261 research outputs found
Changes in late adolescentsâ voting intentions during the election campaign: Disentangling the effects of political communication with parents, peers and media
This article investigates the effects of political discussions with parents, political discussions with peers and exposure to political news during an election campaign on the voting intentions and behaviour of first-time voters. Longitudinal data collected in the Czech Republic are employed in the main analysis (N=223). Results show that young people who frequently discuss politics with their peers are characterized by higher voting intentions and subsequent electoral participation. On the other hand, political discussions with parents and exposure to political news have no such effects. Furthermore, although it does not have an impact on voting intentions, more frequent political discussions with parents predict increased frequency of political discussions with peers. Overall, our results underscore the importance of peers in late adolescents' political socialization
Kinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancer.
Dysregulation of the PI3K-AKT-mTOR signaling network is a prominent feature of breast cancers. However, clinical responses to drugs targeting this pathway have been modest, possibly because of dynamic changes in cellular signaling that drive resistance and limit drug efficacy. Using a quantitative chemoproteomics approach, we mapped kinome dynamics in response to inhibitors of this pathway and identified signaling changes that correlate with drug sensitivity. Maintenance of AURKA after drug treatment was associated with resistance in breast cancer models. Incomplete inhibition of AURKA was a common source of therapy failure, and combinations of PI3K, AKT or mTOR inhibitors with the AURKA inhibitor MLN8237 were highly synergistic and durably suppressed mTOR signaling, resulting in apoptosis and tumor regression in vivo. This signaling map identifies survival factors whose presence limits the efficacy of targeted therapies and reveals new drug combinations that may unlock the full potential of PI3K-AKT-mTOR pathway inhibitors in breast cancer
An ecological analysis of colorectal cancer incidence and mortality: Differences by sexual orientation
<p>Abstract</p> <p>Background</p> <p>Some have suggested gays and lesbians may carry a greater burden of colorectal cancer. To date, individual sexual orientation data are not available in cancer surveillance registries. This prevents an assessment of differences in colorectal cancer incidence and mortality by sexual orientation, using individual-level data.</p> <p>Methods</p> <p>We use an ecological approach to examine differences in colorectal cancer incidence and mortality by county-level sexual orientation data. From the Surveillance, Epidemiology and End Results (SEER) Program we obtain population-based surveillance data on colorectal cancer incidence and mortality from 1996 to 2004. We use Census 2000 data on same-sex partnered households, a proxy of sexual orientation, to derive county-level sexual orientation data. Using multiple regression models, we examined the county-level association of sexual minority density with colorectal cancer incidence and mortality.</p> <p>Results</p> <p>After controlling for race and SES, we identify a significant positive association between greater density of sexual minority men and women and colorectal cancer incidence. With respect to colorectal cancer mortality, we identify a positive association with density of sexual minority men, but not women.</p> <p>Conclusions</p> <p>In the absence of surveillance data on sexual minority individuals, ecological analyses provide estimates of associations at the aggregate level, thereby providing crucial information for follow-up studies.</p
A copula model for marked point processes
The final publication (Diao, Liqun, Richard J. Cook, and Ker-Ai Lee. (2013) A copula model for marked point processes. Lifetime Data Analysis, 19(4): 463-489) is available at Springer via http://dx.doi.org/10.1007/s10985-013-9259-3Many chronic diseases feature recurring clinically important events. In addition, however, there
often exists a random variable which is realized upon the occurrence of each event reflecting the
severity of the event, a cost associated with it, or possibly a short term response indicating the
effect of a therapeutic intervention. We describe a novel model for a marked point process which
incorporates a dependence between continuous marks and the event process through the use of a
copula function. The copula formulation ensures that event times can be modeled by any intensity
function for point processes, and any multivariate model can be specified for the continuous
marks. The relative efficiency of joint versus separate analyses of the event times and the marks is
examined through simulation under random censoring. An application to data from a recent trial
in transfusion medicine is given for illustration.Natural Sciences and Engineering Research Council of Canada (RGPIN 155849); Canadian Institutes for Health Research (FRN 13887); Canada Research Chair (Tier 1) â CIHR funded (950-226626
Swimming with Predators and Pesticides: How Environmental Stressors Affect the Thermal Physiology of Tadpoles
