Summary Background Antiangiogenic agents have established efficacy in the treatment of metastatic colorectal cancer. We investigated whether bevacizumab could improve disease-free survival in the ...adjuvant setting after resection of the primary tumour. Methods For the open-label, randomised, controlled QUASAR 2 trial, which was done at 170 hospitals in seven countries, we recruited patients aged 18 years or older with WHO performance status scores of 0 or 1 who had undergone potentially curative surgery for histologically proven stage III or high-risk stage II colorectal cancer. Patients were randomly assigned (1:1) to receive eight 3-week cycles of oral capecitabine alone (1250 mg/m2 twice daily for 14 days followed by a break for 7 days) or the same regimen of oral capecitabine plus 16 cycles of 7·5 mg/kg bevacizumab by intravenous infusion over 90 min on day 1 of each cycle. Randomisation was done by a computer-generated schedule with use of minimisation with a random element stratified by age, disease stage, tumour site, and country. The study was open label and no-one was masked to treatment assignment. The primary endpoint was 3-year disease-free survival, assessed in the intention-to-treat population. Toxic effects were assessed in patients who received at least one dose of randomised treatment. This trial is registered with the ISRCTN registry, number ISRCTN45133151. Findings Between April 25, 2005, and Oct 12, 2010, 1952 eligible patients were enrolled, of whom 1941 had assessable data (968 in the capecitabine alone group and 973 in the capecitabine and bevacizumab group). Median follow-up was 4·92 years (IQR 4·00–5·16). Disease-free survival at 3 years did not differ between the groups (75·4%, 95% CI 72·5–78·0 in the capecitabine and bevacizumab group vs 78·4%, 75·7–80·9 in the capecitabine alone group; hazard ratio 1·06, 95% CI 0·89–1·25, p=0·54). The most common grade 3–4 adverse events were hand–foot syndrome (201 21% of 963 in the capecitabine alone group vs 257 27% of 959 in the capecitabine and bevacizumab group) and diarrhoea (102 11% vs 104 11%), and, with the addition of bevacizumab, expected increases were recorded in all-grade hypertension (320 33% vs 75 8%), proteinuria (197 21% vs 49 5%), and wound healing problems (30 3% vs 17 2%). 571 serious adverse events were reported (221 with capecitabine alone and 350 with capecitabine and bevacizumab). Most of these were gastrointestinal (n=245) or cardiovascular (n=169). 23 deaths within 6 months of randomisation were classified as being related to treatment, eight in the capecitabine alone group and 15 in the capecitabine and bevacizumab group. Interpretation The addition of bevacizumab to capecitabine in the adjuvant setting for colorectal cancer yielded no benefit in the treatment of an unselected population and should not be used. Funding Roche.
AbstractThree independent analyses establish that the Conestoga River flow published by the U.S. Geological Survey (USGS) for Tropical Storm Agnes in 1972 of 1,420 m3/s (50,300 ft3/s) should have ...been at least 1,660 m3/s (58,600 ft3/s), an increase of over 16%. The three analyses included an empirical analysis of the data for U.S. Geological Survey Gauge 01576500, a reanalysis of a 1978 U.S. Army Corp of Engineers Hydrologic Engineering Center (HEC)-2 simulation of the Conestoga River, and a retrofit and minor corrections to a preliminary 2013 HEC-RAS (river analysis system) simulation of the Conestoga River.
Movie producers are often reluctant to cast more than a few minority actors in otherwise race‐neutral movies for fear that the White audience will largely avoid such films. Two experiments were ...conducted to test the idea that the racial makeup of a cast could influence White audiences' selective exposure to movies. Results revealed that actors' race does influence selective exposure in certain contexts. For nonromantic movies, participants' racial attitudes moderated the relationship between race and selective exposure. For romantic movies, regardless of racial attitudes, White participants showed significantly less interest in seeing movies with mostly Black casts than in seeing movies with mostly White casts. These findings are discussed in light of both social identity theory and social cognitive theory.
The possibility of a reduced Atlantic thermohaline circulation in response to increases in greenhouse-gas concentrations has been demonstrated in a number of simulations with general circulation ...models of the coupled ocean-atmosphere system. But it remains difficult to assess the likelihood of future changes in the thermohaline circulation, mainly owing to poorly constrained model parameterizations and uncertainties in the response of the climate system to greenhouse warming. Analyses of past abrupt climate changes help to solve these problems. Data and models both suggest that abrupt climate change during the last glaciation originated through changes in the Atlantic thermohaline circulation in response to small changes in the hydrological cycle. Atmospheric and oceanic responses to these changes were then transmitted globally through a number of feedbacks. The palaeoclimate data and the model results also indicate that the stability of the thermohaline circulation depends on the mean climate state.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Meltwater pulse 1A (mwp-1A) was a prominent feature of the last deglaciation, which led to a sea-level rise of ~20 meters in less than 500 years. Concurrent with mwp-1A was the onset of the ...Bolling-Allerød interstadial event (14,600 years before the present), which marked the termination of the last glacial period. Previous studies have been unable to reconcile a warm Northern Hemisphere with mwp-1A originating from the Laurentide or Fennoscandian ice sheets. With the use of a climate model of intermediate complexity, we demonstrate that with mwp-1A originating from the Antarctic Ice Sheet, consistent with recent sea-level fingerprinting inferences, the strength of North Atlantic Deep Water (NADW) formation increases, thereby warming the North Atlantic region and providing an explanation for the onset of the Bølling-Allerøod warm interval. The established mode of active NADW formation is then able to respond to subsequent freshwater forcing from the Laurentide and Fennoscandian ice sheets, setting the stage for the Younger Dryas cold period.
