2,352 research outputs found

    Changes in prostate‐specific antigen at the time of prostate cancer diagnosis after Medicaid expansion in young men

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155914/1/cncr32930_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155914/2/cncr32930.pd

    Testing for independence in J × K contingency tables with complex sample survey data

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    Summary: The test of independence of row and column variables in a (J × K) contingency table is a widely used statistical test in many areas of application. For complex survey samples, use of the standard Pearson chi-squared test is inappropriate due to correlation among units within the same cluster

    Ferret and Pig Models of Cystic Fibrosis: Prospects and Promise for Gene Therapy

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    Large animal models of genetic diseases are rapidly becoming integral to biomedical research as technologies to manipulate the mammalian genome improve. The creation of cystic fibrosis (CF) ferrets and pigs is an example of such progress in animal modeling, with the disease phenotypes in the ferret and pig models more reflective of human CF disease than mouse models. The ferret and pig CF models also provide unique opportunities to develop and assess the effectiveness of gene and cell therapies to treat affected organs. In this review, we examine the organ disease phenotypes in these new CF models and the opportunities to test gene therapies at various stages of disease progression in affected organs. We then discuss the progress in developing recombinant replication-defective adenoviral, adeno-associated viral, and lentiviral vectors to target genes to the lung and pancreas in ferrets and pigs, the two most affected organs in CF. Through this review, we hope to convey the potential of these new animal models for developing CF gene and cell therapies

    Comparison of next generation sequencing technologies for transcriptome characterization

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    <p>Abstract</p> <p>Background</p> <p>We have developed a simulation approach to help determine the optimal mixture of sequencing methods for most complete and cost effective transcriptome sequencing. We compared simulation results for traditional capillary sequencing with "Next Generation" (NG) ultra high-throughput technologies. The simulation model was parameterized using mappings of 130,000 cDNA sequence reads to the <it>Arabidopsis </it>genome (NCBI Accession SRA008180.19). We also generated 454-GS20 sequences and <it>de novo </it>assemblies for the basal eudicot California poppy (<it>Eschscholzia californica</it>) and the magnoliid avocado (<it>Persea americana</it>) using a variety of methods for cDNA synthesis.</p> <p>Results</p> <p>The <it>Arabidopsis </it>reads tagged more than 15,000 genes, including new splice variants and extended UTR regions. Of the total 134,791 reads (13.8 MB), 119,518 (88.7%) mapped exactly to known exons, while 1,117 (0.8%) mapped to introns, 11,524 (8.6%) spanned annotated intron/exon boundaries, and 3,066 (2.3%) extended beyond the end of annotated UTRs. Sequence-based inference of relative gene expression levels correlated significantly with microarray data. As expected, NG sequencing of normalized libraries tagged more genes than non-normalized libraries, although non-normalized libraries yielded more full-length cDNA sequences. The <it>Arabidopsis </it>data were used to simulate additional rounds of NG and traditional EST sequencing, and various combinations of each. Our simulations suggest a combination of FLX and Solexa sequencing for optimal transcriptome coverage at modest cost. We have also developed ESTcalc <url>http://fgp.huck.psu.edu/NG_Sims/ngsim.pl</url>, an online webtool, which allows users to explore the results of this study by specifying individualized costs and sequencing characteristics.</p> <p>Conclusion</p> <p>NG sequencing technologies are a highly flexible set of platforms that can be scaled to suit different project goals. In terms of sequence coverage alone, the NG sequencing is a dramatic advance over capillary-based sequencing, but NG sequencing also presents significant challenges in assembly and sequence accuracy due to short read lengths, method-specific sequencing errors, and the absence of physical clones. These problems may be overcome by hybrid sequencing strategies using a mixture of sequencing methodologies, by new assemblers, and by sequencing more deeply. Sequencing and microarray outcomes from multiple experiments suggest that our simulator will be useful for guiding NG transcriptome sequencing projects in a wide range of organisms.</p

    MRI-targeted or standard biopsy for prostate-cancer diagnosis

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    Background Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. Methods In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. Results A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; P&lt;0.001). Conclusions The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027 .)

    Phytoplankton functional types from Space.

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    The concept of phytoplankton functional types has emerged as a useful approach to classifying phytoplankton. It finds many applications in addressing some serious contemporary issues facing science and society. Its use is not without challenges, however. As noted earlier, there is no universally-accepted set of functional types, and the types used have to be carefully selected to suit the particular problem being addressed. It is important that the sum total of all functional types matches all phytoplankton under consideration. For example, if in a biogeochemical study, we classify phytoplankton as silicifiers, calcifiers, DMS-producers and nitrogen fix- ers, then there is danger that the study may neglect phytoplankton that do not contribute in any significant way to those functions, but may nevertheless be a significant contributor to, say primary production. Such considerations often lead to the adoption of a category of “other phytoplankton” in models, with no clear defining traits assigned them, but that are nevertheless necessary to close budgets on phytoplankton processes. Since this group is a collection of all phytoplankton that defy classification according to a set of traits, it is difficult to model their physi- ological processes. Our understanding of the diverse functions of phytoplankton is still growing, and as we recognize more functions, there will be a need to balance the desire to incorporate the increasing number of functional types in models against observational challenges of identifying and mapping them adequately. Modelling approaches to dealing with increasing functional diversity have been proposed, for example, using the complex adaptive systems theory and system of infinite diversity, as in the work of Bruggemann and Kooijman (2007). But it is unlikely that remote-sensing approaches might be able to deal with anything but a few prominent functional types. As long as these challenges are explicitly addressed, the functional- type concept should continue to fill a real need to capture, in an economic fashion, the diversity in phytoplankton, and remote sensing should continue to be a useful tool to map them. Remote sensing of phytoplankton functional types is an emerging field, whose potential is not fully realised, nor its limitations clearly established. In this report, we provide an overview of progress to date, examine the advantages and limitations of various methods, and outline suggestions for further development. The overview provided in this chapter is intended to set the stage for detailed considerations of remote-sensing applications in later chapters. In the next chapter, we examine various in situ methods that exist for observing phytoplankton functional types, and how they relate to remote-sensing techniques. In the subsequent chapters, we review the theoretical and empirical bases for the existing and emerging remote-sensing approaches; assess knowledge about the limitations, assumptions, and likely accuracy or predictive skill of the approaches; provide some preliminary comparative analyses; and look towards future prospects with respect to algorithm development, validation studies, and new satellite mis- sions

    Introductory programming: a systematic literature review

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    As computing becomes a mainstream discipline embedded in the school curriculum and acts as an enabler for an increasing range of academic disciplines in higher education, the literature on introductory programming is growing. Although there have been several reviews that focus on specific aspects of introductory programming, there has been no broad overview of the literature exploring recent trends across the breadth of introductory programming. This paper is the report of an ITiCSE working group that conducted a systematic review in order to gain an overview of the introductory programming literature. Partitioning the literature into papers addressing the student, teaching, the curriculum, and assessment, we explore trends, highlight advances in knowledge over the past 15 years, and indicate possible directions for future research
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