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Fredrich is a transfusion safety and blood management officer for the Blood Center of Wisconsin in Milwaukee. The author has disclosed that she has no financial relationships related to this article. Research regarding the best use of transfusion of all types of blood components has grown over the last 20 years, resulting in numerous studies to support evidence-based practice in transfusion medicine. Current research has compared the use of transfusion thresholds or triggers in various patient populations and the effect of a restrictive or liberal strategy on patient outcomes, adverse events, and complications. M, 67, is admitted to the ICU with sepsis possibly related to diverticulitis and lower gastrointestinal (GI) bleeding. The healthcare provider (HCP) orders two units of packed red blood cells (RBCs) to be transfused for Mr. His wife indicated he had several black, tarry stools over the past 2 days and was complaining of shortness of breath, but no abdominal pain. M's hemoglobin (Hb) of 7.9 g/d L (normal in adult males, 14.0–17.4 g/d L) and hematocrit (Hct) of 25.2% (normal in adult males, 42%-52%). Anemia, a reduction in the number of circulating RBCs, can lead to a disruption in this gas exchange process. The objective of RBC transfusion is to increase the oxygen-carrying capacity by increasing the number of circulating RBCs. RBC transfusions are administered to replace RBCs lost due to: With growing emphasis on improving the quality of care provided to patients, blood transfusions have become an area of focus to not only improve patient care but as a cost-saving measure. This focus, known as PBM, has led to a critical review of transfusion practices and determination of best practices for evidence-based patient care. PBM is an evidence-based, multidisciplinary approach to optimizing the care of patients who might need a transfusion. Blood management goes beyond transfusions to include alternative treatment modalities that reduce the need for a transfusion. These strategies may incorporate medications to reduce blood loss, increase RBC production, or decrease RBC destruction and surgical techniques or equipment to minimize blood loss. In clinical practice, PBM includes weighing the risks, benefits, and alternatives of blood transfusion for each patient on an individual basis, which translates to a paradigm shift in transfusion practice, from “blood transfusions are not harmful” to “will this blood transfusion benefit this patient? ” Research regarding the best use of transfusion of all types of blood components has grown over the last 20 years, resulting in numerous studies to support evidence-based practice in transfusion medicine. Current research has compared the use of transfusion thresholds or triggers in various patient populations and the effect of a restrictive (Hb The multicenter study, known as the Transfusion Requirements In Critical Care (TRICC) trial, prospectively enrolled over 800 critically ill ICU patients who were randomized to either a restrictive (transfuse if Hb Multiple studies have been conducted since the TRICC trial comparing restrictive and liberal transfusion strategies. Study populations included patients undergoing cardiovascular surgery, those with septic shock, upper GI bleeding, abdominal cancer undergoing surgery, and hip fractures in older adults with cardiac risk factors. In a majority of the studies, the results supported the use of a restrictive transfusion strategy, which reduced the number of RBC transfusions without an increase in mortality or morbidity, functional recovery, or length of hospital stay. In patients undergoing hip fracture repair in the Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair trial, which was performed in patients with preexisting cardiovascular disease or risk factors, a restrictive transfusion strategy was associated with a nonstatistically significant higher risk of MI. enrolled patients with acute upper GI bleeding without signs and symptoms of shock. Researchers found that patients treated in restrictive strategy had fewer episodes of rebleeding and other in-hospital complications and an increased rate of survival. The reduction in rebleeding was thought to be due to reduction in pressure in the gut vasculature. This study involving patients with abdominal cancer requiring surgery and a postoperative stay in the ICU found that these patients had better outcomes with a more liberal transfusion strategy. A key strategy in blood management is transfusion of a single unit of RBCs with reassessment of the patient, including clinical signs and symptoms and Hb levels. This approach provides the minimal amount of RBC transfusions needed to resolve the patient's signs and symptoms. The traditional order to “transfuse 2 units RBCs” is becoming less common as awareness of PBM grows and research shows that fewer blood transfusions do not harm patients. As HCPs adopt this evidence-based practice and begin ordering single-unit RBC transfusions, nurses must support and promote this concept. Understanding the evidence and science behind the change builds a collaborative environment to improve patient care. Blood transfusions can save lives, but they can also cause adverse reactions. RBC transfusions are a “transplant” from a volunteer donor to a patient recipient. RBC transfusions are associated with an increase in mortality and healthcare-associated infections as well as an increased length of stay. The number of RBC units transfused was shown to be an independent risk factor for clinical complications or death at 30 days no matter the transfusion strategy. For each unit of RBCs transfused, the risk increased for respiratory, cardiac, renal, or infectious complications. According to the 2011 National Blood Collection & Utilization Survey, the rate of adverse events or transfusion reactions associated with a blood transfusion is 0.24% (2.4 per 1,000 transfusions) in the United States, which is well below the rate reported by national hemovigilance reporting systems in other countries. Mild reactions such as allergic or febrile, nonhemolytic transfusion reactions can occur as frequently as 1 to 4 reactions per 100 units transfused. Mild reactions are uncomfortable for the recipient and generally do not require extended hospitalization but, at times, medical intervention may be needed. Other reactions are more serious and may require transfer to a higher level of care. Transfusion-associated circulatory overload (TACO) or transfusion-related acute lung injury (TRALI) occurs less frequently but can extend a hospital stay and require medical interventions such as endotracheal intubation, mechanical ventilation, and fluid resuscitation and/or vasoactive support..) Recognizing the signs and symptoms of transfusion reactions and providing prompt intervention can reduce the severity of a reaction. Ideally, the decision for a blood transfusion is based on the clinical status of the patient, physical assessment findings, comorbidities, and lab values. (See Many patients in the ICU or hospital are anemic on admission due to acute blood loss, ongoing disease process, inflammation, or suppression of RBC production. Anemia can develop or worsen as a result of iatrogenic blood loss from phlebotomy or surgical blood loss. Response to changes in clinical status and loss of RBCs varies from patient to patient. (See Based on the AABB guidelines, the two-unit RBC transfusion ordered for Mr. His signs and symptoms included anemia and shortness of breath, so a single-unit RBC transfusion may have been beneficial. M received the first RBC transfusion would determine if a second unit was needed. Differentiating the signs and symptoms of anemia and hypovolemia can make it difficult to determine treatment options for patients. Use clinical assessment findings and other objective data rather than Hb values in isolation and collaborate with the HCP to determine the most effective treatment plan for the