To forecast biological responses to changing environments, we need to understand how a speciesâs physiology varies through space and time and assess how changes in physiological function due to environmental changes may interact with phenotypic changes caused by other types of environmental variation. Amphibian larvae are well known for expressing environmentally induced phenotypes, but relatively little is known about how these responses might interact with changing temperatures and their thermal physiology. To address this question, we studied the thermal physiology of grey treefrog tadpoles (Hyla versicolor) by determining whether exposures to predator cues and an herbicide (Roundup) can alter their critical maximum temperature (CTmax) and their swimming speed across a range of temperatures, which provides estimates of optimal temperature (Topt) for swimming speed and the shape of the thermal performance curve (TPC). We discovered that predator cues induced a 0.4uC higher CTmax value, whereas the herbicide had no effect. Tadpoles exposed to predator cues or the herbicide swam faster than control tadpoles and the increase in burst speed was higher near Topt. In regard to the shape of the TPC, exposure to predator cues increased Topt by 1.5uC, while exposure to the herbicide marginally lowered Topt by 0.4uC. Combining predator cues and the herbicide produced an intermediate Topt that was 0.5uC higher than the control. To our knowledge this is the first study to demonstrate a predator altering the thermal physiology of amphibian larvae (prey) by increasing CTmax, increasing the optimum temperature, and producing changes in the thermal performance curves. Furthermore, these plastic responses of CTmax and TPC to different inducing environments should be considered when forecasting biological responses to global warming.Peer reviewe
Are all âresearch fieldsâ equal? Rethinking practice for the use of data from crowd-sourcing market places
New technologies like large-scale social media sides (e.g., Facebook and Twitter) and crowdsourcing services (e.g., Amazon Mechanical Turk, Crowdflower, Clickworker) impact social science research and provide many new and interesting avenues for research. The use of these new technologies for research has not been without challenges and a recently published psychological study on Facebook led to a widespread discussion on the ethics of conducting large-scale experiments online. Surprisingly little has been said about the ethics of conducting research using commercial crowdsourcing market places. In this paper, I want to focus on the question of which ethical questions are raised by data collection with crowdsourcing tools. I briefly draw on implications of internet research more generally and then focus on the specific challenges that research with crowdsourcing tools faces. I identify fair-pay and related issues of respect for autonomy as well as problems with power dynamics between researcher and participant, which has implications for âwithdrawal-withoutprejudiceâ, as the major ethical challenges with crowdsourced data. Further, I will to draw attention on how we can develop a âbest practiceâ for researchers using crowdsourcing tools
Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers
Epithelial cell adhesion molecule (Ep-CAM; CD326) is used as a target by many immunotherapeutic approaches, but little data are available about Ep-CAM expression in major human malignancies with respect to level, frequency, tumour stage, grade, histologic tumour type and impact on survival. We analysed by immunohistochemical staining tissue microarrays with 4046 primary human carcinoma samples from colon, stomach, prostate and lung cancers for both frequency and intensity of Ep-CAM expression under highly standardised conditions. A total of 3360 samples were analysable. High-level Ep-CAM expression was observed in 97.7% (n=1186) of colon, 90.7% of gastric (n=473), and 87.2% of prostate cancers (n=414), and in 63.9% of lung cancers (n=1287). No detectable Ep-CAM staining was found with only 0.4% of colon, 2.5% of gastric, 1.9% of prostate cancers, and 13.5% of lung cancers. The only significant correlation of Ep-CAM expression with tumour grading was observed in colon cancer where high-level Ep-CAM expression on grade 3 tumours was down to 92.1% (P<0.0001). Adenosquamous and squamous carcinomas of the lung had a lower percentage of high-level Ep-CAM expression compared to adenocarcinomas with 35.4 and 53.6%, respectively, and with 45.5 and 17.3% of tumours being Ep-CAM negative. With the exception of moderately differentiated colon carcinoma, where patients not expressing Ep-CAM on their tumours showed an inferior survival (P=0.0014), correlation of Ep-CAM expression with survival did not reach statistical significance for any of the other cancer indications and subgroups. In conclusion, the data strongly support the notion that Ep-CAM is a prime target for immunotherapies in major human malignancies. This is because the most common human cancers show (i) a low frequency of Ep-CAM-negative tumours, (ii) a high frequency of Ep-CAM expression on cells of a given tumour, and (iii) for most cancers, an insignificant influence of tumour staging, grading and histology on Ep-CAM expression
Primary brain calcification: an international study reporting novel variants and associated phenotypes.
Primary familial brain calcification (PFBC) is a rare cerebral microvascular calcifying disorder with a wide spectrum of motor, cognitive, and neuropsychiatric symptoms. It is typically inherited as an autosomal-dominant trait with four causative genes identified so far: SLC20A2, PDGFRB, PDGFB, and XPR1. Our study aimed at screening the coding regions of these genes in a series of 177 unrelated probands that fulfilled the diagnostic criteria for primary brain calcification regardless of their family history. Sequence variants were classified as pathogenic, likely pathogenic, or of uncertain significance (VUS), based on the ACMG-AMP recommendations. We identified 45 probands (25.4%) carrying either pathogenic or likely pathogenic variants (nâ=â34, 19.2%) or VUS (nâ=â11, 6.2%). SLC20A2 provided the highest contribution (16.9%), followed by XPR1 and PDGFB (3.4% each), and PDGFRB (1.7%). A total of 81.5% of carriers were symptomatic and the most recurrent symptoms were parkinsonism, cognitive impairment, and psychiatric disturbances (52.3%, 40.9%, and 38.6% of symptomatic individuals, respectively), with a wide range of age at onset (from childhood to 81 years). While the pathogenic and likely pathogenic variants identified in this study can be used for genetic counseling, the VUS will require additional evidence, such as recurrence in unrelated patients, in order to be classified as pathogenic
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