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Sharing information about learners during training is seen as an important component supporting learner progression and relevant to patient safety. Shared information may cover topics from accommodation requirements to unprofessional behavior. The purpose of this study was to determine the views of key stakeholders on a proposed national information sharing process during the transition from undergraduate to postgraduate medical education in Canada, termed the Learner Education Handover (LEH).doi:10.1186/s12909-019-1598-7 pmid:31096966 pmcid:PMC6524250 fatcat:gx6bkiz35jb7hnajo5osdkzbq4
more »... ey stakeholder groups including medical students, resident physicians, residency program directors, medical regulatory authority representatives, undergraduate medical education deans, student affairs leaders, postgraduate medical education deans participated in focus groups conducted via teleconference. Data were transcribed and coded independently by two coders, then analyzed for themes informed by principles of constructivist grounded theory. Sixty participants (33 males and 27 females) from 16 focus groups representing key stakeholder groups participated. Most recognized value in a national LEH that would facilitate a smooth learner transition from medical school to residency. Potential risks and benefits of the LEH were identified. Themes significant to the content, process and format of the LEH also emerged. Guiding principles of the LEH process were determined to include that it be learner-centered while supporting patient safety, resident wellness and professional behavior. The learner and representatives from their undergraduate medical education environment would each contribute to the LEH. The LEH must advocate for the learner with respect for learner privacy, while promoting professionalism, patient safety and learner wellness.
Myopia, or short-sightedness, is one of the leading causes of visual disability in the World. The prevalence of myopia has risen steadily over recent decades, reaching epidemic levels in Southeast Asia. Observational studies have reported associations between educational attainment and myopia. Whether education causes myopia, myopic children are more intelligent, or another factor, like higher socioeconomic status, causes both is unclear since observational studies are prone to confounding anddoi:10.1101/172247 fatcat:2j6zcoqduzbfbjh7zi27ga5yqy
more »... andomised trials of education are unethical. Using bidirectional Mendelian Randomisation, a form of instrumental variable (IV) analysis free from confounding, we show that every additional year in education leads to an increase in myopic refractive error, but that myopia does not lead to higher educational attainment. Our results suggest that current educational methods contribute to the global burden of myopia, and argue that educational policies and practices should take account of this to reduce future visual disability in the population.
Woods 1 , Edward Mountjoy 1,2 , Duncan Muir 1 , Sarah E. Ross 3 & Denize Atan 1 Figure 1 . 1 The adult rod bipolar cell transcriptome regulates synaptic structure and signalling. ...doi:10.1038/s41598-018-23901-6 pmid:29615777 pmcid:PMC5883057 fatcat:kjlvlwaxbndj5irud33nzv2t54
Journal of Virology
Mouse bioassay remains the gold standard for determining proof of infectivity, strain type, and infectious titer estimation in prion disease research. The development of an approach using ex vivo cell-based assays remains an attractive alternative, both in order to reduce the use of mice and to hasten results. The main limitation of a cell-based approach is the scarcity of cell lines permissive to infection with natural transmissible spongiform encephalopathy strains. This study combines twodoi:10.1128/jvi.01855-09 pmid:20032176 pmcid:PMC2820909 fatcat:dsrvlk2q2rbszkvqz5c362rfvm
more »... ances in this area, namely, the standard scrapie cell assay (SSCA) and the Rov9 and MovS6 cell lines, which both express the ovine PrP VRQ allele, to assess to what extent natural and experimental ovine scrapie can be detected ex vivo. Despite the Rov9 and MovS6 cell lines being of different biological origin, they were both permissive and resistant to infection with the same isolates of natural sheep scrapie as detected by SSCA. Rov9 subclones that are 20 times more sensitive than Rov9 to SSBP/1-like scrapie infection were isolated, but all the subclones maintained their resistance to isolates that failed to transmit to the parental line. The most sensitive subclone of the Rov9 cell line was used to estimate the infectious titer of a scrapie brain pool (RBP1) and proved to be more sensitive than the mouse bioassay using wild-type mice. Increasing the sensitivity of the Rov9 cell line to SSBP/1 infection did not correlate with broadening susceptibility, as the specificity of permissiveness and resistance to other scrapie isolates was maintained.