patient. If the answer to either of the first two questions is yes, a RBC transfusion is appropriate. Treatment of active bleeding involves controlling bleeding, replacement of fluids and blood, and other measures such as the administration of supplemental oxygen, to stabilize the patient. Prompt notification of the HCP and activation of the rapid response team are vital for effective treatment. For nonbleeding patients with signs such as hypotension or tachycardia unresponsive to fluid bolus, a single unit of RBCs could be considered. RBC transfusions may be appropriate, regardless of the Hb value, in any of the following situations: potential or ongoing blood loss, risk of inadequate oxygenation, or organ ischemia. In patients with preexisting cardiac disease including heart failure, consider transfusion for Hb and other physical assessment findings are essential for managing the care of patients during blood administration. If vital signs are stable (no hypotension, tachycardia, or hypoxemia), urine output is adequate, and the patient is participating in activities, a transfusion may not be needed. Changes in the patient's clinical status during the transfusion should be compared to baseline assessment data. In the event of inadequate urine output or hypotension, further investigation of the cause, notification of the HCP, and alternative therapy such as I. Include a review of the patient's health history, current I. infusion rates, and past 24-hour intake and output. Positive fluid balance, previous transfusion reactions, and comorbidities could indicate a risk for potential transfusion reactions such as a severe allergic reactions or TACO. Communicate any abnormal baseline assessment findings to the HCP prior to the start of a transfusion. Before requesting any blood product from the blood bank, ensure that the patient has a patent venous access with an appropriate blood administration set, provided informed consent, and received education about the transfusion. M has a history of heart failure, which places him at risk for possible TACO because each unit of RBCs contains approximately 350 m L. M's respiratory distress and hypoxemia were the result of a 2-unit transfusion given over 4 hours (total volume approximately 525 m L). Best practice is transfusion of a single RBC unit followed by patient reassessment including Hb determination prior to transfusing a second unit. Nursing interventions to reduce the incidence of TACO include slowing the rate of the transfusion, slowing or stopping other I. infusions, or administering diuretics as prescribed. If a patient experiences any signs or symptoms of a transfusion reaction during a transfusion, the first nursing action is always stopping the transfusion to reduce the severity of a suspected reaction, then reassessing the patient and notifying the HCP. Report all suspected transfusion reactions to the facility blood bank. Always follow facility policy and procedure for blood administration and reporting suspected transfusion reactions. If no improvement is seen, collaborate with the HCP to determine if a second RBC unit or other interventions and/or alternatives would benefit the patient. The best-practice guideline to follow when RBC transfusion is indicated is to administer one unit and reassess the patient. For the majority of nonbleeding symptomatic adult patients, a restrictive RBC transfusion strategy with a threshold of Hb 10. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. We’re taking added precautions to keep our clients and employees safe during the COVID-19 outbreak. We also recognize that now more than ever, clients turn to us for advice and support. Read More With more than 100 years of dedicated service to the Caribbean, RBC has a presence in 17 countries across the Caribbean, serving more than one million clients. As one of the Caribbean’s leading diversified financial services companies, RBC provides personal and commercial banking, wealth management, corporate and investment banking, insurance and trust and asset management services to a range of clients, including individuals, small businesses, general commercial entities, regional and multi-national corporations and governments. Rbc baseline rbc healthcare This file presents a baseline RBC model with TFP and government spending shocks, calibrated to US data from * 1947Q16Q1. The model setup is described in Handout_RBC_and resembles the one in King/Rebelo 1999 * Resuscitating Real Business Cycles, Handbook of Macroeconomics, Volume 1 and Whatever you need, RBC Royal Bank has a wide range of personal banking products, services and tools to help you manage your finances, save for retirement, buy a home and much more. Routing Number is used in Canada to identify the bank and the branch to which the payment is directed. Routing number for Royal Bank of Canada (RBC) have two formats:1. Paper Transaction Routing Number: Routing transit number for paper items (or MICR-encoded items) is in the format of XXXXX-YYY which is comprised of a five-digit branch transit number (XXXXX) and a three-digit financial institution number (YYY).2. Electronic Payments Routing Number: It's a 9 digit number which starts with 0 used for electronic fund transactions. If paper routing is XXXXX-YYY, then EFT routing number will be 0YYYXXXXX. Centrepointe Branch Bells Corners Branch Baseline & Merivale Branch Nepean-Strandherd & Cedarview BRRT-Centrepointe Br Woodroffe & Stranherd Br (Barrhaven) Bank of Montreal (1613) Bank of Nova Scotia (2185) Canadian Imperial Bank of Commerce (CIBC) (2114) CENTRAL 1 CREDIT UNION (1182) CREDIT UNION CENTRAL ALBERTA LIMITED (372) CREDIT UNION CENTRAL OF MANITOBA (224) CREDIT UNION CENTRAL OF SASKATCHEWAN (356) FEDERATION DES CAISSES DESJ. You may be able to find your test results on your laboratory's website or patient portal. You may have been directed here by your lab's website in order to provide you with background information about the test(s) you had performed. You will need to return to your lab's website or portal, or contact your healthcare practitioner in order to obtain your test results. Lab Tests Online is an award-winning patient education website offering information on laboratory tests. The content on the site, which has been reviewed by laboratory scientists and other medical professionals, provides general explanations of what results might mean for each test listed on the site, such as what a high or low value might suggest to your healthcare practitioner about your health or medical condition. The reference ranges for your tests can be found on your laboratory report. They are typically found to the right of your results. If you do not have your lab report, consult your healthcare provider or the laboratory that performed the test(s) to obtain the reference range. Laboratory test results are not meaningful by themselves. Their meaning comes from comparison to reference ranges. Reference ranges are the values expected for a healthy person. By comparing your test results with reference values, you and your healthcare provider can see if any of your test results fall outside the range of expected values. Available online at https://gov/pmc/articles/PMC4631707/. Values that are outside expected ranges can provide clues to help identify possible conditions or diseases. While accuracy of laboratory testing has significantly evolved over the past few decades, some lab-to-lab variability can occur due to differences in testing equipment, chemical reagents, and techniques. Pharm GKB Summary: Succinylcholine Pathway, Pharmacokinetics/Pharmacodynamics. This is a reason why so few reference ranges are provided on this site. It is important to know that you must use the range supplied by the laboratory that performed your test to evaluate whether your results are "within normal limits." For more information, please read the article Reference Ranges and What They Mean. Cholinesterases are enzymes that are involved in helping the nervous system to function