404 research outputs found
Scientific Bounty Among Meteorites Recovered from the Dominion Range, Transantarctic Mountains
The US Antarctic Meteorite Pro-gram has visited the Dominion Range in the Transantarctic Mountains during several different sea-sons, including 1985, 2003, 2008, 2010, 2014 and 2018. Total recovered meteorites from this region is close to 3000. The 1985 (11 samples), 2003 (141 samples), 2008 (521 samples), 2010 (901 samples), 2014 (562 samples) seasons have been fully classified, and 2018 (865 samples) are in the process of being classified and characterized. Given that close to 2200 samples have been classified so far, with more expected in 2020, now is a good time to summarize the state of the collection. Here we describe the significant samples documented from this area, as well as a large meteorite shower that dominates the statistics of the region
Potential of Low Dose Leuco-Methylthioninium Bis(Hydromethanesulphonate) (LMTM) Monotherapy for Treatment of Mild Alzheimer’s Disease : Cohort Analysis as Modified Primary Outcome in a Phase III Clinical Trial
The supplementary material is available in the electronic version of this article: http://dx.doi.org/10.3233/JAD-170560. The study was sponsored by TauRx Therapeutics (Singapore). We thank Lon Schneider and Howard Feldman for their contribution to the Scientific Advisory Board. We gratefully acknowledge study investigators and the generosity of study participants. Authors’ disclosures available online (http://j-alz.com/manuscript disclosures/17-0560r3).Peer reviewedPublisher PD
A Controlled Investigation of Optimal Internal Medicine Ward Team Structure at a Teaching Hospital
BACKGROUND: The optimal structure of an internal medicine ward team at a teaching hospital is unknown. We hypothesized that increasing the ratio of attendings to housestaff would result in an enhanced perceived educational experience for residents. METHODS: Harbor-UCLA Medical Center (HUMC) is a tertiary care, public hospital in Los Angeles County. Standard ward teams at HUMC, with a housestaff∶attending ratio of 5:1, were split by adding one attending and then dividing the teams into two experimental teams containing ratios of 3:1 and 2:1. Web-based Likert satisfaction surveys were completed by housestaff and attending physicians on the experimental and control teams at the end of their rotations, and objective healthcare outcomes (e.g., length of stay, hospital readmission, mortality) were compared. RESULTS: Nine hundred and ninety patients were admitted to the standard control teams and 184 were admitted to the experimental teams (81 to the one-intern team and 103 to the two-intern team). Patients admitted to the experimental and control teams had similar age and disease severity. Residents and attending physicians consistently indicated that the quality of the educational experience, time spent teaching, time devoted to patient care, and quality of life were superior on the experimental teams. Objective healthcare outcomes did not differ between experimental and control teams. CONCLUSIONS: Altering internal medicine ward team structure to reduce the ratio of housestaff to attending physicians improved the perceived educational experience without altering objective healthcare outcomes
PenQuest Volume 1, Number 2
Table of Contents for this Volume:
Untitled by Julie Ambrose
Night by Judith Gallo
Untitled by Judy Gozdur
the shamans by Charles Riddles
Untitled by Jerry Connell
Untitled by Laura Woods
Untitled by LEMA
Wicked Bird by Laura Jo Last
Untitled by Rick Dentos
Untitled by Jeni Moody
Untitled by Bettie W. Kwibs
Untitled by Joann Stagg
The Protector Stood by Laura Jo Last
Visions of Salome by Charles Riddles
Untitled by Thomas Tutten
Kennesaw Line by Don Ova-Dunaway
Stone Blood by Mary Ellen C. Wofford
Untitled by Roger Whitt Jr.
Untitled by C. Wingate
Untitled by Doug Dorey
Untitled by Karen Blumberg
Untitled by Beverly Oviatt
Untitled by Virginia Shrader
The Crapulous Credo of Charles C. by Charles Riddles
the brave and the true by David Reed
Untitled by Charles Gutierrez
Canoe Creek by Patricia Kraft
Untitled by Linda Bobinger
The Man in the Iron Lung by Patricia Kraft
Untitled by Roger Whitt, Jr.
Childish Things by Kathleen Gay
Untitled by Joseph Avanzini
The Lover by Mary S. Aken
Untitled by Ann Harrington
And He Taketh Away by David Reed
Untitled by Mary Graham
Untitled by Melody A. Cummons
Untitled by Karen Blumberg
To The Poets by Judith Gallo
Untitled by Ann Harringto
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A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.
Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis
Do exercise interventions improve participation in life roles among older adults? A systematic review and meta-analysis
PenQuest Volume 2, Number 1
Table of Contents for this Volume:
Untitled by Janet Collins
Untitled by Judy Gozdur
Last Hour of Light by Susan Reed
Untitled by Judy Godzur
Untitled by Rick Wagner
Untitled by Carol Groover
Untitled by R. Wagner
Only in the Portico by Linda Banicki
Untitled by Helen Hagadorn
Private Place, Pubic Place by David Reed
Untitled by Tammy Hutchinson
Untitled by Tammy Hutchinson
Madison Knights by Susan Reed
Untitled by Sissy Crabtree
The Price by Sandra Coleman
Untitled by Ann Harrington
Invasion of Privacy by Mark Touchton
Untitled by Bruce Warner
Untitled by Tom Schifanella
Untitled by Tammy Hutchinson
Bloodwork by Laura Jo Last
Untitled by David Whitsett
Burial Instructions by Bill Slaughter
Untitled by S. Trevett
PenQuest Interview: Joe Haldeman by David Reed
Her Name Came from the Sea by Richard L. Ewart
Untitled by V. Williams
In the Woodshed by R. E. Mallery
Untitled by Modesta Matthews
Untitled by David Olson
Illumination by E. Allen Tilley
Untitled by Joseph Avanzini
Everywoman by Laura Jo Last
Untitled by Beth Goeckel
Believe Me by Donna Kaluzniak
Untitled by Judy Gozdur
Untitled by Judy Gozdur
Unicorn by David Reed
Untitled by Susan Reed
untitled by Paul Cramer
Unititled by Lucinda Halsema
The Violin by Richard L. Ewart
Untitled by Maria Barry
Untitled by Roger Whitt Jr.
Haiku by Lori Nasrallah
Rhymer’s Revolt by R. E. Mallery
Untitled by Valerie William
The morphology and biochemistry of nanostructures provide evidence for synthesis and signaling functions in human cerebrospinal fluid
<p>Abstract</p> <p>Background</p> <p>Cerebrospinal fluid (CSF) contacts many brain regions and may mediate humoral signaling distinct from synaptic neurotransmission. However, synthesis and transport mechanisms for such signaling are not defined. The purpose of this study was to investigate whether human CSF contains discrete structures that may enable the regulation of humoral transmission.</p> <p>Methods</p> <p>Lumbar CSF was collected prospectively from 17 participants: with no neurological or psychiatric disease, with Alzheimer's disease, multiple sclerosis, or migraine; and ventricular CSF from two cognitively healthy participants with long-standing shunts for congenital hydrocephalus. Cell-free CSF was subjected to ultracentrifugation to yield supernatants and pellets that were examined by transmission electron microscopy, shotgun protein sequencing, electrophoresis, western blotting, lipid analysis, enzymatic activity assay, and immuno-electron microscopy.</p> <p>Results</p> <p>Over 3,600 CSF proteins were identified from repeated shotgun sequencing of cell-free CSF from two individuals with Alzheimer's disease: 25% of these proteins are normally present in membranes. Abundant nanometer-scaled structures were observed in ultracentrifuged pellets of CSF from all 16 participants examined. The most common structures included synaptic vesicle and exosome components in 30-200 nm spheres and irregular blobs. Much less abundant nanostructures were present that derived from cellular debris. Nanostructure fractions had a unique composition compared to CSF supernatant, richer in omega-3 and phosphoinositide lipids, active prostanoid enzymes, and fibronectin.</p> <p>Conclusion</p> <p>Unique morphology and biochemistry features of abundant and discrete membrane-bound CSF nanostructures are described. Prostaglandin H synthase activity, essential for prostanoid production and previously unknown in CSF, is localized to nanospheres. Considering CSF bulk flow and its circulatory dynamics, we propose that these nanostructures provide signaling mechanisms <it>via </it>volume transmission within the nervous system that are for slower, more diffuse, and of longer duration than synaptic transmission.</p
Comparative Analysis of Serine/Arginine-Rich Proteins across 27 Eukaryotes: Insights into Sub-Family Classification and Extent of Alternative Splicing
Alternative splicing (AS) of pre-mRNA is a fundamental molecular process that generates diversity in the transcriptome and proteome of eukaryotic organisms. SR proteins, a family of splicing regulators with one or two RNA recognition motifs (RRMs) at the N-terminus and an arg/ser-rich domain at the C-terminus, function in both constitutive and alternative splicing. We identified SR proteins in 27 eukaryotic species, which include plants, animals, fungi and “basal” eukaryotes that lie outside of these lineages. Using RNA recognition motifs (RRMs) as a phylogenetic marker, we classified 272 SR genes into robust sub-families. The SR gene family can be split into five major groupings, which can be further separated into 11 distinct sub-families. Most flowering plants have double or nearly double the number of SR genes found in vertebrates. The majority of plant SR genes are under purifying selection. Moreover, in all paralogous SR genes in Arabidopsis, rice, soybean and maize, one of the two paralogs is preferentially expressed throughout plant development. We also assessed the extent of AS in SR genes based on a splice graph approach (http://combi.cs.colostate.edu/as/gmap_SRgenes). AS of SR genes is a widespread phenomenon throughout multiple lineages, with alternative 3′ or 5′ splicing events being the most prominent type of event. However, plant-enriched sub-families have 57%–88% of their SR genes experiencing some type of AS compared to the 40%–54% seen in other sub-families. The SR gene family is pervasive throughout multiple eukaryotic lineages, conserved in sequence and domain organization, but differs in gene number across lineages with an abundance of SR genes in flowering plants. The higher number of alternatively spliced SR genes in plants emphasizes the importance of AS in generating splice variants in these organisms
Genetic mechanisms of critical illness in COVID-19.
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 × 10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
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