Canonical A-to-I and C-to-U RNA Editing Is Enriched at 3′UTRs and microRNA Target Sites in Multiple Mouse Tissues

RNA editing is a process that modifies RNA nucleotides and changes the efficiency and fidelity of the central dogma. Enzymes that catalyze RNA editing are required for life, and defects in RNA editing are associated with many diseases. Recent advances in sequencing have enabled the genome-wide identification of RNA editing sites in mammalian transcriptomes. Here, we demonstrate that canonical RNA editing (A-to-I and C-to-U) occurs in liver, white adipose, and bone tissues of the laboratory mouse, and we show that apparent non-canonical editing (all other possible base substitutions) is an artifact of current high-throughput sequencing technology. Further, we report that high-confidence canonical RNA editing sites can cause non-synonymous amino acid changes and are significantly enriched in 3′ UTRs, specifically at microRNA target sites, suggesting both regulatory and functional consequences for RNA editing

Levers and leverage points for pathways to sustainability

Humanity is on a deeply unsustainable trajectory. We are exceeding planetary boundaries and unlikely to meet many international sustainable development goals and global environmental targets. Until recently, there was no broadly accepted framework of interventions that could ignite the transformations needed to achieve these desired targets and goals. As a component of the IPBES Global Assessment, we conducted an iterative expert deliberation process with an extensive review of scenarios and pathways to sustainability, including the broader literature on indirect drivers, social change and sustainability transformation. We asked, what are the most important elements of pathways to sustainability? Applying a social–ecological systems lens, we identified eight priority points for intervention (leverage points) and five overarching strategic actions and priority interventions (levers), which appear to be key to societal transformation. The eight leverage points are: (1) Visions of a good life, (2) Total consumption and waste, (3) Latent values of responsibility, (4) Inequalities, (5) Justice and inclusion in conservation, (6) Externalities from trade and other telecouplings, (7) Responsible technology, innovation and investment, and (8) Education and knowledge generation and sharing. The five intertwined levers can be applied across the eight leverage points and more broadly. These include: (A) Incentives and capacity building, (B) Coordination across sectors and jurisdictions, (C) Pre-emptive action, (D) Adaptive decision-making and (E) Environmental law and implementation. The levers and leverage points are all non-substitutable, and each enables others, likely leading to synergistic benefits. Transformative change towards sustainable pathways requires more than a simple scaling-up of sustainability initiatives—it entails addressing these levers and leverage points to change the fabric of legal, political, economic and other social systems. These levers and leverage points build upon those approved within the Global Assessment's Summary for Policymakers, with the aim of enabling leaders in government, business, civil society and academia to spark transformative changes towards a more just and sustainable world. A free Plain Language Summary can be found within the Supporting Information of this article.Fil: Chan, Kai M. A.. University of British Columbia; CanadáFil: Boyd, David R.. University of British Columbia; CanadáFil: Gould, Rachelle. University of Vermont; Estados UnidosFil: Jetzkowitz, Jens. Staatliches Museum fur Naturkunde Stuttgart; AlemaniaFil: Liu, Jianguo. Michigan State University; Estados UnidosFil: Muraca, Bárbara. University of Oregon; Estados UnidosFil: Naidoo, Robin. University of British Columbia; CanadáFil: Beck, Paige. University of British Columbia; CanadáFil: Satterfield, Terre. University of British Columbia; CanadáFil: Selomane, Odirilwe. Stellenbosch University; SudáfricaFil: Singh, Gerald G.. University of British Columbia; CanadáFil: Sumaila, Rashid. University of British Columbia; CanadáFil: Ngo, Hien T.. Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services; AlemaniaFil: Boedhihartono, Agni Klintuni. University of British Columbia; CanadáFil: Agard, John. The University Of The West Indies; Trinidad y TobagoFil: de Aguiar, Ana Paula D.. Stockholms Universitet; SueciaFil: Armenteras, Dolors. Universidad Nacional de Colombia; ColombiaFil: Balint, Lenke. BirdLife International; Reino UnidoFil: Barrington-Leigh, Christopher. Mcgill University; CanadáFil: Cheung, William W. L.. University of British Columbia; CanadáFil: Díaz, Sandra Myrna. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Driscoll, John. University of British Columbia; CanadáFil: Esler, Karen. Stellenbosch University; SudáfricaFil: Eyster, Harold. University of British Columbia; CanadáFil: Gregr, Edward J.. University of British Columbia; CanadáFil: Hashimoto, Shizuka. The University Of Tokyo; JapónFil: Hernández Pedraza, Gladys Cecilia. The World Economy Research Center; CubaFil: Hickler, Thomas. Goethe Universitat Frankfurt; AlemaniaFil: Kok, Marcel. PBL Netherlands Environmental Assessment Agency; Países BajosFil: Lazarova, Tanya. PBL Netherlands Environmental Assessment Agency; Países BajosFil: Mohamed, Assem A. A.. Central Laboratory for Agricultural Climate; EgiptoFil: Murray-Hudson, Mike. University Of Botswana; BotsuanaFil: O'Farrell, Patrick. University of Cape Town; SudáfricaFil: Palomo, Ignacio. Basque Centre for Climate Change; EspañaFil: Saysel, Ali Kerem. Boğaziçi University; TurquíaFil: Seppelt, Ralf. Martin-universität Halle-wittenberg; AlemaniaFil: Settele, Josef. German Centre for Integrative Biodiversity Research-iDiv; AlemaniaFil: Strassburg, Bernardo. International Institute for Sustainability, Estrada Dona Castorina; BrasilFil: Xue, Dayuan. Minzu University Of China; ChinaFil: Brondízio, Eduardo S.. Indiana University; Estados Unido