properly. There are two separate cholinesterase enzymes in the body: (1) acetylcholinesterase, found in red blood cells as well as in the lungs, spleen, nerve endings, and the gray matter of the brain, and (2) pseudocholinesterase (butyrylcholinesterase), found in the serum as well as the liver, muscle, pancreas, heart, and white matter of the brain. Cholinesterase tests measure the activity of these enzymes. Acetylcholinesterase is involved in transmission of nerve impulses by breaking down acetylcholine, a chemical that helps to transmit signals across nerve endings. A decrease in the activity of the enzyme acetylcholinesterase results in excess acetylcholine at nerve endings. This can lead to overstimulation of nerves within body tissues and organs. Pseudochlinesterase is involved in processing and metabolizing drugs. The two most common reasons for testing activity levels in the blood are: Pre-operative screening for pseudocholinesterase activity is advised if a person or a close relative has experienced prolonged paralysis and apnea after the use of succinylcholine for anesthesia during an operation. Available online at https://medlineplus.gov/ency/article/003358 Described in: Field measurement of plasma and erythrocyte cholinesterases. A detailed case of two severely intoxicated patients monitored for ACh E, from initial insult through recovery. Delayed recovery from paralysis associated with plasma cholinesterase deficiency. Sources Used in Previous Reviews Ralph Magnotti, Ph D, DABCC. Magnotti RA, Dowling K, Eberly JP, Mc Connell RS (1988). Tietz Clinical Guide to Laboratory Tests, 4th Edition: Saunders Elsevier, St. Available online at https://gov/pmc/articles/PMC5084105/ Accessed on 6/25/17. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Unit Code 8767: Pseudocholinesterase, Dibucaine Inhibition, Serum. Recognition and Management of Pesticide Poisonings, Organophosphate Insecticides. PCHES - Clinical: Pseudocholinesterase, Total, Serum.

A complete blood count (CBC) is a test that counts the cells that make up your blood: red blood cells, white blood cells, and platelets. Your doctor may order a CBC as part of a routine checkup or to: If the CBC is the only blood test you’re having, you can eat and drink like you usually would. Your part of the test is simple and takes just a few minutes. A nurse or lab tech will take a sample of blood by putting a needle into a vein in your arm. Afterward, you can leave and get back to your routine. When you get your report, you’ll see two columns: a “reference range” and your results. If your results are inside the reference range, they’re considered normal. If your results are higher or lower than the reference range, they’re abnormal. Mild anemia is one of the most common reasons your results might be off. Each lab has different ways of studying your blood. So the reference range will depend on the lab that handles your blood tests. It’s also based on things that can affect your blood like your age, your sex, and how high above sea level you live. The European Train Control System (ETCS) is the signalling and control component of the European Rail Traffic Management System (ERTMS). It is a replacement for legacy train protection systems and designed to replace the many incompatible safety systems currently used by European railways. The standard was also adopted outside Europe and is an option for worldwide application. In technical terms it is a kind of positive train control. ETCS is implemented with standard trackside equipment and unified controlling equipment within the train cab. In its advanced form, all lineside information is passed to the driver wireless inside the cab, removing the need for lineside signals watched by the driver. This will give the foundation for a later to be defined automatic train operation. Trackside equipment aims to exchange information with the vehicle for safely supervising train circulation. The need for a system like ETCS stems from more and longer running trains resulting from economic integration of the European Union (EU) and the liberalisation of national railway markets. At the beginning of the 1990s there were some national high speed train projects supported by the EU which lacked interoperability of trains. This catalysed the Directive 1996/48 about the interoperability of high-speed trains, followed by Directive 2001/16 extending the concept of interoperability to the conventional rail system. ETCS specifications have become part of, or are referred to, the Technical Specifications for Interoperability (TSI) for (railway) control-command systems, pieces of European legislation managed by the European Union Agency for Railways (ERA). It is a legal requirement that all new, upgraded or renewed tracks and rolling stock in the European railway system should adopt ETCS, possibly keeping legacy systems for backward compatibility. Many networks outside the EU have also adopted ETCS, generally for high-speed rail projects. The main goal of achieving interoperability had mixed success in the beginning. Deployment has been slow, as there is no business case for replacing existing train protection systems, especially in Germany and France which already had advanced train protection systems installed in most mainlines. Even though these legacy systems were developed in the 1960s, they provided similar performance to ETCS Level 2, thus the reluctance of infrastructure managers to replace these systems with ETCS. There are also significant problems regarding compatibility of the latest software releases or baselines of infrastructure-side equipment with older on-board equipment, forcing in many cases the train operating companies to replace ETCS equipment after only a few years. Switzerland, an early adopter of ETCS Limited Supervision, has introduced a moratorium on its planned roll-out of ETCS Level 2 due to cost and capacity concerns, added to fears about GSM-R obsolence starting in 2030. The European railway network grew from separate national networks with little more in common than standard gauge. Notable differences include voltages, loading gauge, couplings, signalling and control systems. By the end of the 1980s there were 14 national standard train control systems in use across the EU, and the advent of high-speed trains showed that signalling based on lineside signals is insufficient. Both factors led to efforts to reduce the time and cost of cross-border traffic. On 4 and 5 December 1989, a working group including Transport Ministers resolved a master plan for a trans-European high-speed rail network, the first time that ETCS was suggested. The Commission communicated the decision to the European Council, which approved the plan in its resolution of 17 December 1990. This led to a resolution on 91/440/EEC as of 29 July 1991, which mandated the creation of a requirements list for interoperability in high-speed rail transport. Until 1993 the organizational framework was created to start technical specifications that would be published as Technical Specifications for Interoperability (TSI). Because ETCS is in many parts implemented in software, some wording from software technology is used. Versions are called system requirements specifications (SRS). This is a bundle of documents, which may have different versioning for each document. The specification was written in 1996 in response to EU Council Directive 96/48/EC99 of 23 July 1996 on interoperability of the trans-European high-speed rail system. First the European Railway Research Institute was instructed to formulate the specification and about the same time the ERTMS User Group was formed from six railway operators that took over the lead role in the specification. The standardisation went on for the next two years and it was felt to be slow for some industry partners – 1998 saw the formation of Union of Signalling Industry (UNISIG), including Alstom, Ansaldo, Bombardier, Invensys, Siemens and Thales that were to take over the finalisation of