To determine whether more years spent in education is a causal risk factor for myopia, or whether myopia is a causal risk factor for more years in education.doi:10.1136/bmj.k2022 pmid:29875094 pmcid:PMC5987847 fatcat:6kgxdnlnorgvhfdkplhygimvpu
Distinct signaling pathways are reported to maintain pluripotency in embryo-derived stem cells. Mouse embryonic stem cells (ESCs) respond to leukemia inhibitory factor (LIF) and bone morphogenetic protein (BMP)mediated activity, whereas human ESCs depend upon Fibroblast growth factor (FGF) and activin signaling. In the majority of mammals investigated, however, the signals that support stem cell pluripotency are not well defined, as is evident by the persistent difficulties in maintainingdoi:10.1089/cell.2011.0078 pmid:22339199 fatcat:2lveevqwyzaitltqs2hmgqk3ci
more »... tic stable ESC lines. Induction of pluripotency by transcription factor-mediated reprogramming could provide an alternative way to produce ESC-like cells from nonpermissive species, and facilitate identification of core ESC signaling requirements. To evaluate the effectiveness of this approach in pigs, we transduced porcine foetal fibroblasts with retroviruses expressing Oct4, Sox2, Klf4, and c-Myc, and maintained the resulting cultures in medium containing either LIF or FGF2. Alkaline phosphatase positive colonies with compact, mouse ESC-like morphology were preferentially recovered using serum-free medium supplemented with LIF. These cell lines expressed the endogenous stem cell transcription factors, OCT4, NANOG, and SOX2, and the cell surface marker SSEA-4, consistent with acquisition of an undifferentiated state. However, restricted differentiation potential, and persistent expression of retroviral transgenes indicated that reprogramming was incomplete. Interestingly, LIF activated both the transcription factor STAT3 and its target gene SOCS3, and stimulated cell growth, indicating functional coupling of the signaling pathway in these cells. This demonstration of LIF-dependence in reprogrammed pig cells supports the notion that the connection between LIF/STAT3 signaling and the core regulatory network of pluripotent stem cells is a conserved pathway in mammals.
Data from germline testing in unselected patients with hepatobiliary cancers are limited. Identification of germline predisposition can have important implications on cancer treatment and family counseling. To determine prevalence of pathogenic germline variants (PGV) in hepatobiliary cancer patients we undertook a prospective multi-site study of germline sequencing using a >80 gene next-generation sequencing platform among patients with hepatobiliary cancers receiving care at Mayo Clinicdoi:10.1158/1940-6207.capr-21-0189 pmid:34782326 fatcat:jtulskrfpzhrppmnf3sh5u62g4
more »... Centers between April 1, 2018 and March 31, 2020. Patients were not selected based on stage, family cancer history, ethnicity, or age. Family cascade testing was offered at no cost. Of 205 patients, the median age was 65 years, 58.5% were male, 81% were white, and 64.4% had cholangiocarcinoma, 21.5% hepatocellular carcinoma, 7.8% gallbladder cancer and 4.3% carcinoma of ampulla of Vater. PGV were found in 15.6% (n=32) of patients, including 23 (71%) in moderate and high penetrance cancer susceptibility genes. 75% of patients with a positive result would not have been detected using guidelines for genetic evaluation. Prevalence of PGV was 15.7% in intrahepatic cholangiocarcinoma, 17% in extrahepatic cholangiocarcinoma, 15.9% in hepatocellular cancer and 33% in carcinoma of ampulla of Vater. Based on these genetic findings, 55% were potentially eligible for approved precision therapy and/or clinical treatment trials. Universal multi-gene panel testing in hepatobiliary cancers was associated with detection of heritable mutations in over 15% of patients most of whom would not have been tested using current guidelines. Germline testing should be considered in all patients with hepatobiliary cancers.
The GWAS Catalog delivers a high-quality curated collection of all published genome-wide association studies enabling investigations to identify causal variants, understand disease mechanisms, and establish targets for novel therapies. The scope of the Catalog has also expanded to targeted and exome arrays with 1000 new associations added for these technologies. As of September 2018, the Catalog contains 5687 GWAS comprising 71673 variant-trait associations from 3567 publications. New contentdoi:10.1093/nar/gky1120 pmid:30445434 pmcid:PMC6323933 fatcat:vr33crty4bghhamnlzyjyh4zju
more »... cludes 284 full P-value summary statistics datasets for genome-wide and new targeted array studies, representing 6 × 109 individual variant-trait statistics. In the last 12 months, the Catalog's user interface was accessed by ∼90000 unique users who viewed >1 million pages. We have improved data access with the release of a new RESTful API to support high-throughput programmatic access, an improved web interface and a new summary statistics database. Summary statistics provision is supported by a new format proposed as a community standard for summary statistics data representation. This format was derived from our experience in standardizing heterogeneous submissions, mapping formats and in harmonizing content. Availability: https://www.ebi.ac.uk/gwas/.
