Relative Importance Of Individual Components Research Articles

Results of the COMPASS Trial Analyzed Using Win Ratio Compared With Conventional Analytic Approaches

BackgroundWin ratio (WR) is a newer analytic approach for trials with composite end points that accounts for the relative importance of individual components. Our objective was to compare the results of the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial analyzed using WR with those obtained using conventional statistical approaches. MethodsWe used an unmatched WR analysis for first and total (first plus recurrent) events to examine effects of rivaroxaban with aspirin and rivaroxaban alone vs aspirin alone on primary efficacy (cardiovascular death, stroke, myocardial infarction), safety (modified International Society on Thrombosis and Haemostasis major bleeding), and net clinical benefit (primary efficacy plus fatal or critical organ bleeding) end points. We compared the WR results with those obtained using the Cox proportional hazards regression model for first events and Anderson-Gill method for total events. We calculated the win difference to estimate absolute treatment effects. ResultsThe WR approach produced results consistent with those obtained using conventional statistical methods for the primary composite end point (first event: WR, 1.32 [95% confidence interval (CI), 1.14-1.52]; 1/Cox hazard ratio, 1.32 [95% CI, 1.16-1.52]; total [first plus recurrent] events: WR, 1.32 [95% CI, 1.14-1.52]; 1/Anderson-Gill hazard ratio, 1.32 [95% CI, 1.16-1.54]) as well as for main safety and net clinical benefit end points. The absolute benefits of the combination of rivaroxaban and aspirin compared with aspirin alone calculated using the win difference were greatest in those with multiple high-risk features. ConclusionsReanalysis of the COMPASS trial results using WR produced results that were consistent with those obtained using conventional statistical approaches. Clinical Trial RegistrationNCT01776424

Interim monitoring in a treatment strategy trial with a composite primary endpoint

When a clinical trial has a composite endpoint and a comparison of treatment strategies with multiple intervention components, interim data reviews by a data safety and monitoring board (DSMB) can be challenging as the data evolve on multiple fronts. We illustrate with a study in the treatment of Kaposi sarcoma (KS), an HIV-associated cancer with a multi-faceted disease presentation. The study, ACTG-A5264/AMC-067, was a 1:1 randomized trial to compare two strategies: immediate initiation of etoposide with antiretroviral therapy (ART), or ART with delayed etoposide upon disease progression. The outcome was a composite endpoint that included the following events, ordered from worst to best in the following three categories: (1) KS progression at 48 weeks, death, initiation of alternate KS treatment, loss to study follow-up; (2) stable KS; and (3) partial or complete KS response at 48 weeks. We present the interim results on the composite endpoint and the individual components, where components favored different study arms at an interim review. To facilitate interim data monitoring for complex trials, we recommend clear communications between the study team and the DSMB prior to the initiation of the trial on the need for a composite endpoint, the intentions behind the defined strategies, and relative importance of individual components of the composite endpoint. We also recommend flexibility in the timing of data reviews by the DSMB to interpret emerging data in multiple dimensions.Clinicaltrials.govNCT01352117

Symposium review: Selection for fertility in the modern dairy cow—Current status and future direction for genetic selection

The establishment of pregnancy following insemination is the primary definition of fertility in most dairy systems. Highly fertile cows establish pregnancy sooner after calving and require fewer inseminations than lower-fertility cows. Pregnancy occurs through a series of individual events in sequence. In postpartum cows, for example, the uterus involutes, estrous cycles are re-established, estrus is expressed and detected, sperm are deposited in the reproductive tract and capacitate, ovulation occurs and is followed by fertilization, and the corpus luteum forms and produces sufficient progesterone to maintain pregnancy. The oviduct supports early cleavage and the uterus establishes a receptive environment for the developing pregnancy. Each individual event is theoretically heritable and these events collectively contribute to the phenotype of pregnancy after insemination. Across most dairy systems, genetic selection for fertility in cows is primarily based on reduced days from calving to pregnancy (i.e., days open). Dairy systems differ with respect to reproductive management applied to cows, which may affect the relative importance of individual components to the overall fertility of the cow. In some systems, cows are inseminated after detected estrus with minimal intervention. In these systems, days open effectively captures the summation of the individual components of fertility. More intensive systems use hormonal treatments (e.g., PGF2α, GnRH) followed by timed artificial insemination (AI). Timed AI does not invalidate days open but the individual components that contribute to days open may be more or less important. Selection of cows for days open within populations that are managed differently may place different pressures on the individual components of fertility. Ensuring uniform performance of future cows across a variety of reproductive management systems may require a greater understanding of the underlying genetics of the individual components of fertility.