the standard. In July 1998 SRS 5a documents were published that formed the first baseline for technical specifications. UNISIG provided for corrections and enhancements of the baseline specification leading to the Class P specification in April 1999. The railway companies defined some extended requirements that were included to ETCS (e.g. RBC-Handover and track profile information), leading to the Class 1 SRS 2.0.0 specification of ETCS (published in April 2000). Further specification continued through a number of drafts until UNISIG published the SUBSET-026 defining the current implementation of ETCS signalling equipment – this Class 1 SRS 2.2.2 was accepted by the European Commission in decision 2002/731/EEC as mandatory for high-speed rail and in decision 2004/50/EEC as mandatory for conventional rail. The SUBSET-026 is defined from eight chapters where chapter seven defines the ETCS language and chapter eight describes the balise telegram structure of ETCS Level 1. The earlier ETCS specification contained a lot of optional elements that limited interoperability. The Class 1 specifications were revised in the following year leading to SRS 2.3.0 document series that was made mandatory by the European Commission in decision 2007/153/EEC on 9 March 2007. Annex A describes the technical specifications on interoperability for high-speed (HS) and conventional rail (CR) transport. Using SRS 2.3.0 a number of railway operators started to deploy ETCS on a large scale, for example the Italian Sistema Controllo Marcia Treno (SCMT) is based on Level 1 balises. Further development concentrated on compatibility specification with the earlier Class B systems leading to specifications like Euro ZUB that continued to use the national rail management on top of Eurobalises for a transitional period. Following the experience in railway operation the European Union Agency for Railways (ERA) published a revised specification Class 1 SRS 2.3.0d ("debugged") that was accepted by the European Commission in April 2008. This compilation SRS 2.3.0d was declared final (later called Baseline 2) in this series. There were a list of unresolved functional requests and a need for stability in practical rollouts. So in parallel started the development of baseline 3 series to incorporate open requests, strip off unneeded stuff and combine it with solutions found for baseline 2. While some countries switched to ETCS with some benefit, German and French railway operators had already introduced modern types of train protection systems so they would gain no benefit. Instead, ideas were introduced on new modes like "Limited Supervision" (known at least since 2004 These ideas were compiled into a "baseline 3" series by the ERA and published as a Class 1 SRS 3.0.0 proposal on 23 December 2008. The first consolidation SRS 3.1.0 of the proposal was published by ERA on 26 February 2010 The German Deutsche Bahn has since announced equipping at least the TEN Corridors running on older tracks to be using either Level 1 Limited Supervision or Level 2 on high-speed sections. Current work continues on Level 3 definition with low-cost specifications (compare ERTMS Regional) and the integration of GPRS into the radio protocol to increase the signalling bandwidth as required in shunting stations. The specifications for ETCS baseline 3 and GSM-R baseline 0 (Baseline 3 Maintenance Release 1) were published as recommendations SRS 3.4.0 by the ERA in May 2014 for submission to the Railway Interoperability and Safety Committee (RISC) in a meeting in June 2014. Stakeholders such as Deutsche Bahn have opted for a streamlined development model for ETCS – DB will assemble a database of change requests (CRs) to be assembled by priority and effect in a CR-list for the next milestone report (MRs) that shall be published on fixed dates through ERA. The SRS 3.4.0 from Q2 2014 matches with the MR1 from this process. The further steps were planned for the MR2 to be published in Q4 2015 (that became the SRS 3.5.0) and the MR3 to be published in Q3 2017 (whereas SRS 3.6.0 was settled earlier in June 2016). Each specification will be commented on and handed over to the RISC for subsequent legalization in the European Union. Deutsche Bahn has expressed a commitment to keep the Baseline 3 specification backward compatible starting at least with SRS 3.5.0 that is due in 2015 according to the streamlined MR2 process, with the MR1 adding requirements from its tests in preparation for the switch to ETCS (for example better frequency filters for the GSM-R radio equipment). The intention is based on plans to start replacing its PZB train protection system at the time. In December 2015 the ERA published the Baseline 3 Release 2 (B3R2) series including GSM-R Baseline 1. The B3R2 is publicly named to be not an update to the previous Baseline 3 Maintenance Release 1 (B3MR1). The notable change is the inclusion of EGPRS (GPRS with mandatory EDGE support) in the GSM-R specification, corresponding to the new Eirene FRS 8 / SRS 16 specifications. Additionally B3R2 includes the ETCS Driver Machine Interface and the SRS 3.5.0. The name of Set 3 follows the style of publications of the decisions of the European Commission where updates to the Baseline 2 and Baseline 3 specifications were accepted at the same time – for example decision 2015/14/EU of January 2015 has two tables "Set of specifications # 1 (ETCS baseline 2 and GSM-R baseline 0)" and "Set of specifications # 2 (ETCS baseline 3 and GSM-R baseline 0)". In the decision of May 2016 there are three tables: "Set of specifications # 1 (ETCS Baseline 2 and GSM-R Baseline 1)", "Set of specifications # 2 (ETCS Baseline 3 Maintenance Release 1 and GSM-R Baseline 1)", and "Set of specifications # 3 (ETCS Baseline 3 Release 2 and GSM-R Baseline 1)". In that decision the SRS (System Requirement Specification) and DMI (ETCS Driver Machine Interface) are kept at 3.4.0 for Set 2 while updating Set 3 to SRS and DMI 3.6.0. All three of the tables (Set 1, Set 2 and Set 3) are updated to include the latest EIRENE FRS 8.0.0 including the same GSM-R SRS 16.0.0 to ensure interoperability. In that decision the SRS is kept at 2.3.0 for Set 1 – and the decision of 2012/88/EU was repealed that was first introducing the interoperability of Set 1 and Set 2 (with SRS 3.3.0 at the time) based on GSM-R Baseline 0. Introduction of Baseline 3 on railways require installation of it on board, which require re-certification of trains. This will cost less than first ETCS certification, but still around €100k per vehicle. The first live tests of Baseline 3 took place in Denmark July 2016. Denmark wants to install ERTMS on all its railways, and then use Baseline 3. British freight and passenger operators have signed contracts to install Baseline 3 in their trains, the first around 2020. The development of ETCS has matured to a point that cross-border traffic is possible and some countries have announced a date for the end of older systems. The first contract to run the full length of a cross-border railway was signed by Germany and France in 2004 on the high-speed line from Paris to Frankfurt, including LGV Est. The connection opened in 2007 using ICE3MF, to be operational with ETCS trains by 2016. The Netherlands, Germany, Switzerland and Italy have a commitment to open Corridor A from Rotterdam to Genoa for freight by the start of 2015. Non-European countries also are starting to deploy ERTMS/ETCS, including Algeria, China, India, Israel, Kazakhstan, Korea, Mexico, New Zealand, and Saudi Arabia. The European Commission has mandated that European railways to publish their deployment planning up to 5 July 2017. This will be used to create a geographical and technical database (TENtec) that can show the ETCS deployment status on the Trans-European Network. From the comparative overview the commission wants to identify the needs for additional coordination measures to support the implementation. Synchronous with the publication of ETCS SRS 3.6.0 on 15 June 