study that assessed long-term safety, tolerability, and efficacy of tezacaftor-ivacaftor in participants aged 12 years or older with cystic fibrosis who were homozygous or heterozygous for the Phe508del CFTR mutation. Methods: Study 661-110 was a 96-week, phase 3, multicentre, open-label study at 170 clinical research sites in Australia, Europe, Israel, and North America. Participants were aged 12 years or older, had cystic fibrosis, were homozygous or heterozygous for Phe508del CFTR, and completed one of six parent studies of tezacaftor-ivacaftor: studies 661-103, 661-106, 661-107, 661-108, 661-109, and 661-111. Participants received oral tezacaftor 100 mg once daily and oral ivacaftor 150 mg once every 12 h for up to 96 weeks. The primary endpoint was safety and 'tolerability. Secondary endpoints were changes in lung function, nutritional parameters, and respiratory symptom scores; pulmonary exacerbations; and pharmacokinetic parameters. A post-hoc analysis assessed the rate of lung function decline in F/F participants who received up to 120 weeks of tezacaftor-ivacaftor in studies 661-106 (F/F) and/or 661-110 compared with a matched cohort of CFTR modulator-untreated historical F/F controls from the Cystic Fibrosis Foundation Patient Registry. Primary safety analyses were done in all participants from all six parent studies who received at least one dose of study drug during this study. This study was registered at ClinicalTrials.gov (NCT02565914). Findings: Between Aug 31, 2015, to May 31, 2019, 1044 participants were enrolled in study 661-110 from the six parent studies of whom 1042 participants received at least one dose of study drug and were included in the safety set. 995 (95%) participants had at least one TEAE; 22 (2%) had TEAEs leading to discontinuation; and 351 (34%) had serious TEAEs. No deaths occurred during the treatment-emergent period; after the treatment-emergent period, two deaths occurred, which were both deemed unrelated to study drug. F/F (106/110; n=459) and F/RF (108/110; n=226) participants beginning tezacaftor-ivacaftor in study 661-110 had improvements in efficacy endpoints consistent with parent studies; improvements in lung function and nutritional parameters and reductions in pulmonary exacerbations observed in the tezacaftor-ivacaftor groups in the parent studies were generally maintained in study 661-110 for an additional 96 weeks. Pharmacokinetic parameters were also similar to those in the parent studies. The annualised rate of lung function decline was 61·5% (95% CI 35·8 to 86·1) lower in tezacaftor-ivacaftor-treated F/F participants versus untreated matched historical controls. Interpretation: Tezacaftor-ivacaftor was generally safe, well tolerated, and efficacious for up to 120 weeks, and the safety profile of tezacaftor-ivacaftor in study 661-110 was consistent with cystic fibrosis manifestations and with the safety profiles of the parent studies. The rate of lung function decline was significantly reduced in F/F participants, consistent with cystic fibrosis disease modification. Our results support the clinical benefit of long-term tezacaftor-ivacaftor treatment for people aged 12 years or older with cystic fibrosis with F/F or F/RF genotypes. Funding: Vertex Pharmaceuticals Incorporated

A genomic catalog of Earth’s microbiomes

The reconstruction of bacterial and archaeal genomes from shotgun metagenomes has enabled insights into the ecology and evolution of environmental and host-associated microbiomes. Here we applied this approach to >10,000 metagenomes collected from diverse habitats covering all of Earth’s continents and oceans, including metagenomes from human and animal hosts, engineered environments, and natural and agricultural soils, to capture extant microbial, metabolic and functional potential. This comprehensive catalog includes 52,515 metagenome-assembled genomes representing 12,556 novel candidate species-level operational taxonomic units spanning 135 phyla. The catalog expands the known phylogenetic diversity of bacteria and archaea by 44% and is broadly available for streamlined comparative analyses, interactive exploration, metabolic modeling and bulk download. We demonstrate the utility of this collection for understanding secondary-metabolite biosynthetic potential and for resolving thousands of new host linkages to uncultivated viruses. This resource underscores the value of genome-centric approaches for revealing genomic properties of uncultivated microorganisms that affect ecosystem processes.</p