How clumpy is my image?: Scoring in crowdsourced annotation tasks

The use of citizen science to obtain annotations from multiple annotators has been shown to be an effective method for annotating datasets in which computational methods alone are not feasible. The way in which the annotations are obtained is an important consideration which affects the quality of the resulting consensus annotation. In this paper, we examine three separate approaches to obtaining consensus scores for instances rather than merely binary classifications. To obtain a consensus score, annotators were asked to make annotations in one of three paradigms: classification, scoring and ranking. A web-based citizen science experiment is described which implements the three approaches as crowdsourced annotation tasks. The tasks are evaluated in relation to the accuracy and agreement among the participants using both simulated and real-world data from the experiment. The results show a clear difference in performance between the three tasks, with the ranking task obtaining the highest accuracy and agreement among the participants. We show how a simple evolutionary optimiser may be used to improve the performance by reweighting the importance of annotators

Targeting Antibiotics to Households for Trachoma Control

Repeated ocular infection with the bacterium Chlamydia trachomatis leads to the development of trachoma, a major cause of infectious blindness worldwide. Mass distribution of antibiotics, a component of the current trachoma control strategy, has had success in reducing infection in some areas, but results in a large number of uninfected people receiving antibiotics. We have previously shown that transmission of the bacteria between people in the same household is very efficient. Here, we investigated the effectiveness and cost-effectiveness of targeting antibiotics to households with active trachoma (inflammatory disease) compared to mass distribution, using data from four trachoma-endemic populations and a mathematical model of transmission. We found a high correspondence between households with active trachoma and infected households. In all populations the household targeted approach was predicted to be as effective as mass distribution, but it reduced the number of uninfected individuals receiving antibiotics, making the targeted strategy more cost-effective when antibiotics are not donated. Assuming antibiotics are donated, we predicted the targeted strategy to be more cost effective if it increases the proportion of infected individuals receiving treatment. Further work to address the feasibility and the cost variability in implementing the targeted approach in different settings is now required

Metachronic malignant transformation of small bowel and rectal endometriosis in the same patient

BACKGROUND: Malignant transformation of intestinal endometriosis is a rare event with an unknown rate of incidence. Metachronous progression of endometriosis to adenocarcinoma from two distant intestinal foci happening in the same patient has not been previously reported. CASE PRESENTATION: We describe a case of metachronic transformation of ileal and rectal endometriosis into an adenocarcinoma occurring in a 45-year-old female without macroscopic pelvic involvement of her endometriosis. First, a right colectomy was performed due to intestinal obstruction by an ileal mass. Pathological examination revealed an ileal endometrioid adenocarcinoma and contiguous microscopic endometriotic foci. Twenty months later, a rectal mass was discovered. An endoscopic biopsy revealed an adenocarcinoma. En bloc anterior rectum resection, hysterectomy and bilateral salpingectomy were performed. A second endometrioid adenocarcinoma arising from a focus of endometriosis within the wall of the rectum was diagnosed. CONCLUSION: Intestinal endometriosis should be considered a premalignant condition in premenopausal women

Human Cell Chips: Adapting DNA Microarray Spotting Technology to Cell-Based Imaging Assays

Here we describe human spotted cell chips, a technology for determining cellular state across arrays of cells subjected to chemical or genetic perturbation. Cells are grown and treated under standard tissue culture conditions before being fixed and printed onto replicate glass slides, effectively decoupling the experimental conditions from the assay technique. Each slide is then probed using immunofluorescence or other optical reporter and assayed by automated microscopy. We show potential applications of the cell chip by assaying HeLa and A549 samples for changes in target protein abundance (of the dsRNA-activated protein kinase PKR), subcellular localization (nuclear translocation of NFκB) and activation state (phosphorylation of STAT1 and of the p38 and JNK stress kinases) in response to treatment by several chemical effectors (anisomycin, TNFα, and interferon), and we demonstrate scalability by printing a chip with ∼4,700 discrete samples of HeLa cells. Coupling this technology to high-throughput methods for culturing and treating cell lines could enable researchers to examine the impact of exogenous effectors on the same population of experimentally treated cells across multiple reporter targets potentially representing a variety of molecular systems, thus producing a highly multiplexed dataset with minimized experimental variance and at reduced reagent cost compared to alternative techniques. The ability to prepare and store chips also allows researchers to follow up on observations gleaned from initial screens with maximal repeatability

Estrogen regulation of apoptosis: how can one hormone stimulate and inhibit?

The link between estrogen and the development and proliferation of breast cancer is well documented. Estrogen stimulates growth and inhibits apoptosis through estrogen receptor-mediated mechanisms in many cell types. Interestingly, there is strong evidence that estrogen induces apoptosis in breast cancer and other cell types. Forty years ago, before the development of tamoxifen, high-dose estrogen was used to induce tumor regression of hormone-dependent breast cancer in post-menopausal women. While the mechanisms by which estrogen induces apoptosis were not completely known, recent evidence from our laboratory and others demonstrates the involvement of the extrinsic (Fas/FasL) and the intrinsic (mitochondria) pathways in this process. We discuss the different apoptotic signaling pathways involved in E2 (17β-estradiol)-induced apoptosis, including the intrinsic and extrinsic apoptosis pathways, the NF-κB (nuclear factor-kappa-B)-mediated survival pathway as well as the PI3K (phosphoinositide 3-kinase)/Akt signaling pathway. Breast cancer cells can also be sensitized to estrogen-induced apoptosis through suppression of glutathione by BSO (L-buthionine sulfoximine). This finding has implications for the control of breast cancer with low-dose estrogen and other targeted therapeutic drugs

The Initial Mass Function in the Galactic Center

The Galactic Center contains the most massive young clusters in the Galaxy and serves as the closest example of a massive starburst region. Our recent results suggest that the Galactic Center environment produces massive clusters with relatively flat initial mass functions, as might be expected on theoretical grounds. I will discuss these recent results, along with evidence for star formation in the immediate vicinity of the super massive black hole at the Galactic Center. The results of this work might be useful in extrapolating to other galactic centers with similar conditions, as well as other starburst regions

Transglutaminase 6: a protein associated with central nervous system development and motor function.

Transglutaminases (TG) form a family of enzymes that catalyse various post-translational modifications of glutamine residues in proteins and peptides including intra- and intermolecular isopeptide bond formation, esterification and deamidation. We have characterized a novel member of the mammalian TG family, TG6, which is expressed in a human carcinoma cell line with neuronal characteristics and in mouse brain. Besides full-length protein, alternative splicing results in a short variant lacking the second β-barrel domain in man and a variant with truncated β-sandwich domain in mouse. Biochemical data show that TG6 is allosterically regulated by Ca(2+) and guanine nucleotides. Molecular modelling indicates that TG6 could have Ca(2+) and GDP-binding sites related to those of TG3 and TG2, respectively. Localization of mRNA and protein in the mouse identified abundant expression of TG6 in the central nervous system. Analysis of its temporal and spatial pattern of induction in mouse development indicates an association with neurogenesis. Neuronal expression of TG6 was confirmed by double-labelling of mouse forebrain cells with cell type-specific markers. Induction of differentiation in mouse Neuro 2a cells with NGF or dibutyryl cAMP is associated with an upregulation of TG6 expression. Familial ataxia has recently been linked to mutations in the TGM6 gene. Autoantibodies to TG6 were identified in immune-mediated ataxia in patients with gluten sensitivity. These findings suggest a critical role for TG6 in cortical and cerebellar neurons