3,294 research outputs found
Design of Phase II cancer trials evaluating survival probabilities
BACKGROUND: Phase II cancer studies are undertaken to assess the activity of a new drug or a new treatment regimen. Activity is sometimes defined in terms of a survival probability, a binary outcome such as one-year survival that is derived from a time-to-event variable. Phase II studies are usually designed with an interim analysis so they can be stopped if early results are disappointing. Most designs that allow for an interim look are not appropriate for monitoring survival probabilities since many patients will not have enough follow-up by the time of the interim analysis, thus necessitating an inconvenient suspension of accrual while patients are being followed. METHODS: Two-stage phase II clinical trial designs are developed for evaluating survival probabilities. These designs are compared to fixed sample designs and to existing designs developed to monitor binomial probabilities to illustrate the expected reduction in sample size or study length possible with the use of the proposed designs. RESULTS: Savings can be realized in both the duration of accrual and the total study length, with the expected savings increasing as the accrual rate decreases. Misspecifying the underlying survival distribution and the accrual rate during the planning phase can adversely influence the operating characteristics of the designs. CONCLUSION: Two-stage phase II trials for assessing survival probabilities can be designed that do not require prolonged suspension of patient accrual. These designs are more efficient than single stage designs and more practical than existing two-stage designs developed for binomial outcomes, particularly in trials with slow accrual
Mixed mode assessment: a preliminary evaluation
This paper examines the usefulness of a combination of self, peer and tutor (mixed mode) assessment of group presentations for promoting deep learning and enhancing the learning experience of students undertaking the first year topic Aust 1004 - An Introduction to Aboriginal Studies, part of the Indigenous minor at Flinders University. It discusses the relative advantages and disadvantages of the three assessment processes and argues that a combination of all three can create an environment to promote deep learning. It evaluates the experiences of 25 first year students using this process and finds that deep learning is enhanced by mixed mode assessment
Incidence of tricyclic antidepressant-like complications after cyclobenzaprine overdose
Background: The cyclobenzaprine structure is similar to amitriptyline; however, tricyclic antidepressant (TCA)-like wide complex dysrhythmia has not been reported. Our objective was to determine the incidence of TCA-like effects in cyclobenzaprine overdoses as reported to 6 poison centers for 2 years. We compared the incidence of these effects to amitriptyline overdoses collected during the same period.
Methods: We performed a retrospective review of 2 years of cases as reported to the Texas Poison Center Network. We identified sole ingestions of cyclobenzaprine and of amitriptyline. Cases had a recorded clinical outcome and clinical effect. A trained reviewer used a standard data collection sheet within a secured electronic database. One investigator audited a random sample of charts.
Results: We identified 3974 cases of cyclobenzaprine calls. Of these, we collected 209 cases of acute overdoses without coingestions. There were no deaths. No cases of cyclobenzaprine ingestions were reported to have died or have a wide QRS or ventricular dysrhythmia. Seizures were reported in 2 cases; however, both were unrelated to cyclobenzaprine. Hypotension was reported in 1.4% (3/209) of cases, and a vasopressor was used in one case (0.5%). Patients with an amitriptyline overdose were more likely to have seizure, coma, tachycardia, a wide QRS or ventricular dysrhythmia, and have received sodium bicarbonate or be intubated.
Conclusions: Cyclobenzaprine overdoses were not reported to cause widened QRS, ventricular dysrhythmias, or seizures, and hypotension was rarely reported. Tricyclic antidepressant-related effects occurred more often in our comparison group of amitriptyline overdoses
Cattail Invasion of Sedge/Grass Meadows in Lake Ontario: Photointerpretation Analysis of Sixteen Wetlands over Five Decades
Photointerpretation studies were conducted to evaluate vegetation changes in wetlands of Lake Ontario and the upper St. Lawrence River associated with regulation of water levels since about 1960. The studies used photographs from 16 sites (four each from drowned river mouth, barrier beach, open embayment, and protected embayment wetlands) and spanned a period from the 1950s to 2001 at roughly decadal intervals. Meadow marsh was the most prominent vegetation type in most wetlands in the late 1950s when water levels had declined following high lake levels in the early 1950s. Meadow marsh increased at some sites in the mid-1960s in response to low lake levels and decreased at all sites in the late 1970s following a period of high lake levels. Typha increased at nearly all sites, except waveexposed open embayments, in the 1970s. Meadow marsh continued to decrease and Typha to increase at most sites during sustained higher lake levels through the 1980s, 1990s, and into 2001. Most vegetation changes could be correlated with lake-level changes and with life-history strategies and physiological tolerances to water depth of prominent taxa. Analyses of GIS coverages demonstrated that much of the Typha invasion was landward into meadow marsh, largely by Typha Ă— glauca. Lesser expansion toward open water included both T. Ă— glauca and T. angustifolia. Although many models focus on the seed bank as a key component of vegetative change in wetlands, our results suggest that canopy-dominating, moisture- requiring Typha was able to invade meadow marsh at higher elevations because sustained higher lake levels allowed it to survive and overtake sedges and grasses that can tolerate periods of drier soil conditions
Molecular Oncology Testing in Resource-Limited Settings
Cancer prevalence and mortality are high in developing nations, where resources for cancer control are inadequate. Nearly one-quarter of cancers in resource-limited nations are infection related, and molecular assays can capitalize on this relationship by detecting pertinent pathogen genomes and human gene variants to identify those at highest risk for progression to cancer, to classify lesions, to predict effective therapy, and to monitor tumor burden over time. Prime examples are human papillomavirus in cervical neoplasia, Helicobacter pylori and Epstein-Barr virus in gastric adenocarcinoma and lymphoma, and hepatitis B or C virus in hepatocellular cancer. Research is underway to engineer devices that overcome social, economic, and technical barriers limiting effective laboratory support. Additional challenges include an educated workforce, infrastructure for quality metrics and record keeping, and funds to sustain molecular test services. The combination of well-designed interfaces, novel and robust electrochemical technology, and telemedicine tools will promote adoption by frontline providers. Fast turnaround is crucial for surmounting loss to follow-up, although increased use of cell phones, even in rural areas, enhances options for patient education and engagement. Links to a broadband network facilitate consultation and centralized storage of medical data. Molecular technology shows promise to address gaps in health care through rapid, user-friendly, and cost-effective devices reflecting clinical priorities in resource-poor areas
Rural women and the works progress program : a partial analysis of levels of living
Publication authorized April 15, 1937."The Agricultural Experiment Station, University of Missouri and the Rural Research Section, Division of Social Research, the Federal Works Progress Administration cooperating.