We present results from an intercomparison of 11 different climate models of intermediate complexity, in which the North Atlantic Ocean was subjected to slowly varying changes in freshwater input. ...All models show a characteristic hysteresis response of the thermohaline circulation to the freshwater forcing; which can be explained by Stommel's salt advection feedback. The width of the hysteresis curves varies between 0.2 and 0.5 Sv in the models. Major differences are found in the location of present‐day climate on the hysteresis diagram. In seven of the models, present‐day climate for standard parameter choices is found in the bi‐stable regime, in four models this climate is in the mono‐stable regime. The proximity of the present‐day climate to the Stommel bifurcation point, beyond which North Atlantic Deep Water formation cannot be sustained, varies from less than 0.1 Sv to over 0.5 Sv.
This study explores whether teacher reports of executive functions predict change in reading performance (i.e., reading development) for elementary‐aged students when controlling for direct ...assessments of executive functions and for teacher reports of students' literacy skills. Prior research has raised problems with the construct validity of teacher reports of executive functions but has yet to consider that these teacher reports might be related to teachers' perceptions of their students' literacy skills. The current study used Grades 3 through 5 data from nationally representative data (N = 6945) of students collected between 2014 and 2016 to examine the contributions of teacher reports of executive functions to change in reading performance over the course of a year with autoregressive structural equation models. Measures of executive functions tapped attentional focusing (in Grades 3 and 4), working memory (in Grade 3), and inhibitory control (in Grade 4). When controlling for a direct assessment of the same facet of executive function as the teacher report, the teacher report of executive function predicted next year's reading. However, controlling for a teacher report of students' literacy skills reduced the effect of teacher reports of executive functions to nearly 0 across models while not reducing the effect of direct assessments of executive functions. This finding held across student race and home language subgroups in multigroup analyses. Based on these findings, teacher reports of executive functions do not capture information about executive functions that predicts of reading development beyond the teachers' perceptions of their students' literacy skills. Further research is needed to determine how teacher reports of EF could be designed to capture EFs as applied to reading.
This study explores whether teacher reports of executive functions predict change in reading performance (i.e., reading development) for elementary‐aged students when controlling for direct assessments of executive functions and for teacher reports of students' literacy skills. Prior research has raised problems with the construct validity of teacher reports of executive functions but has yet to consider that these teacher reports might be related to teachers' perceptions of their students' literacy skills.
Black carbon should be included in the Kyoto framework, and treatment of short-lived gases like methane should change.
Expectations are high that the Kyoto Protocol, intended to reduce emissions of ...certain greenhouse gases (GHGs), will be extended after its first reporting period ends in 2012. The mechanisms available to meet Kyoto targets will likely also be extended. But our scientific understanding of the carbon and methane cycles and the radiative effects of black carbon were less developed in 1997, when the Kyoto Protocol was established, and in 2001, when the Marrakesh Accords solidified mechanism details. Before entering the second commitment period, international policy instruments should be both modified to correct internal inconsistencies and updated to reflect recent scientific advances. Such advances support changes to the protocol's treatment of short-lived gases, such as methane, and the inclusion of black carbon within the Kyoto framework.
A primary argument for the widespread production of media violence is that audiences want to watch violent content. This assumption is examined in this meta-analytic review of existing research on ...both selective exposure to and enjoyment of violence. The results show that violence has a significant effect on both selective exposure and enjoyment, but in different directions. Specifically, violence increases selective exposure but decreases enjoyment of content. Potential explanations for these effects and moderators that could influence the results (e.g., sex, aggressive personality traits, type of content) are considered, and the practical implications of these findings are discussed.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, PRFLJ, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Previous research has found that White audiences exhibit less preference for movies with minority casts than for movies with White casts. We conducted two experiments to explore why this race-based ...bias occurs and how to overcome it. In the first study, we examined potential mediators of the relationship between actors' race and intention to view movies with minority actors. Results indicated that perceptions of the intended audience fully mediated the relationship. The second study manipulated this perception via social media postings. Findings suggest the race bias can be eliminated for White audiences. Specifically, the drop in interest in seeing a movie with a Black cast was erased when Whites read positive comments about the film from other Whites.
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