Enhanced recovery after surgery in colorectal surgery: Impact of protocol adherence on patient outcomes

Study objectivesThere is growing evidence internationally to support Enhanced Recovery After Surgery (ERAS) pathways. The impact of pathway compliance and the relative importance of individual components, however, remains less clear. Our institution implemented a multimodal ERAS protocol for elective colorectal surgery in November 2013. The objectives of this study were to investigate the impact of the introduction of the pathway, the relationship between pathway adherence and patient outcomes, and the relative importance of individual components. DesignThis was a single-center, observational cohort study of elective colorectal surgical patients. SettingA tertiary care and academic teaching hospital in Canada. PatientsProspective data was collected from 495 consecutive major colorectal surgical patients following the ERAS launch. Retrospective data was also collected from a pre-ERAS cohort of 99. MeasurementsAdherence to 12 ERAS components were measured, along with American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP®) defined patient complications and hospital length of stay (LOS). Post-ERAS patients were divided in to two groups: high compliance (≥75% process adherence) and low compliance (<75% adherence). Outcomes were compared between groups. Main resultsThere was a significant reduction in both complication rate (31.5% vs 14.6%; p ≤0.05) and hospital mean LOS (10.1 vs 6.9 days; p ≤0.05) following introduction of the ERAS pathway. The high adherence group had a shorter mean LOS (5.7 vs 8.6 days; p ≤0.01) and lower rate of complications (11.2% vs 19.6%; p = 0.02) compared with the low compliance group. ConclusionsHigher adherence to the standardized ERAS protocol was associated with improved patient outcomes, including reduced pulmonary complications. The cause-effect relationship is complex and likely influenced by confounding factors. Our data provides feedback to aid ongoing innovation of our pathway locally and adds to the growing body of evidence supporting the value of ERAS in general.

Energy-balance mechanisms underlying consistent large-scale temperature responses in warm and cold climates

Climate simulations show consistent large-scale temperature responses including amplified land–ocean contrast, high-latitude/low-latitude contrast, and changes in seasonality in response to year-round forcing, in both warm and cold climates, and these responses are proportional and nearly linear across multiple climate states. We examine the possibility that a small set of common mechanisms controls these large-scale responses using a simple energy-balance model to decompose the temperature changes shown in multiple lgm and abrupt4 × CO 2 simulations from the CMIP5 archive. Changes in the individual components of the energy balance are broadly consistent across the models. Although several components are involved in the overall temperature responses, surface downward clear-sky longwave radiation is the most important component driving land–ocean contrast and high-latitude amplification in both warm and cold climates. Surface albedo also plays a significant role in promoting high-latitude amplification in both climates and in intensifying the land–ocean contrast in the warm climate case. The change in seasonality is a consequence of the changes in land–ocean and high-latitude/low-latitude contrasts rather than an independent temperature response. This is borne out by the fact that no single component stands out as being the major cause of the change in seasonality, and the relative importance of individual components is different in cold and warm climates.

On the Relative Importance of Individual Components of Chord Recognition Systems

Most chord recognition systems share a common architecture comprising two main stages: feature extraction and pattern matching, and two optional sub stages: pre-filtering and post-filtering. Understanding the interaction between these basic components is very important not only for achieving optimal performance, but also for assessing the potential and limitations of the system. Unfortunately, there are no studies that sufficiently evaluate the effects of the different approaches to each processing step and the interactions between these steps. In this paper we attempt to remedy this deficiency by performing a systematic evaluation encompassing a wide variety of techniques used for each processing step. In our study we find that filtering has a significant impact on performance, but providing musical context information in the transition matrix is rendered moot by the need to enforce continuity in the estimations. We discovered that the benefits of using complex chord models can be largely offset by an appropriate choice of features. In addition, the initial performance gap between different features were not fully compensated by any subsequent processing stages.

