48 research outputs found
Discursive Shifts in Ethno-Nationalist Politics: On Politicization and Mediatization of the "Refugee Crisis" in Poland
This paper analyzes politicization and mediatization of immigration in Poland in the context of the recent European "refugee crisis." Although largely absent from Polish political discourse after 1989, anti-refugee and anti-immigration rhetoric has recently become extremely politically potent in Poland. The analysis shows that, soon taken over by other political groups, the new anti-immigration discourses have been enacted in Poland's public sphere by the right-wing populist party PiS (Law and Justice). Its discourse in offline and online media has drawn on discursive patterns including Islamophobia, Euro-scepticism, anti-internationalism, and historical patterns and templates of discrimination such as anti-Semitism
In-depth characterization of intratumoral heterogeneity in refractory B-cell non-Hodgkin lymphoma through the lens of a Research Autopsy Program
Intratumoral heterogeneity (ITH) provides the substrate for tumor evolution and treatment resistance, yet is remarkably understudied in lymphoma, due to the often limited amount of tissue that gets sampled during the routine diagnostic process, generally from a single nodal or extranodal site. Furthermore, the trajectory of how lymphoma, and especially non-Hodgkin lymphoma, spreads throughout the human body remains poorly understood. Here, we present a detailed characterization of ITH by applying whole-genome sequencing to spatially separated tumor samples harvested at the time of autopsy (n=24) and/or diagnosis (n=3) in three patients presenting with refractory B-cell non-Hodgkin lymphoma. Through deconvolution of bulk samples into clonal mixtures and inference of phylogenetic trees, we found evidence that polyclonal seeding underlies tumor dissemination in lymphoma. We identify mutation signatures associated with ancestral and descendant clones. In our series of patients with highly refractory lymphoma, the determinants of resistance were often harbored by founding clones, although there was also evidence of positive selection of driver mutations, likely under the influence of therapy. Lastly, we show that circulating tumor DNA is suitable for the detection of ancestral mutations but may miss a significant proportion of private mutations that can be detected in tissue. Our study clearly shows the existence of intricate patterns of regional and anatomical evolution that can only be disentangled through multi-regional tumor tissue profiling
Defining a common set of indicators to monitor road accidents in the European Union
BACKGROUND: currently road accidents are mostly monitored through mortality and injury rates. This paper reports the methodology and the results of a project set forth by the European Union (EU) and coordinated by the WHO aimed at identifying and evaluating a core set of indicators to monitor the causal chain of road accident health effects. The project is part of the ECOEHIS (Development of Environment and Health Indicators for European Union Countries). METHODS: a group of experts (WG), identified 14 indicators after a review of the information collected at the EU level, each of them representing a specific aspect of the DPSEEA (Driving, Pressure, State, Exposure, Effect, Action) model applied and adapted to the road accidents. Each indicator was scored according to a list of 16 criteria chosen by the WG. Those found to have a high score were analysed to determine if they were compatible with EU legislation and then tested in the feasibility study. RESULTS: 11 of the 14 indicators found to be relevant and compatible with the criteria of selection were proposed for the feasibility study. Mortality, injury, road accident rate, age of vehicle fleet, and distance travelled are the indicators recommended for immediate implementation. CONCLUSION: after overcoming the limitations that emerged (absence of a common definition of death by road accident and injury severity, underestimation of injuries, differences in information quality) this core set of indicators will allow Member States to carry out effective internal/external comparisons over time
WHO Air Quality Guidelines 2021-aiming for healthier air for all: a joint statement by medical, public health, scientific societies and patient representative organisations
[Extract] After years of intensive research and deliberations with experts across the globe, the World Health Organization (WHO) updated its 2005 Global Air Quality Guidelines (AQG) in September 2021 [1, 2]. The new air quality guidelines (WHO AQG) are ambitious and reflect the large impact that air pollution has on global health. They recommend aiming for annual mean concentrations of PM2.5 not exceeding 5 µg/m3 and NO2 not exceeding 10 µg/m3, and the peak season mean 8-hr ozone concentration not exceeding 60 µg/m3 [1]. For reference, the corresponding 2005 WHO guideline values for PM2.5 and NO2 were, respectively, 10 µg/m3 and 40 µg/m3 with no recommendation issued for long-term ozone concentrations [3]. While the guidelines are not legally binding, we hope they will influence air quality policy across the globe for many years to come
Integration of Expressed Sequence Tag Data Flanking Predicted RNA Secondary Structures Facilitates Novel Non-Coding RNA Discovery
Many computational methods have been used to predict novel non-coding RNAs (ncRNAs), but none, to our knowledge, have explicitly investigated the impact of integrating existing cDNA-based Expressed Sequence Tag (EST) data that flank structural RNA predictions. To determine whether flanking EST data can assist in microRNA (miRNA) prediction, we identified genomic sites encoding putative miRNAs by combining functional RNA predictions with flanking ESTs data in a model consistent with miRNAs undergoing cleavage during maturation. In both human and mouse genomes, we observed that the inclusion of flanking ESTs adjacent to and not overlapping predicted miRNAs significantly improved the performance of various methods of miRNA prediction, including direct high-throughput sequencing of small RNA libraries. We analyzed the expression of hundreds of miRNAs predicted to be expressed during myogenic differentiation using a customized microarray and identified several known and predicted myogenic miRNA hairpins. Our results indicate that integrating ESTs flanking structural RNA predictions improves the quality of cleaved miRNA predictions and suggest that this strategy can be used to predict other non-coding RNAs undergoing cleavage during maturation
Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival
Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR=0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR=1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features. Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds
Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease
BACKGROUND:
The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease.
METHODS:
In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina.
RESULTS:
At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91).
CONCLUSIONS:
Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)
Oxide behaviour in hot rolling
Oxide scale on the surface of metal plays a pivotal role in the thermomechanical processing and subsequent surface quality. The research reported here concerns the behaviour of perhaps the most complicated oxide scale, namely that on steels, undergoing hot rolling. By doing a closely-linked combination of laboratory testing and measurements, rolling tests, microstructural investigation and, crucially, detailed finite element analysis, a physically-based model for oxide scale behaviour has been developed. This model has been successfully applied to circumstances similar to those in which it was developed, namely hot rolling of steel. Importantly, it has also been applied to completely different circumstances, high temperature hydraulic descaling and room temperature mechanical descaling, with considerable success. This is clear affirmation of the integrity of the model. It is also an example of how a combination of techniques can allow materials to be characterised in circumstances where standard methods of measurement are not feasible or adequate on their own