Single neuron transcriptomics identify SRSF/ SR protein B52 as a regulator of axon growth and Choline acetyltransferase splicing.

We removed single identified neurons from living Drosophila embryos to gain insight into the transcriptional control of developing neuronal networks. The microarray analysis of the transcriptome of two sibling neurons revealed seven differentially expressed transcripts between both neurons (threshold: log(2)1.4). One transcript encodes the RNA splicing factor B52. Loss of B52 increases growth of axon branches. B52 function is also required for Choline acetyltransferase (ChAT ) splicing. At the end of embryogenesis, loss of B52 function impedes splicing of ChAT, reduces acetylcholine synthesis, and extends the period of uncoordinated muscle twitches during larval hatching. ChAT regulation by SRSF proteins may be a conserved feature since changes in SRSF5 expression and increased acetylcholine levels in brains of bipolar disease patients have been reported recently

State of the climate in 2017

In 2017, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-reached new record highs. The annual global average carbon dioxide concentration at Earth's surface for 2017 was 405.0 ± 0.1 ppm, 2.2 ppm greater than for 2016 and the highest in the modern atmospheric measurement record and in ice core records dating back as far as 800 000 years. The global growth rate of CO2 has nearly quadrupled since the early 1960s. With ENSO-neutral conditions present in the central and eastern equatorial Pacific Ocean during most of the year and weak La Niña conditions notable at the start and end, the global temperature across land and ocean surfaces ranked as the second or third highest, depending on the dataset, since records began in the mid-to-late 1800s. Notably, it was the warmest non-El Niño year in the instrumental record. Above Earth's surface, the annual lower tropospheric temperature was also either second or third highest according to all datasets analyzed. The lower stratospheric temperature was about 0.2°C higher than the record cold temperature of 2016 according to most of the in situ and satellite datasets. Several countries, including Argentina, Uruguay, Spain, and Bulgaria, reported record high annual temperatures. Mexico broke its annual record for the fourth consecutive year. On 27 January, the temperature reached 43.4°C at Puerto Madryn, Argentina-the highest temperature recorded so far south (43°S) anywhere in the world. On 28 May in Turbat, western Pakistan, the high of 53.5°C tied Pakistan's all-time highest temperature and became the world-record highest temperature for May. In the Arctic, the 2017 land surface temperature was 1.6°C above the 1981-2010 average, the second highest since the record began in 1900, behind only 2016. The five highest annual Arctic temperatures have all occurred since 2007. Exceptionally high temperatures were observed in the permafrost across the Arctic, with record values reported in much of Alaska and northwestern Canada. In August, high sea surface temperature (SST) records were broken for the Chukchi Sea, with some regions as warm as +11°C, or 3° to 4°C warmer than the longterm mean (1982-present). According to paleoclimate studies, today's abnormally warm Arctic air and SSTs have not been observed in the last 2000 years. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 7 March, sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, covering 8% less area than the 1981-2010 average. The Arctic sea ice minimum on 13 September was the eighth lowest on record and covered 25% less area than the long-term mean. Preliminary data indicate that glaciers across the world lost mass for the 38th consecutive year on record; the declines are remarkably consistent from region to region. Cumulatively since 1980, this loss is equivalent to slicing 22 meters off the top of the average glacier. Antarctic sea ice extent remained below average for all of 2017, with record lows during the first four months. Over the continent, the austral summer seasonal melt extent and melt index were the second highest since 2005, mostly due to strong positive anomalies of air temperature over most of the West Antarctic coast. In contrast, the East Antarctic Plateau saw record low mean temperatures in March. The year was also distinguished by the second smallest Antarctic ozone hole observed since 1988. Across the global oceans, the overall long-term SST warming trend remained strong. Although SST cooled slightly from 2016 to 2017, the last three years produced the three highest annual values observed; these high anomalies have been associated with widespread coral bleaching. The most recent global coral bleaching lasted three full years, June 2014 to May 2017, and was the longest, most widespread, and almost certainly most destructive such event on record. Global integrals of 0-700-m and 0-2000-m ocean heat content reached record highs in 2017, and global mean sea level during the year became the highest annual average in the 25-year satellite altimetry record, rising to 77 mm above the 1993 average. In the tropics, 2017 saw 85 named tropical storms, slightly above the 1981-2010 average of 82. The North Atlantic basin was the only basin that featured an above-normal season, its seventh most active in the 164-year record. Three hurricanes in the basin were especially notable. Harvey produced record rainfall totals in areas of Texas and Louisiana, including a storm total of 1538.7 mm near Beaumont, Texas, which far exceeds the previous known U.S. tropical cyclone record of 1320.8 mm. Irma was the strongest tropical cyclone globally in 2017 and the strongest Atlantic hurricane outside of the Gulf of Mexico and Caribbean on record with maximum winds of 295 km h-1. Maria caused catastrophic destruction across the Caribbean Islands, including devastating wind damage and flooding across Puerto Rico. Elsewhere, the western North Pacific, South Indian, and Australian basins were all particularly quiet. Precipitation over global land areas in 2017 was clearly above the long-term average. Among noteworthy regional precipitation records in 2017, Russia reported its second wettest year on record (after 2013) and Norway experienced its sixth wettest year since records began in 1900. Across India, heavy rain and flood-related incidents during the monsoon season claimed around 800 lives. In August and September, above-normal precipitation triggered the most devastating floods in more than a decade in the Venezuelan states of Bolívar and Delta Amacuro. In Nigeria, heavy rain during August and September caused the Niger and Benue Rivers to overflow, bringing floods that displaced more than 100 000 people. Global fire activity was the lowest since at least 2003; however, high activity occurred in parts of North America, South America, and Europe, with an unusually long season in Spain and Portugal, which had their second and third driest years on record, respectively. Devastating fires impacted British Columbia, destroying 1.2 million hectares of timber, bush, and grassland, due in part to the region's driest summer on record. In the United States, an extreme western wildfire season burned over 4 million hectares; the total costs of $18 billion tripled the previous U.S. annual wildfire cost record set in 1991

