Chromosomal conformations, topologically associated chromatin domains (TADs) assembling in nested fashion across hundreds of kilobases, and other "three-dimensional genome" (3DG) structures bypass the linear genome on a kilo- or megabase scale and play an important role in transcriptional regulation. Most of the genetic variants associated with risk for schizophrenia (SZ) are common and could be located in enhancers, repressors, and other regulatory elements that influence gene expression; however, the role of the brain's 3DG for SZ genetic risk architecture, including developmental and cell type–specific regulation, remains poorly understood. We monitored changes in 3DG after isogenic differentiation of human induced pluripotent stem cell–derived neural progenitor cells (NPCs) into neurons or astrocyte-like glial cells on a genome-wide scale using Hi-C. With this in vitro model of brain development, we mapped cell type–specific chromosomal conformations associated with SZ risk loci and defined a risk-associated expanded genome space. Neural differentiation was associated with genome-wide 3DG remodeling, including pruning and de novo formations of chromosomal loopings. The NPC-to-neuron transition was defined by the pruning of loops involving regulators of cell proliferation, morphogenesis, and neurogenesis, which is consistent with a departure from a precursor stage toward postmitotic neuronal identity. Loops lost during NPC-to-glia transition included many genes associated with neuron-specific functions, which is consistent with non-neuronal lineage commitment. However, neurons together with NPCs, as compared with glia, harbored a much larger number of chromosomal interactions anchored in common variant sequences associated with SZ risk. Because spatial 3DG proximity of genes is an indicator for potential coregulation, we tested whether the neural cell type–specific SZ-related "chromosomal connectome" showed evidence of coordinated transcriptional regulation and proteomic interaction of the participating genes. To this end, we generated lists of genes anchored in cell type–specific SZ risk-associated interactions. Thus, for the NPC-specific interactions, we counted 386 genes, including 146 within the risk loci and another 240 genes positioned elsewhere in the linear genome but connected via intrachromosomal contacts to risk locus sequences.
The drone makes a conspicuous racket as it lifts off on a mission to capture images of the reservoir below. The sight and sound of this strange device stirs interest among locals as they make their way to and from the town of Kasungu in central Malawi. It takes a matter of minutes for a small crowd to form. A few yards away, Patrick Kalonde is wading through grass and mud. Patrick, an intern at Unicef working on humanitarian uses of drones, is carrying a plastic container and a ladle and is looking for mosquito larvae. The contrast between high-tech drones and low-tech "bucket-and-spade" science, metres apart, could not be starker – yet both are equally important to the success of our new project to map where mosquitoes breed. Kasungu, a small town at the base of the picturesque Kasungu Mountain, is the centre of Africa's first humanitarian drone testing corridor. Set up by Unicef in 2017 with support from the Malawi government, the corridor is an 80km-wide area for flying and testing drones to help the local people. Keen to dispel the reputation that drones are only useful for destruction, the Unicef corridor promotes "drones for good".
Background: Overweight and obesity are an increasing phenomenon worldwide. Predicting future overweight or obesity early in the childhood reliably could enable a successful intervention by experts. While a lot of research has been done using explanatory modeling methods, capability of machine learning, and predictive modeling, in particular, remain mainly unexplored. In predictive modeling models are validated with previously unseen examples, giving a more accurate estimate of their performance and generalization ability in real-life scenarios. Objective: To find and review existing overweight or obesity research from the perspective of employing childhood data and predictive modeling methods. Methods: The initial phase included bibliographic searches using relevant search terms in PubMed, IEEE database and Google Scholar. The second phase consisted of iteratively searching references of potential studies and recent research that cite the potential studies. Results: Eight research articles and three review articles were identified as relevant for this review. Conclusions: Prediction models with high performance either have a relatively short time period to predict or/and are based on late childhood data. Logistic regression is currently the most often used method in forming the prediction models. In addition to child's own weight and height information, maternal weight status or body mass index was often used as predictors in the models.
A New York City based large volume private practice radiology group conducted a quality assurance review that included an 18 month software evaluation in the breast center comprised of nine (9) specialist radiologists using an FDA cleared artificial intelligence software by Koios Medical, Inc as a second opinion for analyzing and assessing lesions found during breast ultrasound examinations. Over the evaluation period, radiologists analyzed over 6,000 diagnostic breast ultrasound exams. Radiologists used Koios DS Breast decision support software (Koios Medical, Inc.) to assist in lesion classification and risk assessment. As part of the normal diagnostic workflow, radiologists would activate Koios DS and review the software findings with clinical details to formulate the best management. Analysis was then performed comparing the physicians' diagnostic performance to the 18-month period prior to the introduction of the AI enabled software.
The Normal Means problem plays a fundamental role in many areas of modern high-dimensional statistics, both in theory and practice. And the Empirical Bayes (EB) approach to solving this problem has been shown to be highly effective, again both in theory and practice. However, almost all EB treatments of the Normal Means problem assume that the observations are independent. In practice correlations are ubiquitous in real-world applications, and these correlations can grossly distort EB estimates. Here, exploiting theory from Schwartzman (2010), we develop new EB methods for solving the Normal Means problem that take account of unknown correlations among observations. We provide practical software implementations of these methods, and illustrate them in the context of large-scale multiple testing problems and False Discovery Rate (FDR) control. In realistic numerical experiments our methods compare favorably with other commonly-used multiple testing methods.