Joint modeling of longitudinal outcomes and survival using latent growth modeling approach in a mesothelioma trial

Joint modeling of longitudinal and survival data can provide more efficient and less biased estimates of treatment effects through accounting for the associations between these two data types. Sponsors of oncology clinical trials routinely and increasingly include patient-reported outcome (PRO) instruments to evaluate the effect of treatment on symptoms, functioning, and quality of life. Known publications of these trials typically do not include jointly modeled analyses and results. We formulated several joint models based on a latent growth model for longitudinal PRO data and a Cox proportional hazards model for survival data. The longitudinal and survival components were linked through either a latent growth trajectory or shared random effects. We applied these models to data from a randomized phase III oncology clinical trial in mesothelioma. We compared the results derived under different model specifications and showed that the use of joint modeling may result in improved estimates of the overall treatment effect

Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings

Background:Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.Methods and Findings:1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure.An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39-0.64 for women; HR 0.79, CI 0.62-1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12-2.04; p = 0.007).Conclusion: EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen.Trial Registration:http://www.ClinicalTrials.gov NCT00084136

Moisture and temperature variation in layered soil profile

Non-Peer ReviewedA laboratory experiment was conducted in a clay soil in Saskatoon to study the effect of layering on soil seedbed moisture and temperature variations. The treatments were subjected to a diurnal temperature and relative humidity cycle for seven days. Four layering configurations along with 3 different gravimetric initial moisture contents were investigated. Temperature and moisture content were monitored at 15, 45, 75 and 135 mm depths. Preliminary results showed that layering did not affect temperature variation in the soil profile. Layering proved to be more effective in conserving moisture in lower initial moisture content treatments and in 30 to 60 mm depth

Effect of seedbed packing on canola seedling emergence

Non-Peer ReviewedMany agricultural cultivation equipment produce a stratified seedbed, i.e., made up of layers of soil having different bulk densities, porosities and structure. For example, tillage accomplished using a chisel followed by a roller and a spike tooth harrow will leave the top soil layered. Type of culter, presswheel and orientation of culter and presswheel in a seed drill can affect stratification. It has been reported that in stratified seedbeds moisture is better conserved while still permitting an appropriate soil structure with good seed-soil contact for the early stages of crop growth. It is believed that a layered seedbed reduces the evaporation rate from the top soil by disrupting the continuity of capillary tubes. In this study we propose to investigate the effect of a layered seedbed on seed germination and seedling establishment of canola (Brassica campestris) under controlled conditions. Canola was selected because of its increasing importance in Saskatchewan and world agriculture. Additionally, canola has a poor germination success rate. Since the growing point of canola is above ground, its germination can be easily impeded by soil resistance. It is therefore planted at shallow depths (12-25 mm); however, its minute seed size makes it highly susceptible to temperature and moisture variations in the upper soil layer. Treatments include five stratification levels and four soil moisture contents from 30 to 90% of field capacity in a clay soil. Layer bulk densities are 0.95, 1.2 and 1.4 Mg/m3 for loose, bottom and dense horizons, respectively. Ambient temperature is controlled at two discrete levels (5” C, 15” C) over each 24 hour period. Soil moisture content and temperature are monitored at four different depths. Tests are of ten days duration at the end of which percent seed germination and seedling emergence are determined. One of the major challenges associated with this study is the measurement of soil moisture. Three types of sensors were compared: an aluminum fiber-glass sensor (Model MC-300, Soiltest Inc., Lake Bluff, IL), resistance based parallel steel probes and a small (9 x 15 x 17 mm) plaster of Paris ‘gypsum block’ made by the authors. For the small scale experiment here the first two types of sensors proved unsatisfactory, largely because of particle contact and size considerations. The gypsum block showed a satisfactory response to soil moisture changes in the soil, even in the very loose layer, and because of its small size comes to equilibrium in a relatively short time. Preliminary experiments showed significantly different drying rates, germination rates and seedling emergence in different treatments