To see or not to see: investigating detectability of Ganges River dolphins using a combined visual-acoustic survey

Detection of animals during visual surveys is rarely perfect or constant, and failure to account for imperfect detectability affects the accuracy of abundance estimates. Freshwater cetaceans are among the most threatened group of mammals, and visual surveys are a commonly employed method for estimating population size despite concerns over imperfect and unquantified detectability. We used a combined visual-acoustic survey to estimate detectability of Ganges River dolphins (Platanista gangetica gangetica) in four waterways of southern Bangladesh. The combined visual-acoustic survey resulted in consistently higher detectability than a single observer-team visual survey, thereby improving power to detect trends. Visual detectability was particularly low for dolphins close to meanders where these habitat features temporarily block the view of the preceding river surface. This systematic bias in detectability during visual-only surveys may lead researchers to underestimate the importance of heavily meandering river reaches. Although the benefits of acoustic surveys are increasingly recognised for marine cetaceans, they have not been widely used for monitoring abundance of freshwater cetaceans due to perceived costs and technical skill requirements. We show that acoustic surveys are in fact a relatively cost-effective approach for surveying freshwater cetaceans, once it is acknowledged that methods that do not account for imperfect detectability are of limited value for monitoring

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Spontaneous Breathing in Early Acute Respiratory Distress Syndrome: Insights From the Large Observational Study to UNderstand the Global Impact of Severe Acute Respiratory FailurE Study

