Modeling the natural history of ductal carcinoma in situ based on population data

Background: The incidence of ductal carcinoma in situ (DCIS) has increased substantially since the introduction of mammography screening. Nevertheless, little is known about the natural history of preclinical DCIS in the absence of biopsy or complete excision. Methods: Two well-established population models evaluated six possible DCIS natural history submodels. The submodels assumed 30%, 50%, or 80% of breast lesions progress from undetectable DCIS to preclinical screen-detectable DCIS; each model additionally allowed or prohibited DCIS regression. Preclinical screen-detectable DCIS could also progress to clinical DCIS or invasive breast cancer (IBC). Applying US population screening dissemination patterns, the models projected age-specific DCIS and IBC incidence that were compared to Surveillance, Epidemiology, and End Results data. Models estimated mean sojourn time (MST) in the preclinical screen-detectable DCIS state, overdiagnosis, and the risk of progression from preclinical screen-detectable DCIS. Results: Without biopsy and surgical excision, the majority of DCIS (64-100%) in the preclinical screen-detectable state progressed to IBC in submodels assuming no DCIS regression (36-100% in submodels allowing for DCIS regression). DCIS overdiagnosis differed substantially between models and submodels, 3.1-65.8%. IBC overdiagnosis ranged 1.3-2.4%. Submodels assuming DCIS regression resulted in a higher DCIS overdiagnosis than submodels without DCIS regression. MST for progressive DCIS varied between 0.2 and 2.5 years. Conclusions: Our findings suggest that the majority of screen-detectable but unbiopsied preclinical DCIS lesions progress to IBC and that the MST is relatively short. Nevertheless, due to the heterogeneity of DCIS, more research is needed to understand the progression of DCIS by grades and molecular subtypes

Learning from multimedia and hypermedia

Computer-based multimedia and hypermedia resources (e.g., the world wide web) have become one of the primary sources of academic information for a majority of pupils and students. In line with this expansion in the field of education, the scientific study of learning from multimedia and hypermedia has become a very active field of research. In this chapter we provide a short overview with regard to research on learning with multimedia and hypermedia. In two review sections, we describe the educational benefits of multiple representations and of learner control, as these are the two defining characteristics of hypermedia. In a third review section we describe recent scientific trends in the field of multimedia/hypermedia learning. In all three review sections we will point to relevant European work on multimedia/hypermedia carried out within the last 5 years, and often carried out within the Kaleidoscope Network of Excellence. According to the interdisciplinary nature of the field this work might come not only from psychology, but also from technology or pedagogy. Comparing the different research activities on multimedia and hypermedia that have dominated the international scientific discourse in the last decade reveals some important differences. Most important, a gap seems to exist between researchers mainly interested in a “serious” educational use of multimedia/ hypermedia and researchers mainly interested in “serious” experimental research on learning with multimedia/hypermedia. Recent discussions about the pros and cons of “design-based research” or “use-inspired basic research” can be seen as a direct consequence of an increasing awareness of the tensions within these two different cultures of research on education

Systems analysis and controlled malaria infection in Europeans and Africans elucidate naturally acquired immunity

Controlled human infections provide opportunities to study the interaction between the immune system and malaria parasites, which is essential for vaccine development. Here, we compared immune signatures of malaria-naive Europeans and of Africans with lifelong malaria exposure using mass cytometry, RNA sequencing and data integration, before and 5 and 11 days after venous inoculation with Plasmodium falciparum sporozoites. We observed differences in immune cell populations, antigen-specific responses and gene expression profiles between Europeans and Africans and among Africans with differing degrees of immunity. Before inoculation, an activated/differentiated state of both innate and adaptive cells, including elevated CD161(+)CD4(+) T cells and interferon-gamma production, predicted Africans capable of controlling parasitemia. After inoculation, the rapidity of the transcriptional response and clusters of CD4(+) T cells, plasmacytoid dendritic cells and innate T cells were among the features distinguishing Africans capable of controlling parasitemia from susceptible individuals. These findings can guide the development of a vaccine effective in malaria-endemic regions.Malaria immunity can be acquired through natural infection, but the correlates of protection are still being determined. Yazdanbakhsh and colleagues combine experimental infection of volunteers with Plasmodium falciparum with systems analysis to throw light on the nature of protective immune responses.Radiolog

[Avian cytogenetics goes functional] Third report on chicken genes and chromosomes 2015

High-density gridded libraries of large-insert clones using bacterial artificial chromosome (BAC) and other vectors are essential tools for genetic and genomic research in chicken and other avian species... Taken together, these studies demonstrate that applications of large-insert clones and BAC libraries derived from birds are, and will continue to be, effective tools to aid high-throughput and state-of-the-art genomic efforts and the important biological insight that arises from them

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Erosion and sedimentation effects on soil : organic carbon redistribution in a complex landscape of western Ecuador

This study was conducted to evaluate how land-use changes affect the distribution of SOC within a complex tropical landscape through the processes of erosion and sedimentation. The objectives were: (i) to estimate the present SOC storage at a landscape scale using predictors such as slope, elevation, texture, land-use type and landscape position; (ii) to estimate soil redistribution under the present land-use conditions and under different land-use change scenarios using an erosion-sedimentation model; and (iii) to estimate the redistribution of SOC caused by erosion-sedimentation processes and its effect on landscape-scale SOC stocks. Implications for land-use policy options for the study area are also discussed. The study was conducted in the southern part of Manabi province in western Ecuador where 12 sites were selected in each of the three land-use systems (36 sites in total) to represent the two major physiographic soil units. The main agricultural land uses are coffee-agroforestry systems, pastures and upland rice fields. Using a general linear model with backward stepwise elimination, a model was developed for predicting SOC stocks (as the dependent variable) using the following regulatory factors (independent variables): elevation, slope, texture (as continuous variables), land-use type and soil-landform class (as categorical variables). Results showed that the significant variables that explained SOC stocks at the landscape scale were: elevation (P<0.01), texture (sand) (P<0.05), land-use type (LU1 = coffee-agroforestry; LU2 = pasture) (P<0.05), and soil-landform class (SL1 = lowland soils) (P<0.01), as reflected in the regression model. The highest SOC stocks (in the south-east corner of the area) were found in lowland soils on river valleys, river terraces and lower hills, whereas lower values were found in upland soils on higher landscape positions (north-west corner of the area). SOC stocks in the top 25 cm depth ranged from 30-87 Mg C ha-1 and the area-weighted mean was 63.6 Mg C ha-1. The SOC map illustrates that the actual SOC stocks were strongly related to topography and topography-related soil textural classes, suggesting that topography-driven water erosion and sedimentation processes play an important role in this landscape. Soil erosion losses and sedimentation gains showed stark contrasts among the four land-use change scenarios. SOC redistribution in the landscape, caused by land-use change effects on erosion and sedimentation, showed the highest impact in clay soil zones on depositional lower landscape positions and in lowland soils on river terraces, whereas the lowest impact was found in sand and loam soils on upper landscape positions