2017 the Regulation 2016/796/EC was published. It mandates the replacement of the European Railways Agency by the European Union Agency for Railways. The agency was tasked with the creation of a regulatory framework for a Single European Railway Area (SERA) in the 4th Railway Package to be resolved in late June 2016. The costs for the switch to ETCS are well documented in the Swiss reports from their railway operator SBB to the railway authority BAV. In December 2016 it was shown that they could start switching parts of the system to ETCS Level 2 whenever a section needs improvement. This would not only result in a network where sections of ETCS and the older ZUB would switch back and forth along lines, but the full transition to ETCS would last until 2060 and its cost were estimated at 9.5 billion Swiss Franc (US$ 9.69 billion). The expected advantages of ETCS for more security and up to 30% more throughput would also be at stake. Thus legislation favours the second option where the internal equipment of interlocking stations would be replaced by new electronic ETCS desks before switching the network to ETCS Level 2. However the current railway equipment manufacturers did not provide enough technology options at the time of the report to start it off. So the plan would be to run feasibility studies until 2019 with a projected start of changeover set to 2025. A rough estimate indicates that the switch to ETCS Level 2 could be completed within 13 years from that point and it would cost about 6.1 billion Swiss Franc (US$ 6.22 billion). For comparison, SBB indicated that the maintenance of lineside signals would also cost about 6.5 billion Swiss Franc (US$ 6.63 billion) which however can be razed once Level 2 is effective. The Swiss findings influenced the German project "Digitale Schiene" (digital rail). It is estimated that 80% of the rail network can be operated by GSM-R without lineside signals. This will bring about 20% more trains that can be operated in the country. The project was unveiled in January 2018 and it will start off with a feasibility study on electronic interlocking stations that should show a transition plan by mid 2018. It is expected that 80% of the network have been rebuilt to the radio-controlled system by 2030. This is more extensive than earlier plans which focused more on ETCS Level 1 with Limited Supervision instead of Level 2. The ETCS standard has listed a number of older Automatic Train Controls (ATC) as Class B systems. While they are set to obsolescence, the older line side signal information can be read by using Specific Transmission Modules (STM) hardware and fed the Class B signal information to a new ETCS onboard safety control system for partial supervision. In practice an alternative transition scheme is used where an older ATC is rebased to use Eurobalises. This leverages the fact that a Eurobalise can transmit multiple information packets and the reserved national datagram (packet number 44) can encode the signal values from the old system in parallel with ETCS datagram packets. The older train-born ATC system is equipped with an additional Eurobalise reader that converts the datagram signals. This allows for a longer transitional period where the old ATC and Eurobalises are attached on the sleepers until all trains have a Eurobalise reader. The newer ETCS-compliant trains can be switched to an ETCS operation scheme by a software update of the onboard train computer. In Switzerland a replacement of the older Integra-Signum magnets and ZUB 121 magnets to Eurobalises in the Euro-Signum plus Euro ZUB operation scheme is under way. All trains had been equipped with Eurobalise readers and signal converters until 2005 (generally called "Rucksack" " In Belgium the TBL 1 crocodiles were complemented with Eurobalises in the TBL 1 operation scheme. The TBL 1 definition allowed for an additional speed restriction to be transmitted to the train computer already. Likewise in Luxembourg the Memor II (using crocodiles) was extended into a Memor II operation scheme. In Berlin the old mechanical train stops on the local S-Bahn rapid transit system are replaced by Eurobalises in the newer ZBS train control system. Unlike the other systems it is not meant to be transitional for a later ETCS operation scheme. The signalling centres and the train computer use ETCS components with a specific software version, manufacturers like Siemens point out that their ETCS systems can be switched for operating on ETCS, TBL, or ZBS lines. The Wuppertal Suspension Railway called for bids on a modernization of its train protection and management system. Alstom won the tender with a plan largely composed of ETCS components. Instead of GSM-R the system uses TETRA which had been in use already for voice communication. The TETRA system will be expanded to allow movement authority being signaled by digital radio. Because train integrity will not be checked, the solution was called as ETCS Level 2 by the manufacturer. The usage of moving blocks was dropped however while the system was implemented with just 256 balises checking the odometry of the trains that signal their position by radio to the ETCS control center. It is expected that headways will drop from 3,5 minutes to 2 minutes when the system is activated. ETCS is specified at four numbered levels: Level 0 applies when an ETCS-fitted vehicle is used on a non-ETCS route. The trainborne equipment monitors the maximum speed of that type of train. Since signals can have different meanings on different railways, this level places additional requirements on drivers' training. If the train has left a higher-level ETCS, it might be limited in speed globally by the last balises encountered. Level 1 is a cab signalling system that can be superimposed on the existing signalling system, leaving the fixed signalling system (national signalling and track-release system) in place. Eurobalise radio beacons pick up signal aspects from the trackside signals via signal adapters and telegram coders (Lineside Electronics Unit – LEU) and transmit them to the vehicle as a movement authority together with route data at fixed points. The on-board computer continuously monitors and calculates the maximum speed and the braking curve from these data. Because of the spot transmission of data, the train must travel over the Eurobalise beacon to obtain the next movement authority. In order for a stopped train to be able to move (when the train is not stopped exactly over a balise), there are optical signals that show permission to proceed. With the installation of additional Eurobalises ("infill balises") or a Euro Loop between the distant signal and main signal, the new proceed aspect is transmitted continuously. The Euro Loop is an extension of the Eurobalise over a particular distance that basically allows data to be transmitted continuously to the vehicle over cables emitting electromagnetic waves. For example, in Norway and Sweden the meanings of single green and double green are contradictory. Drivers have to know the difference (already with traditional systems) to drive beyond the national borders safely. In Sweden, the ETCS Level 1 list of signal aspects are not fully included in the traditional list, so there is a special marking saying that such signals have slightly different meanings. Whereas ETCS L1 Full Supervision requires supervision to be provided at every signal, ETCS L1 Limited Supervision allows for only a part of the signals to be included, thus allowing to tailor the installation of equipment, only to points of the network where the increase in functionality justifies the costs. Formally, this is possible for all ETCS levels, but it is currently only applied with Level 1. As supervision is not provided at every signal, this implies that cab signalling is not available and the driver must still look out for trackside signals. For this reason, the level of safety is not as high, as not all signals are included and there is still reliance on the driver