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Objective To report on the presence and use of social media by speakers and attendees at the International Conference on Emergency Medicine (ICEM) 2012, and describe the increasing use of online technologies such as Twitter and podcasts in publicising conferences and sharing research findings, and for clinical teaching. Methods Speakers were identified through the organising committee and a database constructed using the internet to determine the presence and activity of speakers on social media platforms. We also examined the use of Twitter by attendees and non-attendees using an online archiving system. Researchers tracked and reviewed every tweet produced with the hashtag #ICEM2012. Tweets were then reviewed and classified by three separate authors into different categories. Results Of the 212 speakers at ICEM 2012, 41.5% had a LinkedIn account and 15.6% were on Twitter. Less than 1% were active on Google+ and less than 10% had an active website or blog. There were over 4500 tweets about ICEM 2012. Over 400 people produced tweets about the conference, yet only 34% were physically present at the conference. Of the original tweets produced, 74.4% were directly related to the clinical and research material of the conference. Conclusions ICEM 2012 was the most tweeted emergency medicine conference on record. Tweeting by participants was common; a large number of original tweets regarding clinical material at the conference were produced. There was also a large virtual participation in the conference as multiple people not attending the conference discussed the material on Twitter.

Disruptive technologies are revolutionising continuing professional development in emergency medicine and critical care (EMCC). Data on EMCC blogs and podcasts were gathered prospectively from 2002 through November 2013. During this time there was a rapid expansion of EMCC websites, from two blogs and one podcast in 2002 to 141 blogs and 42 podcasts in 2013. This paper illustrates the explosive growth of EMCC websites and provides a foundation that will anchor future research in this burgeoning field.

Bryant’s sign is defined as ecchymosis at the base of the penis and scrotum and is usually associated with a retroperitoneal bleed or ruptured aortic aneurysm. We report the case of a retroperitoneal paraduodenal bleed which presented with Bryant’s sign. Imaging confirmed a pancreaticoduodenal arcade microaneurysm and associated low-grade coeliac artery stenosis (Sutton-Kadir syndrome). Retroperitoneal bleeding can be life threatening and requires prompt diagnosis and management. However, diagnosis can be challenging due to the clinical variation in presentation. The rarity of presentation in this case caused significant uncertainty necessitating a multidisciplinary approach for diagnostic clarity and safe patient care.

Genome editing, specifically CRISPR/Cas9 technology, has revolutionized biomedical research and offers potential cures for genetic diseases. Despite rapid progress, low efficiency of targeted DNA integration and generation of unintended mutations represent major limitations for genome editing applications caused by the interplay with DNA double-strand break repair pathways. To address this, we conduct a large-scale compound library screen to identify targets for enhancing targeted genome insertions. Our study reveals DNA-dependent protein kinase (DNA-PK) as the most effective target to improve CRISPR/Cas9-mediated insertions, confirming previous findings. We extensively characterize AZD7648, a selective DNA-PK inhibitor, and find it to significantly enhance precise gene editing. We further improve integration efficiency and precision by inhibiting DNA polymerase theta (Polϴ). The combined treatment, named 2iHDR, boosts templated insertions to 80% efficiency with minimal unintended insertions and deletions. Notably, 2iHDR also reduces off-target effects of Cas9, greatly enhancing the fidelity and performance of CRISPR/Cas9 gene editing. Low efficiency of target DNA integration remains a challenge in genome engineering. Here the authors perform large-scale compound library and genetic screens to identify targets that enhance gene editing: they see that combined DNA-PK and Polϴ inhibition with potent compounds increases editing efficiency and precision.

Genome editing tools, especially CRISPR/Cas9-based strategies, have transformed biomedical research and opened opportunities for developing curative treatments for genetic diseases. Despite rapid progress, low efficiency of targeted DNA integration and generation of undesired mutations represent major limitations for genome editing applications. Both issues arise from the interplay between the main DNA Double-Strand Break (DSB) repair pathways, Homology-Directed Repair (HDR), Non-Homologous End Joining (NHEJ), and Microhomology-Mediated End Joining (MMEJ). To improve efficiencies of targeted CRISPR-Cas9 genome editing, we screened a large compound library. This led to the discovery of AZD7648, a DNA-dependent protein kinase (DNA-PK) inhibitor and potent enhancer of CRISPR-Cas9-mediated integration. We demonstrated that AZD7648 increased HDR and decreased mutagenic NHEJ repair, thus resulting in improved performance of precise gene editing. Furthermore, we observed additional improvement of integration efficiency by impairing MMEJ repair through DNA polymerase ϴ (Polϴ) inhibition. Combined treatment with AZD7648 and Polϴ inhibitors (which we named 2iHDR) substantially increased precision of templated insertions, with efficiencies of up to 80%, and nearly no formation of undesired Insertion-Deletions (InDels). Importantly, 2iHDR also decreased Cas9-associated off-target activity, dramatically improving the performance and fidelity of CRISPR-Cas9 gene editing.Competing Interest StatementS.W., N.A., M.F., J.B., S.E., A.L., P.H., S.L., S.C., J.S., B.B., B.S., B.M., S.DC., P.I., M.B., T.M., S.R., O.E., E.C., J.V.F., S.S., P.A., A.T.G. and M.M. are presently or were previously employed by AstraZeneca and may be AstraZeneca shareholders. M.K.S., M.R.S., and TM are presently employed by Promega Corporation.