403 research outputs found

    Integrity and Integration: An Exploration of the Personal, Professional, and Pedagogical in the Professoriate

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    This paper seeks to explore the connections between the concepts of integrity and integration within the professoriate in Christian higher education. Specifically, it examines commonalities and intersections in the definitions of terms, the gaps between rhetoric and reality, and the reasons for those gaps. Implications for a professor’s inner life, scholarship, and teaching are also discussed, and suggestions for closing the gaps are offered

    Comparison of Estimations Versus Measured Oxygen Consumption at Rest in Patients With Heart Failure and Reduced Ejection Fraction Who Underwent Right-Sided Heart Catheterization

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    Cardiac output during right-sided heart catheterization is an important variable for patient selection of advanced therapies (cardiac transplantation and left ventricular assist device implantation). The Fick method to determine cardiac output is commonly used and typically uses estimated oxygen consumption (VO2) from 1 of 3 published empirical formulas. However, these estimation equations have not been validated in patients with heart failure and reduced ejection fraction (HFrEF). The objectives of the present study were to determine the accuracy of 3 equations for estimating VO2 compared with direct measurement of VO2 and determine the extent clinically significant error occurred in calculating cardiac output of patients with HFrEF. Breath-by-breath measurements of VO2 from 44 patients who underwent cardiac catheterization (66% men; age, 65±11 years, left ventricular ejection fraction, 22±6%) were compared with the derived estimations of LaFarge and Miettinen, Dehmer et al, and Bergstra et al. Single-sample ttests found only the mean difference between the estimation of LaFarge and Miettinen and the measured VO2 to be nonsignificant (-10.3 ml/min±6.2 SE, p=0.053). Bland-Altman plots demonstrated unacceptably large limits of agreement for all equations. The rate of=25% error in the equations by LaFarge and Miettinen, Dehmer et al, and Bergstra et al occurred in 11%, 23%, and 45% of patients, respectively. Misclassification of cardiac index derived from each equation for 2 clinically important classifications: cardiogenic shock–21%, 23%, and 32% and hypoperfusion–16%, 16%, and 25%; respectively. In conclusion, these findings do not support the use of these empiric formulas to estimate the VO2 at rest in patients with HFrEF who underwent right-sided heart catheterization

    Physiological risk profiles and allostatic load: Using latent profile analysis to examine socioeconomic differences in physiological patterns of risk

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    Purpose. The current study sought to expand implications of physiological weathering through the application of latent profile analysis to stress biomarkers to address limitations of traditional allostatic load calculations. Methods. Latent profile analysis was applied biomarkers used in traditional allostatic load metrics to identify physiological risk profiles in the 2007-20010 National Health and Nutritional and Examination Survey. Multinomial logistic regression was used to determine the probability of risk profiles by race/ethnicity, age, gender, and poverty income ratio (PIR). Mean allostatic load score was assessed across each risk profile. Results. Latent profile analysis identified four distinct profiles labeled low risk, inflammatory risk, cardiovascular risk, and hypertension risk. Race, age, and gender significantly increased odds of exhibiting a risk profile. Compared to Whites, Hispanics had significant higher odds of inflammatory (OR=1.43, 95% CI [1.06-1.92]) and cardiovascular risk profiles (OR=1.63, 95% CI [1.09-2.43]) while Blacks had higher odds of inflammatory (OR=1.76 95% CI [1.25-2.47]), cardiovascular (OR=2.12, 95% CI, [1.39-3.27]) and hypertension risk profiles (OR= 1.78, 95% CI [1.21-2.59]). Females held significant greater odds of all risk categories except hypertension in which they held the lowest odds (OR= .19, 95% CI [.14-.25]). Mean allostatic load scores were highest in the inflammatory (M=3.99, SD=1.66) and cardiovascular risk profiles (M=4.4, SD=1.84). Conclusions. Employing latent profile analysis may expand traditional allostatic load methodology by identifying physiological risk patterns among those who experience allostatic load early in life. This may be useful for examining how cultural specific interventions may reduce cardiovascular risk among those exhibiting physiological risk profiles

    Organizational Agility through Project Portfolio Management

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    In dynamic environments, organizational agility is essential for survival; organizations must be able to adapt to change in order to succeed. In project-based organizations, a dynamic project portfolio management (PPM) capability can enhance organizational agility. PPM is an important organizational capability that enables organizations to manage and balance the portfolio holistically, to align projects with strategy, and to ensure adequate resourcing for projects in order to maximize the benefits from project investments. A dynamic PPM capability enables organizations to be agile and flexible by facilitating adjustments to the project portfolio and reallocating resources in response to the changes in the environment. In order for the PPM capability to remain relevant, it must evolve to reflect changes in the environment. Examples of aspects of PPM that enhance organizational agility are outlined in this paper to provide guidance for practitioners