The Open Targets Platform (https://www.targetvalidation.org/) provides users with a queryable knowledgebase and user interface to aid systematic target identification and prioritisation for drug discovery based upon underlying evidence. It is publicly available and the underlying code is open source. Since our last update two years ago, we have had 10 releases to maintain and continuously improve evidence for target–disease relationships from 20 different data sources. In addition, we havedoi:10.1093/nar/gkaa1027 pmid:33196847 fatcat:3qrm5q5turgulbvyj2kj6oy5c4
more »... rated new evidence from key datasets, including prioritised targets identified from genome-wide CRISPR knockout screens in 300 cancer models (Project Score), and GWAS/UK BioBank statistical genetic analysis evidence from the Open Targets Genetics Portal. We have evolved our evidence scoring framework to improve target identification. To aid the prioritisation of targets and inform on the potential impact of modulating a given target, we have added evaluation of post-marketing adverse drug reactions and new curated information on target tractability and safety. We have also developed the user interface and backend technologies to improve performance and usability. In this article, we describe the latest enhancements to the Platform, to address the fundamental challenge that developing effective and safe drugs is difficult and expensive.
Albuminuria is an independent risk factor for the progression to end-stage kidney failure, cardiovascular morbidity, and premature death. As such, discovering signaling pathways that modulate albuminuria is desirable. Here, we studied the transcriptomes of podocytes, key cells in the prevention of albuminuria, under diabetic conditions. We found that Neuropeptide Y (NPY) was significantly down-regulated in insulin-resistant vs. insulin-sensitive mouse podocytes and in human glomeruli ofdoi:10.1073/pnas.2004651117 pmid:32561647 fatcat:wlh4eboqbbafrawt2y4dnbmr3u
more »... with early and late-stage diabetic nephropathy, as well as other nondiabetic glomerular diseases. This contrasts with the increased plasma and urinary levels of NPY that are observed in such conditions. Studying NPY-knockout mice, we found that NPY deficiency in vivo surprisingly reduced the level of albuminuria and podocyte injury in models of both diabetic and nondiabetic kidney disease. In vitro, podocyte NPY signaling occurred via the NPY2 receptor (NPY2R), stimulating PI3K, MAPK, and NFAT activation. Additional unbiased proteomic analysis revealed that glomerular NPY-NPY2R signaling predicted nephrotoxicity, modulated RNA processing, and inhibited cell migration. Furthermore, pharmacologically inhibiting the NPY2R in vivo significantly reduced albuminuria in adriamycin-treated glomerulosclerotic mice. Our findings suggest a pathogenic role of excessive NPY-NPY2R signaling in the glomerulus and that inhibiting NPY-NPY2R signaling in albuminuric kidney disease has therapeutic potential.
The first Baron Mountjoy—of Thurveston, county Derby—was Lord High Treasurer of England, and received his title at the hands of Edward IV. on June 20, 1465. ... The Manor of Ludgvan Lees, near Penzance, was the marriage portion of Anne, second daughter of Edward, the only son of Robert, Lord Brooke—the wife of Charles Blount, fifth Lord Mountjoy. ...
Mountjoy Wm. J. Mountjoy Thos. Mountjoy John Mountjoy Gilbt. Campbell Jos. Lane John Beale junr. John Newton Will: Beale junr. Chs. Mortimer John Edmondson jr. ... Sanford Charles Chilton Edward Sanford Daniel McCarty Jer. Rush Edwd. Ransdell Townshend Dade John Ashton W. Brent Francis Foushee John Smith jour. Wm. Ball Thos. Barnes Jos. ...
The National and English Review
Probably also he is not aware that Sir Edward Maunde Thompson, who is certainly an “ expert,” and, perhaps, a “ Paleographer” too, has pronounced it an undoubted forgery! ... Where else could he have found the name of Mountjoy? ...
On the other hand, Roger Ludlow was not a descendant of Ralph, Earl of Westmoreland, and thus Edward III, for Anne (Neville) Mountjoy, the alleged ancestress of Roger and wife of Walter Lord Mountjoy, ... Roger Ludlow is a direct descendant of King Edward I. But first let us disentangle certain genealogical myths. ...
Notes and Queries
Walter Blunt, whom King Edward the, to the honour of Baron Mountjoy, with a pension. ... This family is noble and ancient, and greatly flourished at Kinlet in Shropshire; and by Elvaston in Derbyshire, where Sir Ralph Mountjoy had lands in the time of Edward the First; from whence came | Sir ...
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