Effects of the Selective GSK3B Inhibitor, Tideglusib, on Ethanol Consumption, Anxiety-like Behavior, Taste Preference, and Downstream Proteins
Background: We have shown modulations in glycogen synthase kinase 3 beta (GSK3B) abundance or activity regulate ethanol consumption, suggesting potential as a therapeutic target for alcohol use disorder (AUD). Here we report the GSK3B inhibitor tideglusib’s actions on ethanol consumption, basal behaviors, and modulation of GSK3B targets.
Methods: C57BL/6J males and females received i.g. 200mg/kg tideglusib, except drinking-in-the-dark (males;100mg/kg i.p.). Drinking-in-the-dark (DID): Mice given 20% ethanol 4-hours, 4-days/week x 3 weeks and then i.p. tideglusib or vehicle x 4 days in a Latin Square design with ethanol consumption measured daily. Light/Dark Box: Mice gavaged with tideglusib or vehicle and i.p. injected with 1.8g/kg ethanol or saline then tested for 10-min. Taste Preference: Mice received tideglusib x 6 days and then tested daily for saccharin or quinine taste preference. Western Blots: Mice received tideglusib or vehicle i.g. 3x/week for 2-weeks and mPFC assayed for phosphorylated and total GSK3B, Dynamin1, and PSD-95.
Results: Tideglusib decreased ethanol DID consumption, transiently increased locomotion, and had no effect on anxiety-like behaviors or taste preference. Only total Dynamin1 showed tideglusib-induced modulation where females had increased Dynamin1 and decreased pDynamin1/total Dynamin1.
Conclusion: Tideglusib is a promising AUD therapeutic, rapidly decreasing ethanol consumption in a binge-drinking model. Tideglusib is likely not reducing consumption by altering taste or anxiety-like behaviors. Dynamin1 is integral in activity-dependent bulk endocytosis and requires GSK3B-induced rephosphorylation. Tideglusib increased Dynamin1 levels likely represent a compensatory response to decreased GSK3B activity, providing insight to tideglusib’s mechanism in ethanol behaviors. Funded by NIAAA grant R01AA027581.https://scholarscompass.vcu.edu/gradposters/1177/thumbnail.jp
THE CHANDRA VARIABLE GUIDE STAR CATALOG
Variable stars have been identified among the optical-wavelength light curves of guide stars used for pointing control of the Chandra X-ray Observatory. We present a catalog of these variable stars along with their light curves and ancillary data. Variability was detected to a lower limit of 0.02 mag amplitude in the 4000-10000 Ă… range using the photometrically stable Aspect Camera on board the Chandra spacecraft. The Chandra Variable Guide Star Catalog (VGUIDE) contains 827 stars, of which 586 are classified as definitely variable and 241 are identified as possibly variable. Of the 586 definite variable stars, we believe 319 are new variable star identifications. Types of variables in the catalog include eclipsing binaries, pulsating stars, and rotating stars. The variability was detected during the course of normal verification of each Chandra pointing and results from analysis of over 75,000 guide star light curves from the Chandra mission. The VGUIDE catalog represents data from only about 9 years of the Chandra mission. Future releases of VGUIDE will include newly identified variable guide stars as the mission proceeds. An important advantage of the use of space data to identify and analyze variable stars is the relatively long observations that are available. The Chandra orbit allows for observations up to 2 days in length. Also, guide stars were often used multiple times for Chandra observations, so many of the stars in the VGUIDE catalog have multiple light curves available from various times in the mission. The catalog is presented as both online data associated with this paper and as a public Web interface. Light curves with data at the instrumental time resolution of about 2 s, overplotted with the data binned at 1 ks, can be viewed on the public Web interface and downloaded for further analysis. VGUIDE is a unique project using data collected during the mission that would otherwise be ignored. The stars available for use as Chandra guide stars are generally 6-11 mag and are commonly spectral types A and later. Due to the selection of guide stars entirely for positional convenience, this catalog avoids the possible bias of searching for variability in objects where it is to be expected. Statistics of variability compared to spectral type indicate the expected dominance of A-F stars as pulsators. Eclipsing binaries are consistently 20%-30% of the detected variables across all spectral types.United States. National Aeronautics and Space Administration (Smithsonian Astrophysical Observatory. Contract NAS8-03060)United States. National Aeronautics and Space Administration (Smithsonian Astrophysical Observatory. Contract SV3-73016
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