Antimicrobial impact of the components of essential oil of Litsea cubeba from Taiwan and antimicrobial activity of the oil in food systems

Using natural additives to preserve foods has become popular due to consumer demands for nature and safety. Antimicrobial activity is one of the most important properties in many plant essential oils (EOs). The antimicrobial activity of the essential oil of Litsea cubeba (LC-EO) from Taiwan and the antimicrobial impact of individual volatile components in the oil on pathogens or spoilage microorganisms: Vibrio parahaemolyticus, Listeria monocytogenes, Lactobacillus plantarum, and Hansenula anomala in vitro, and the antimicrobial activity of the LC-EO against these organisms in food systems were studied. The “antimicrobial impact” (AI) is a new term that combines the effects of minimal microbicidal concentration (MMC) and quantity of an antimicrobial substance. The AI can quantitatively reflect the relative importance of individual components of the EO on the entire antimicrobial activity of the EO. The MMCs of the LC-EO against V. parahaemolyticus, L. monocytogenes, L. plantarum, and H. anomala were determined as 750, 750, 1500, and 375μg/g, respectively in vitro. The MMCs of the LC-EO were 3000, 6000, and 12,000μg/g for L. monocytogenes in tofu stored at 4°C, 25°C, and 37°C, respectively. The temperature affected the bacterial growth which consequently influenced the MMCs of the LC-EO. The MMCs of the LC-EO were 3000, 6000, and 375μg/g for Vibrio spp. in oysters, L. plantarum in orange–milk beverage, and H. anomala in soy sauce, respectively. Except for soy sauce, the food systems exhibited marked matrix effects on diminishing the antimicrobial activity of the LC-EO. Averagely, citral accounted for ca 70% of the total AI value for all the tested organisms, and the rest of the AI value of the LC-EO was determined by all the tested compounds (ca 4%) and the unidentified compounds (ca 26%).

Survey of ICU Physicians Regarding Components of Daily ICU Goal Sheet

PURPOSE: Since buy-in of end-users is integral to the success of checklists, we conducted a web-based survey to query physicians regarding the relative importance of individual components of various checklists. We wanted to create an end-user defined minimum set of high utility components which could be used as the basis of a daily ICU checklist.

Correlations for mass transfer from a liquid spill: Comparisons and recommendations

Accurate estimation of mass evaporation from a liquid spill is of great concern in the area of hazard analysis. The chemical properties, especially its boiling point with respect to ambient temperature, play a major role in the result of evaporation rate. Many models have been proposed for estimating evaporation rate from a boiling or evaporating pool. The objective of this article is to apply the proposed correlations to good quality pool evaporation data and compare their accuracy. Based on current analysis, we recommend the use of the Churchill model for pool evaporation. This model applies to the range of flow regimes from laminar to turbulent. The model provides convective mass and heat transfer coefficients for a complete range of Re, Pr, and Sc. We also present the individual heat sources forming the pool heat budget to get a feel for the relative importance of individual components in pool evaporation. © 2011 American Institute of Chemical Engineers Process Saf Prog, 2011.

An evaluation of graduated driver licensing programs in North America using a meta-analytic approach

Most jurisdictions in North America have some version of graduated driver licensing (GDL). A sound body of evidence documenting the effectiveness of GDL programs in reducing collisions, fatalities and injuries among novice drivers is available. However, information about the relative importance of individual components of GDL is lacking. The objectives of this study are to calculate a summary statistic of GDL effectiveness and to identify the most effective components of GDL programs using a meta-analytic approach. Data from 46 American States, the District of Columbia and 11 Canadian jurisdictions are used and were obtained from the Fatality Analysis Reporting System (FARS) for the U.S. and from Transport Canada's Traffic Accident Information Database (TRAID) for Canada. The timeframe of this evaluation is 1992 through 2006, inclusive. Relative fatality risks and their 95% confidence intervals were calculated using fatality counts and population data for target and comparison groups, both in a pre-implementation and post-implementation period in each jurisdiction. The target groups were 16-, 17-, 18- and 19-year-old drivers. The comparison group was 25–54-year-old drivers. The relative fatality risks of all jurisdictions were summarized using the random effects DerSimonian and Laird model. Meta-regression using Restricted Maximum Likelihood (REML) and Markov Chain Monte Carlo (MCMC) Gibbs sampling was also conducted. Strong evidence in support of GDL was found. GDL had a positive and significant impact on the relative fatality risk of 16-year-old drivers (reduction of 19.1%). Significant effects were found for meta-regression models with 16-, 18- and 19-year-old drivers. These effects include length of night restriction in the learner stage, country, driver education in the learner stage and in the intermediate stage, whether night restrictions are lifted in the intermediate stage for work purposes, passenger restriction in the intermediate stage, whether passenger restrictions in the intermediate stage are lifted if passengers are family members, and whether there is an exit test in the intermediate stage. In conclusion, several GDL program components have an important effect on the relative fatality risk of novice drivers. These results help understand how such effects are achieved.

