60 research outputs found

    A Test-Retest Transition Matrix: A Modification of McNemar’s Test

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    McNemar introduced what is known today as a test for symmetry in a two by two contingency tables. The logic of the test is based on a sample of matched pairs with a dichotomous response. In our example, the sample consists of the scores before and after an education program and the responses before and after the program. Each pair of scores is from only one person. The pretest divides the group of responders according to their answers to a dichotomous question. The posttest divides the two groups into two groups of like labels. The result is a two by two table. We construct a test of homogeneity, where the proportion of initially partitioned subjects will be equally distributed over the same partition after the program is completed, conditioned on the initial distribution

    On Treating A Survey Of Convenience Sample As A Simple Random Sample

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    Threat of bias has kept many from using data gathered in less than optimal conditions. We maintain that when convenience sampling represents race and gender at nearly correct proportions and can be beneficial, as these two variables are quite often used as stratification variables. We compared a convenience sample with a proven sample. Race and Sex were nearly proportional as was found in the proven sample. We conclude that the convenience sample can be used as though it is simple random

    Dynamic Chromatin Organization during Foregut Development Mediated by the Organ Selector Gene PHA-4/FoxA

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    Central regulators of cell fate, or selector genes, establish the identity of cells by direct regulation of large cohorts of genes. In Caenorhabditis elegans, foregut (or pharynx) identity relies on the FoxA transcription factor PHA-4, which activates different sets of target genes at various times and in diverse cellular environments. An outstanding question is how PHA-4 distinguishes between target genes for appropriate transcriptional control. We have used the Nuclear Spot Assay and GFP reporters to examine PHA-4 interactions with target promoters in living embryos and with single cell resolution. While PHA-4 was found throughout the digestive tract, binding and activation of pharyngeally expressed promoters was restricted to a subset of pharyngeal cells and excluded from the intestine. An RNAi screen of candidate nuclear factors identified emerin (emr-1) as a negative regulator of PHA-4 binding within the pharynx, but emr-1 did not modulate PHA-4 binding in the intestine. Upon promoter association, PHA-4 induced large-scale chromatin de-compaction, which, we hypothesize, may facilitate promoter access and productive transcription. Our results reveal two tiers of PHA-4 regulation. PHA-4 binding is prohibited in intestinal cells, preventing target gene expression in that organ. PHA-4 binding within the pharynx is limited by the nuclear lamina component EMR-1/emerin. The data suggest that association of PHA-4 with its targets is a regulated step that contributes to promoter selectivity during organ formation. We speculate that global re-organization of chromatin architecture upon PHA-4 binding promotes competence of pharyngeal gene transcription and, by extension, foregut development

    A Cross-Species Analysis of MicroRNAs in the Developing Avian Face

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    Higher vertebrates use similar genetic tools to derive very different facial features. This diversity is believed to occur through temporal, spatial and species-specific changes in gene expression within cranial neural crest (NC) cells. These contribute to the facial skeleton and contain species-specific information that drives morphological variation. A few signaling molecules and transcription factors are known to play important roles in these processes, but little is known regarding the role of micro-RNAs (miRNAs). We have identified and compared all miRNAs expressed in cranial NC cells from three avian species (chicken, duck, and quail) before and after species-specific facial distinctions occur. We identified 170 differentially expressed miRNAs. These include thirty-five novel chicken orthologs of previously described miRNAs, and six avian-specific miRNAs. Five of these avian-specific miRNAs are conserved over 120 million years of avian evolution, from ratites to galliforms, and their predicted target mRNAs include many components of Wnt signaling. Previous work indicates that mRNA gene expression in NC cells is relatively static during stages when the beak acquires species-specific morphologies. However, miRNA expression is remarkably dynamic within this timeframe, suggesting that the timing of specific developmental transitions is altered in birds with different beak shapes. We evaluated one miRNA:mRNA target pair and found that the cell cycle regulator p27KIP1 is a likely target of miR-222 in frontonasal NC cells, and that the timing of this interaction correlates with the onset of phenotypic variation. Our comparative genomic approach is the first comprehensive analysis of miRNAs in the developing facial primordial, and in species-specific facial development

    Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

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    Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower postoperative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we provide a detailed overview of possible underlying factors that link COPD and lung cancer, and current therapeutic advances from both human and preclinical animal models that can effectively mitigate this unholy relationship

    Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

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    Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

    Development and reproductive performance of Hereford heifers of different frame sizes up to mating at 14-15 months of age

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    ABSTRACT Body development and reproductive performance of a hundred forty-two 14 to 15-month-old heifers, classified at weaning according to frame size as small, medium, and large, were evaluated. The parameters evaluated were: body weight, hip height, body condition score, weight gain, ovarian activity, and pregnancy rate. At weaning, body weight and hip height were significantly different among frame scores, (small – 133.0 kg, 92.2 cm; medium – 158.5 kg, 96.6 cm; and large – 185.2 kg; 100.2 cm). After weaning, heifers grazed together on natural pastures during the autumn and on ryegrass (Lolium multiflorum La.) during the winter and spring. Frame score differences remained until the beginning of the breeding season (BS), starting on average at 14 months of age. Weight gain between weaning and the beginning of BS was not different among frame scores (0.740 kg/day, on average). Body weights at the beginning of the BS were significantly different, of 255.7 kg (53.3% of the mature weight) for small heifers, 285.0 kg (59.4%) for medium heifers, and 307.6 kg (64.1%) for large heifers. Ovarian activity at the beginning of the BS was not different among the three groups. The average weight gain values during the BS of 0.492, 0.472, and 0.421 kg/day for small, medium, and large heifers, respectively, were significantly different. Pregnancy rates were not different among groups (small, 71.4%; medium, 76.4%; and large, 76.5%). Frame score did not influence the reproductive performance of heifers, but the small and medium heifers conceived 29 and 20 days earlier, respectively, than the large heifers

    E Pluribus Unum? Varieties and Commonalities of Capitalism

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