seeing and respecting the trackside signalling.. Cost advantages come from reduced efforts necessary for callibrating, configurating and designing the track equippment and ETCS telegramms. Another advantage is, that Limited Supervision has little requirements for the underlying interlocking, hence it can be applied even on lines with mechanical interlockings as long as LEUs can read respective signal aspects. In contrast Level 2 requires to replace older interlockings with electronic or digital interlockings. That has led to railway operators pushing for the inclusion of Limited Supervision into the ETCS Baseline 3. Although interoperable according to TSI, implementations of Limited Supervision are much more diverse than other ECTS modes, e.g. functionality of L1LS in Germany is strongly based on PZB principles of operation and common signal distances. Limited Supervision mode was proposed by RFF/SNCF (France) based on a proposal by SBB (Switzerland). Several years later a steering group was announced in spring 2004. After the UIC workshop on 30 June 2004 it was agreed that UIC should produce a FRS document as the first step. The resulting proposal was distributed to the eight administrations that were identified: ÖBB (Austria), SNCB/NMBS (Belgium), BDK (Denmark), DB Netze (Germany), RFI (Italy), CFR (Romania), Network Rail (UK) and SBB (Switzerland). After 2004 German Deutsche Bahn took over the responsibility for the change request. In Switzerland the Federal Office of Transport (BAV) announced in August 2011 that beginning with 2018 the Eurobalise-based Euro ZUB/Euro Signum signalling will be switched to Level 1 Limited Supervision. The north-south corridor should be switched to ETCS by 2015 according to international contracts regarding the TEN-T Corridor-A from Rotterdam to Genova (European backbone). Movement authority and other signal aspects are displayed in the cab for the driver. Apart from a few indicator panels, it is therefore possible to dispense with trackside signalling. However, the train detection and the train integrity supervision still remain in place at the trackside. Train movements are monitored continually by the radio block centre using this trackside-derived information. The movement authority is transmitted to the vehicle continuously via GSM-R or GPRS together with speed information and route data. The Eurobalises are used at this level as passive positioning beacons or "electronic milestones". Between two positioning beacons, the train determines its position via sensors (axle transducers, accelerometer and radar). The positioning beacons are used in this case as reference points for correcting distance measurement errors. The on-board computer continuously monitors the transferred data and the maximum permissible speed. With Level 3, ETCS goes beyond pure train protection functionality with the implementation of full radio-based train spacing. Fixed train detection devices (GFM) are no longer required. As with Level 2, trains find their position themselves by means of positioning beacons and via sensors (axle transducers, accelerometer and radar) and must also be capable of determining train integrity on board to the very highest degree of reliability. By transmitting the positioning signal to the radio block centre, it is always possible to determine that point on the route the train has safely cleared. The following train can already be granted another movement authority up to this point. The route is thus no longer cleared in fixed track sections. In this respect, Level 3 departs from classic operation with fixed intervals: given sufficiently short positioning intervals, continuous line-clear authorisation is achieved and train headways come close to the principle of operation with absolute braking distance spacing ("moving block"). Level 3 uses radio to pass movement authorities to the train. Level 3 uses train reported position and integrity to determine if it is safe to issue the movement authority. Solutions for reliable train integrity supervision are highly complex and are hardly suitable for transfer to older models of freight rolling stock. The Confirmed Safe Rear End (CSRE) is the point in rear of the train at the furthest extent of the safety margin. If the Safety margin is zero, the CSRE aligns with the Confirmed Rear End. Some kind of end-of-train device is needed or special lines for rolling stock with included integrity checks like commuter multiple units or high speed passenger trains. A ghost train is a vehicle in the Level 3 Area that are not known to the Level 3 Track-side. A variant of Level 3 is ERTMS Regional, which has the option to be used with virtual fixed blocks or with true moving block signalling. It was early defined and implemented in a cost sensitive environment in Sweden. In 2016 with SRS 3.5 it was adopted by core standards and is now officially part of Baseline 3 Level 3. It is possible to use train integrity supervision, or by accepting limited speed and traffic volume to lessen the effect and probability of colliding with detached rail vehicles. ERTMS Regional has lower commissioning and maintenance costs, since trackside train detection devices are not routinely used, and is suitable for lines with low traffic volume. These low-density lines usually have no automatic train protection system today, and thus will benefit from the added safety. Instead of using fixed balises to detect train location there may be "virtual balises" based on satellite navigation and GNSS augmentation. Several studies about the usage of GNSS in railway signalling solutions have been researched by the UIC (GADEROS/GEORAIL) and ESA (RUNE/INTEGRAIL). Experiences in the LOCOPROL project show that real balises are still required in railway stations, junctions, and other areas where greater positional accuracy is required. The successful usage of satellite navigation in the GLONASS-based Russian ABTC-M block control has triggered the creation of the ITARUS-ATC system that integrates Level 2 RBC elements – the manufacturers Ansaldo STS and VNIIAS in which a SIL-4 train localisation at signalling system level has been developed using differential GPS. There is a pilot project "ERSAT EAV" running since 2015 with the objective to verify the suitability of EGNSS as the enabler of cost-efficient and economically sustainable ERTMS signalling solutions for safety railway applications. whose main scope is to specify ETCS virtual balise functionality, taking into account the interoperability requirement. Following the NGTC specifications the future interoperable GNSS positioning systems, supplied by different manufacturers, will reach the defined positioning performance in the locations of the virtual balises. All the trains compliant with ETCS will be fitted with on-board systems certified by Notified Bodies. This equipment consists of wireless communication, rail path sensing, central logic unit, cab displays and control devices for driver action. The Man Machine Interface (MMI) is the standardised interface for the driver, also called "Driver Machine Interface" (DMI). It consists of a set of colour displays with touch input for ETCS and separate for GSM-R communication. This is added with control devices specific for the train type. The Specific Transmission Module (STM) is a special interface for the EVC for communicating with legacy Class B ATP systems like PZB, Memor and ATB. It consists of specific sensing elements to lineside installations and an interface for hardware and logic adapting interface to EVC. The EVC must get special software for translation of legacy signals to unified internal ETCS communication. The driver is using standard ETCS cab equipment also on non ETCS lines. The STM enables therefore the usage of the ETCS equipped driving vehicle on the non-equipped network and is today essential for interoperability. The odometric sensors are significant for exact position determination. In ETCS Level 2 installations are rare installation of