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

More than just a bracelet: the use of material symbolism to communicate love

There is growing recognition of the place of love in residential care for children (Smith, 2009). This paper is a critical analysis of a range of existing research on residential child care as well as studies of material culture and of care relationships more broadly. It argues that, despite increasing regulation and surveillance, adults and children find ways to show and feel love in the context of residential care. Whilst love may be regarded as something to be avoided or indeed prohibited in an adult/child care setting these deep bonds find expression in the everyday life of the children's home. By looking at love in this embodied way, the 'realness' of material things to assert connection and recognition of love (Layne, 2000) is examined. As Gorenstein (1996, p.8) suggests 'objects...[are] the perfect vehicles for conveying themes that are not commonly accepted in a community'. The paper emphasises the recognition of these symbolic and metaphorical forms of communication in practice

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Imaging-Ambiguous Lesions of Meckel\u27s Cave-Utility of Endoscopic Endonasal Transpterygoid Biopsy.

INTRODUCTION: Meckel\u27s cave is a dural-lined cavity in the middle fossa skull base in which lies the Gasserian ganglion, a potential site for tumors and inflammatory lesions. A variety of lesions can be predominantly isolated to Meckel\u27s cave, including extension from head and neck cancers, other malignant tumors, as well as benign lesions. Clinical presentation and imaging findings are often insufficient to establish a diagnosis. Hence, histologic confirmation is required to determine the appropriate treatment strategy. Several surgical approaches have been used to reach this deep-seated area, often with significant morbidity and prolonged recovery. Given advancements in endoscopy and greater facility with the technique, the endoscopic endonasal approach has been used increasingly to reach lesions in the region. METHODS: A single-institution, retrospective chart review over a 10-year period was performed to identify and describe patients with pathologically differing but imaging-similar lesions with their epicenter in Meckel\u27s cave. RESULTS: Of a total of 21 cases of lesions in Meckel\u27s cave approached by an endoscopic endonasal transpterygoid approach, we present 6 patients with imaging-ambiguous lesions involving Meckel\u27s cave that were biopsied via the extended endoscopic endonasal approach. Among this diverse group, pathology included B-cell lymphoma, squamous cell carcinoma, adenocarcinoma, malignant schwannoma, benign schwannoma, and neurosarcoidosis. CONCLUSIONS: We explore not only the relevance of this approach in the armamentarium of the modern skull-base surgeon but also its limitations and conclude that the endoscopic endonasal approach provides a safe and relatively direct, minimally invasive corridor to many lesions of Meckel\u27s cave