    Unexpected mitochondrial genome diversity revealed by targeted single-cell genomics of heterotrophic flagellated protists

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    This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this recordData availability: Complete mtDNA sequences assembled from this study are available at GenBank under the accession numbers MK188935 to MK188947, MN082144 and MN082145. Sequencing data are available under NCBI BioProject PRJNA379597. Reads have been deposited at NCBI Sequence Read Archive with accession number SRP102236. Partial mtDNA contigs and other important contigs mentioned in the text are available from Figshare at https://doi.org/10.6084/m9.figshare.7314728. Nuclear SAG assemblies are available from Figshare at https://doi.org/10.6084/m9.figshare.7352966. A protocol is available from protocols.io at: https://doi.org/10.17504/protocols.io.ywpfxdn.Code availability: The bioinformatic workflow is available at https://doi.org/10.5281/zenodo.192677; additional statistical analysis code is available at https://doi.org/10.6084/m9.figshare.9884309.Most eukaryotic microbial diversity is uncultivated, under-studied and lacks nuclear genome data. Mitochondrial genome sampling is more comprehensive, but many phylogenetically important groups remain unsampled. Here, using a single-cell sorting approach combining tubulin-specific labelling with photopigment exclusion, we sorted flagellated heterotrophic unicellular eukaryotes from Pacific Ocean samples. We recovered 206 single amplified genomes, predominantly from underrepresented branches on the tree of life. Seventy single amplified genomes contained unique mitochondrial contigs, including 21 complete or near-complete mitochondrial genomes from formerly under-sampled phylogenetic branches, including telonemids, katablepharids, cercozoans and marine stramenopiles, effectively doubling the number of available samples of heterotrophic flagellate mitochondrial genomes. Collectively, these data identify a dynamic history of mitochondrial genome evolution including intron gain and loss, extensive patterns of genetic code variation and complex patterns of gene loss. Surprisingly, we found that stramenopile mitochondrial content is highly plastic, resembling patterns of variation previously observed only in plants.Gordon and Betty Moore FoundationLeverhulme TrustDavid and Lucile Packard FoundationRoyal SocietyEuropean Molecular Biology OrganizationCONICYT FONDECYTGenome Canad

    First report of mitochondrial COI in foraminifera and implications for DNA barcoding

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    Foraminifera are a species-rich phylum of rhizarian protists that are highly abundant in many marine environments and play a major role in global carbon cycling. Species recognition in Foraminifera is mainly based on morphological characters and nuclear 18S ribosomal RNA barcoding. The 18S rRNA contains variable sequence regions that allow for the identification of most foraminiferal species. Still, some species show limited variability, while others contain high levels of intragenomic polymorphisms, thereby complicating species identification. The use of additional, easily obtainable molecular markers other than 18S rRNA will enable more detailed investigation of evolutionary history, population genetics and speciation in Foraminifera. Here we present the first mitochondrial cytochrome c oxidase subunit 1 (COI) gene sequences ("barcodes") of Foraminifera. We applied shotgun sequencing to single foraminiferal specimens, assembled COI, and developed primers that allow amplification of COI in a wide range of foraminiferal species. We obtained COI sequences of 49 specimens from 17 species from the orders Rotaliida and Miliolida. Phylogenetic analysis showed that the COI tree is largely congruent with previously published 18S rRNA phylogenies. Furthermore, species delimitation with ASAP and ABGD algorithms showed that foraminiferal species can be identified based on COI barcodes.Microbial BiotechnologyNaturali

    CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity.

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    Hexanucleotide-repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). The nucleotide-repeat expansions are translated into dipeptide-repeat (DPR) proteins, which are aggregation prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 DPR toxicity in human cells. We validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. We uncovered potent modifiers of DPR toxicity whose gene products function in nucleocytoplasmic transport, the endoplasmic reticulum (ER), proteasome, RNA-processing pathways, and chromatin modification. One modifier, TMX2, modulated the ER-stress signature elicited by C9ORF72 DPRs in neurons and improved survival of human induced motor neurons from patients with C9ORF72 ALS. Together, our results demonstrate the promise of CRISPR-Cas9 screens in defining mechanisms of neurodegenerative diseases
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