eurobalises as definite milestones. Between such milestones the position is estimated and measured relative to the last passed milestone. Initially it was tested, that in difficult adhesive conditions axle revolution transmitters would not give required precision. The European Vital Computer (EVC) also called Eurocab is the heart of local computing capabilities in the driving vehicle. It is connected with external data communication, internal controls to speed regulation of the loco, location sensors and all cab devices of the driver. The Euroradio communication unit is compulsory and is used for voice and data communication. Because in ETCS Level 2 all signalling information is exchanged via GSM-R, the equipment is fully doubled with two simultaneous connections to the RBC. The Juridical Recording Unit (JRU) is part of the EVC for recording the last actions of the driver, last parameters of signalling and machine conditions. Such a train event recorder is functionally equivalent to the flight recorder of aircraft. The Train Interface Unit (TIU) is the interface of the EVC to the train and/or the locomotive for submitting commands or receiving information. Lineside equipment is the fixed installed part of ETCS installation. According to ETCS Levels the rail related part of installation is decreasing. While in Level 1 sequences with two or more of eurobalises are needed for signal exchange, in Level 2 balises are used for milestone application only. It is replaced in Level 2 by mobile communication and more sophisticated software. In 2017 first positive tests for satellite positioning were done. The Eurobalise is a passive or active antenna device mounted on rail sleepers. Mostly it transmits information to the driving vehicle. It can be arranged in groups to transfer information. Transparent Data Balises are sending changing information from LEU to the trains, e.g. Fixed Balises are programmed for a special information like gradients and speed restrictions. The Euroloop is an extension for Eurobalises in ETCS Level 1. It is a special Leaky feeder for transmitting information telegrams to the car. The Lineside Electronic Unit (LEU) is the connecting unit between the Transparent Data Balises with signals or Signalling control in ETCS Level 1. A Radio Block Centre is a specialised computing device with specification Safety integrity level 4 (SIL) for generating Movement Authorities (MA) and transmitting it to trains. It gets information from Signalling control and from the trains in its section. It hosts the specific geographic data of the railway section and receives cryptographic keys from trains passing in. According to conditions the RBC will attend the trains with MA until leaving the section. RBC have defined interfaces to trains, but have no regulated interfaces to Signalling Control and only have national regulation. To be a reference laboratory ERA is requesting the laboratories to be accredited ISO17025. GSM is no longer being developed outside of GSM-R, the manufacturers have committed to supplying GSM-R till at least 2030. The ERA is considering what action is needed to smoothly transition to a successor system such as GPRS or Edge. Corridor A has two routes in Germany – the double track east of the Rhine (rechte Rheinstrecke) will be ready with ETCS in 2018 (Emmerich, Oberhausen, Duisburg, Düsseldorf, Köln-Kalk, Neuwied, Oberlahnstein, Wiesbaden, Darmstadt, Mannheim, Schwetzingen, Karlsruhe, Offenburg, Basel), while the upgrade of the double track west of the Rhine (linke Rheinstrecke) will be postponed. Corridor F will be developed in accordance with Poland as far as it offers ETCS transport: Frankfurt – Berlin – Magdeburg will be ready in 2012, Hanover to Magdeburg – Wittenberg – Görlitz in 2015. At the other end Aachen to Oberhausen will be ready in 2012, the missing section from Oberhausen to Hanover in 2020. The other two corridors are postponed and Germany chooses to support the equipment of locomotives with STMs to fulfill the requirement of ETCS transport on the corridors. In Belgium the state railway company SNCB (in French, in Dutch NMBS, in German NGBE) led all activities for introduction of ETCS since the end of the 1990s. The interest resulted from new High Speed Lines (HSL) under construction, the development of the ports at the Atlantic and technically rotting national signalling systems. in 1999 the council of SNCB decided the opening of HSL 2 with proprietary system TBL 2, but all following lines should use ETCS. To rise the level of security on conventional lines, it was thought to use ETCS L1 for compatibility. But because of high costs for full implementation on rolling stock, it was chosen to select standard components from ETCS for interfacing locos (receiver) and rails (balises) to easy support existing infrastructure. The balises were sending information with reserved national paket type 44, compatible with common signalling. Later it can be complemented with standardised ETCS information. This is the same migration path as chosen in Italy (SCMT) or Switzerland (Euro-Signum and Euro-ZUB). In 2003 the SNCB selected a consortium to supply ETCS for the next high-speed lines with Level 2 and fallback with Level 1. It was chosen to supply ETCS L1LS first and later migrate to L1FS. So it was started tendering the renewing of 4000 signals with TBL1 and L1 including support for 20 years in 2001. Following the privatisation of SNCB in 2006 a split-off company Infrabel stepped in to be responsible for the whole state railway infrastructure. It continued the introduction of ETCS railway infrastructure, whereas SNCB was responsible for rolling material. Halle train collision) caused by missing or malfunctioning protection systems, there was the obvious target to raise the security level in the whole network. The first line in ETCS operation was HSL 3 in 2007, which is 56 km (35 mi) long. Because of lack of trains equipped with ETCS, the commercial start of operations was in 2009 with ICE 3 and Thalys trains. The operations started with ETCS SRS 2.2.2 and were later upgraded to 2.3.0. The HSL 4 high-speed line was constructed at the same time as HSL 3 and so got the same ETCS equipment. Testing began in 2006 and commercial traffic started about 2008 with locomotive-hauled trains under Level 1. In 2009 commercial high-speed traffic started under ETCS L2 with supported Thalys- and ICE-trains like on HSL 3. A special feature is the first full-speed gapless border crossing under ETCS L2 supervision with HSL Zuid. Infrabel has budgeted about 332 Million Euro for signalling including ETCS in 2015. After tendering it was given in summer 2015 a long time order to the consortium of Siemens Mobility and Cofely-Fabricom about the installation of ETCS L2 on more than 2200 km of rails. The order includes the delivery of computer based interlockings for the full network until 2025. The complete Belgian part of the European north-south Corridor C (port of Antwerp–Mediterranean Sea) with a length of about 430 km is crossable with ETCS L1 since the end of 2015. According to Infrabel was this the longest conventional railway supported with ETCS in Europe. The first project that was intended to implement ETCS was the Köln–Frankfurt high-speed rail line that had been under construction since 1995. Due to the delays in the ETCS specification a new variant of LZB (CIR ELKE-II) was implemented instead. The next planned and first actual implementation was on the Leipzig-Ludwigsfelde main line to Berlin. There, SRS 2.2.2 was tested together with a PZB and LZB mixed installation in conditions of fast and mixed traffic. The section was co-financed by the EU and DB to gain more experience with the ETCS Level 2 mode. Since April 2002 the ETCS section was in daily usage and in March 2003 it was announced that it had reached the same degree of reliability as before using ETCS. December 2005 an ETCS train ran at 200 km/h as a part of the normal operation plan on the line north of Leipzig to obtain long-term