OBJECTIVES: To describe the characteristics and outcomes of patients with acute respiratory distress syndrome with or without spontaneous breathing and to investigate whether the effects of spontaneous breathing on outcome depend on acute respiratory distress syndrome severity. DESIGN: Planned secondary analysis of a prospective, observational, multicentre cohort study. SETTING: International sample of 459 ICUs from 50 countries. PATIENTS: Patients with acute respiratory distress syndrome and at least 2 days of invasive mechanical ventilation and available data for the mode of mechanical ventilation and respiratory rate for the 2 first days. INTERVENTIONS: Analysis of patients with and without spontaneous breathing, defined by the mode of mechanical ventilation and by actual respiratory rate compared with set respiratory rate during the first 48 hours of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Spontaneous breathing was present in 67% of patients with mild acute respiratory distress syndrome, 58% of patients with moderate acute respiratory distress syndrome, and 46% of patients with severe acute respiratory distress syndrome. Patients with spontaneous breathing were older and had lower acute respiratory distress syndrome severity, Sequential Organ Failure Assessment scores, ICU and hospital mortality, and were less likely to be diagnosed with acute respiratory distress syndrome by clinicians. In adjusted analysis, spontaneous breathing during the first 2 days was not associated with an effect on ICU or hospital mortality (33% vs 37%; odds ratio, 1.18 [0.92-1.51]; p = 0.19 and 37% vs 41%; odds ratio, 1.18 [0.93-1.50]; p = 0.196, respectively ). Spontaneous breathing was associated with increased ventilator-free days (13 [0-22] vs 8 [0-20]; p = 0.014) and shorter duration of ICU stay (11 [6-20] vs 12 [7-22]; p = 0.04). CONCLUSIONS: Spontaneous breathing is common in patients with acute respiratory distress syndrome during the first 48 hours of mechanical ventilation. Spontaneous breathing is not associated with worse outcomes and may hasten liberation from the ventilator and from ICU. Although these results support the use of spontaneous breathing in patients with acute respiratory distress syndrome independent of acute respiratory distress syndrome severity, the use of controlled ventilation indicates a bias toward use in patients with higher disease severity. In addition, because the lack of reliable data on inspiratory effort in our study, prospective studies incorporating the magnitude of inspiratory effort and adjusting for all potential severity confounders are required

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database

Background: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). Methods: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. Results: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. Conclusions: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. Trial registration: NCT02010073. Registered on 12 December 2013

Epidemiology and patterns of tracheostomy practice in patients with acute respiratory distress syndrome in ICUs across 50 countries

Background: To better understand the epidemiology and patterns of tracheostomy practice for patients with acute respiratory distress syndrome (ARDS), we investigated the current usage of tracheostomy in patients with ARDS recruited into the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG-SAFE) study. Methods: This is a secondary analysis of LUNG-SAFE, an international, multicenter, prospective cohort study of patients receiving invasive or noninvasive ventilation in 50 countries spanning 5 continents. The study was carried out over 4 weeks consecutively in the winter of 2014, and 459 ICUs participated. We evaluated the clinical characteristics, management and outcomes of patients that received tracheostomy, in the cohort of patients that developed ARDS on day 1-2 of acute hypoxemic respiratory failure, and in a subsequent propensity-matched cohort. Results: Of the 2377 patients with ARDS that fulfilled the inclusion criteria, 309 (13.0%) underwent tracheostomy during their ICU stay. Patients from high-income European countries (n = 198/1263) more frequently underwent tracheostomy compared to patients from non-European high-income countries (n = 63/649) or patients from middle-income countries (n = 48/465). Only 86/309 (27.8%) underwent tracheostomy on or before day 7, while the median timing of tracheostomy was 14 (Q1-Q3, 7-21) days after onset of ARDS. In the subsample matched by propensity score, ICU and hospital stay were longer in patients with tracheostomy. While patients with tracheostomy had the highest survival probability, there was no difference in 60-day or 90-day mortality in either the patient subgroup that survived for at least 5 days in ICU, or in the propensity-matched subsample. Conclusions: Most patients that receive tracheostomy do so after the first week of critical illness. Tracheostomy may prolong patient survival but does not reduce 60-day or 90-day mortality. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013