Anomalous dynamics of cell migration

Cell movement--for example, during embryogenesis or tumor metastasis--is a complex dynamical process resulting from an intricate interplay of multiple components of the cellular migration machinery. At first sight, the paths of migrating cells resemble those of thermally driven Brownian particles. However, cell migration is an active biological process putting a characterization in terms of normal Brownian motion into question. By analyzing the trajectories of wild-type and mutated epithelial (transformed Madin-Darby canine kidney) cells, we show experimentally that anomalous dynamics characterizes cell migration. A superdiffusive increase of the mean squared displacement, non-Gaussian spatial probability distributions, and power-law decays of the velocity autocorrelations is the basis for this interpretation. Almost all results can be explained with a fractional Klein-Kramers equation allowing the quantitative classification of cell migration by a few parameters. Thereby, it discloses the influence and relative importance of individual components of the cellular migration apparatus to the behavior of the cell as a whole.

THE FOULING AND CLEANING OF ULTRAFILTRATION MEMBRANES DURING THE FILTRATION OF MODEL TEA COMPONENT SOLUTIONS

ABSTRACT Proteins and polyphenols are the principal fouling constituents in the ultrafiltration (UF) of black tea liquor. The aim of this study was to determine the relative importance of individual components in the fouling process, to investigate any synergetic interactions that were occurring and to compare the cleaning characteristics of different fouled membranes. A 30‐kD molecular weight cutoff polysulfone UF membrane in dead‐end mode was challenged with model solutions of tea components. Model solutions consisted of tea proteins, theaflavins (TFs), thearubigins and caffeine. Sodium hydroxide was used as a cleaning reagent. Permeate flux decline curves were presented for single components and mixtures. Individual component transfer fluxes and rejections were also presented. An unexpected finding was that protein in a mixture with TFs could permeate the membrane to a degree, while a protein solution in the absence of the polyphenol was completely rejected. The inspection of membranes fouled by different solutions revealed different foulant morphologies. Membrane cleaning with 0.2 wt % sodium hydroxide was generally found to be effective.

Short-term cocaine treatment causes neuroadaptive changes in Galphaq and Galpha11 proteins in rats undergoing withdrawal.

One of the characteristics of drug dependence is that a drug has to be administered repeatedly before withdrawal effects can be observed. We have previously shown that withdrawal after 14 days of cocaine treatment produces a supersensitivity of hypothalamic 5-hydroxytryptamine (serotonin) 2A (5-HT(2A)) receptors, which is accompanied by increases in the levels of Galpha(q) and Galpha(11) proteins. Unfortunately, the exact duration of cocaine treatment necessary to induce alterations in G protein levels during cocaine withdrawal is unknown. The present study investigated the minimum cocaine treatment period required to produce changes in protein levels of membrane- and cytosol-associated Galpha(q) and Galpha(11) proteins in the hypothalamic paraventricular nucleus, amygdala, and frontal cortex. Rats were injected with cocaine (15 mg/kg i.p., b.i.d.) for 0, 1, 3, 5, and 7 days and tested after 2 days of withdrawal. The levels of Galpha(q) and Galpha(11) proteins were increased in the paraventricular nucleus and the amygdala but not in the frontal cortex. Although 1 and 3 days of cocaine treatment were sufficient to maximally elevate the protein levels of Galpha(11) and Galpha(q) proteins in the amygdala, 5 days of treatment were required to maximally increase the levels of Galpha(11) and Galpha(q) proteins in the paraventricular nucleus. The data suggest that the amygdala shows a faster neuroadaptation to the effects of cocaine than the hypothalamic paraventricular nucleus. These findings provide insight into the relative importance of individual components of 5-HT(2A) receptor signal transduction system in regulating the overall sensitivity of this signaling in cocaine-treated rats.