recordings. As of 2009, the line had been decommissioned for ETCS and is henceforth in use with LZB and PZB. The ETCS equipment seems partly not to be upgradable. In 2011, the installation of ETCS L2 (SRS 2.3.0d) was ordered for 14 Mio EUR following the reconstruction and enhancement of the railway line Berlin-Rostock. The newly built Ebensfeld–Erfurt segment of Nuremberg–Erfurt high-speed railway as well as the Erfurt–Leipzig/Halle high-speed railway and the upgraded Erfurt–Eisenach segment of the Halle–Bebra railway are equipped with ETCS L2. The north-eastern part (Erfurt–Leipzig/Halle) is in commercial use since December 2015 exclusively with ETCS L2 SRS 2.3.0d. The southern part (Ebensfeld–Erfurt) started test running and driver training in the end of August 2017 ECTS on the western part (Erfurt–Eisenach) was also scheduled for commencing operation in December 2017 but commission was delayed until August 2018. Germany will start replacing all its PZB and LZB systems in 2015, to be finished by 2027. During 2014 it was planned to use a dual equipment for the four main freight corridors to comply with the EC 913/2010 regulation. Further testing showed that a full ETCS system can increase capacity by 5-10% leading into a new concept "Zukunft Bahn" to accelerate the deployment, presented in December 2015. In a first step, another 1750 km of existing railway lines are planned to be equipped with ETCS until 2023, focusing on the Rhine-Alpine corridor, the Paris–Southwest Germany corridor and border-crossing lines. In January 2018 the project "Digitale Schiene" (digital rail) was unveiled that intended to bring about a transition plan by mid 2018. Deutsche Bahn intends to equip 80% of the rail network with GSM-R by 2030 razing any lineside signals in the process. This will bring about 20% more trains that can be operated in the country. The Digital Rail project came about shortly after the Nuremberg–Erfurt high-speed railway was operational in December 2017 being the first high-speed line to have no lineside signals anymore. After some teething problems with radio reception it settled within the expected range of usability. Priority is on the 1450 km Rhine Corridor that is about to be equipped with ETCS Level 2. Switzerland is expecting an increase in capacity of 30% that will probably come out the same on congested sections along the Rhine. New high speed line Athens to Thessaloniki will be the first ETCS Level 1 in Greece. System expected to be ready by the end of 2021 In Hungary, the Zalacséb–Hodoš line was equipped with Level 1 as a pilot project in 2006. The Budapest–Hegyeshalom Level 1 was launched in 2008, and it was extended to Rajka (GYSEV) in 2015. The Békéscsaba-Lőkösháza line was equipped with Level 1 as an extension of the Level 2 network until further refurbishments will take place. In Hungary Level 2 is under construction in the Kelenföld-Székesfehérvár line as a part of a full reconstruction, and planned to be ready before 2015. In Hungary Level 2 is under construction, but due to problems with the installation of GSM-R, all of them are delayed. The Level 2 system is under constructuion in several phases. Currently the Boba-Hodoš, Székesfehérvár station, Székesfehérvár-Ferencváros, Ferencváros-Monor, Monor-Szajol, Szajol-Gyoma and the Gyoma-Békéscsaba sections are under construction. The GYSEV is currently installing Level 2 to the Sopron-Szombathely-Szentgotthárd line. National Capital Region Transport Corporation has decided to equip European Train Control System (ETCS) on its Sarai Kale Khan hub in India's First Rapid Rail corridor-Delhi Meerut RRTS Route. In Israel ETCS Level 2 will begin replacing PZB in 2020. Three separate tenders were issued in 2016 for this purpose (one contract each was let for track-side infrastructure, rolling-stock integration, and the erection of a GSM-R network). Concurrent with the implementation of ERTMS are railway electrification works, and an upgrade of the signaling system in the northen portion of Israel Railways' network from relay-based to electronic interlocking. (The southern portion of the network already employs electronic signaling.) In Libya, Ansaldo STS was awarded a contract in July 2009 to install Level 2. Procurement for ETCS started in 1999 and the tender was won by Alcatel SEL in July 2002. March 2005 a small network had been established that was run under ETCS Level 1. The track-side installations were completedin 2014 after spending about 33 Million Euro. The equipment of the rolling stock did take a bit longer. In early 2016 it became known that the new Class 2200 could not run on Belgium lines. In February 2017 the changeover of Class 3000 was not even started, and Class 4000 had just one prototype installation. However the problems were resolved later with the complete rolling stock having ETCS installations by December 2017. January 2018 all trains have to use ETCS by default and it should be continued to use on tracks in Belgium and France as far as possible. The government had pushed for the changeover following the rail accident of Bettembourg on 14. With the rolling stock being ready as well, the end date of the usage of the old Memor-II -systems was set to 31. ETCS equips and will equip the high-speed lines that link Tangier to Kénitra (in service from 2018) and Kénitra to Casablanca via Rabat (under construction, planned to open in 2020). Other high-speed lines planned to link Casablanca to Agadir and Rabat to Oujda from 2030 will likely be equipped as well. In August 2015 the eastern branch of the Østfold Line becomes first line with ETCS functionality in Norway. Level 1 is currently being installed in the Manila LRT Line 1 in preparation for the Cavite extension of the line. In Poland, Level 1 was installed in 2011 on the CMK high-speed line between Warsaw and Katowice-Kraków, to allow speeds to be raised from 160 km/h (99 mph) to 200 km/h (124 mph), and eventually to 250 km/h (155 mph). The CMK line, which was built in the 1970s, was designed for a top speed of 250 km/h, but was not operated above 160 km/h due to lack of cab signalling. The ETCS signalling on the CMK was certified on 21 November 2013, In Poland, Level 2 has been installed as part of a major upgrading of the 346 km Warsaw-Gdańsk-Gdynia line that reduced Warsaw – Gdańsk travel times from five to two hours and 39 minutes in December 2015. In Slovakia, the system has been deployed as part of the Bratislava–Košice mainline modernisation program, currently between Bratislava (east of Bratislava-Rača station) and Nové Mesto nad Váhom, with the rest of the line to follow. The current implementation is limited to 160 km/h due to limited braking distances between the control segments. ETCS Level 1 will also be installed in mainlines extended from Bangkok to Chumphon (Southern Line), Nakhon Sawan (Northern Line), Khon Kaen (Northeastern Line), Si Racha (Eastern Coast Line) and in shortcut line from Chachoengsao to Kaeng Khoi (Shortcut from Eastern Line to North/Northeastern Line) along with Double Tracking Phase I projects and ATP system upgrade of existing double track lines, both scheduled to be completed in 2022. Rbc baseline rbc st eustache With RBC Online Banking you'll have access to the tools and services that give you more control over your money and save time. RBC Mobile. Royal Bank of Canada FREE - On Google Play. RBC Royal Bank in 1330 Baseline Rd, 1330 Baseline Rd, Nepean, ON, K2C 0A9, Store Hours, Phone number, Map, Latenight, Sunday hours, Address, Banks This file presents a baseline RBC model with TFP and government spending shocks, calibrated to US data from * 1947Q16Q1. The model setup is described in Handout_RBC_and resembles the one in King/Rebelo 1999 * Resuscitating Real Business Cycles, Handbook of Macroeconomics, Volume 1 and Initial results from phase 2 study evaluating an investigational use of luspatercept-aamt in myelofibrosis-associated anemia showed promising clinical activity – companies plan to initiate pivotal, phase 3 study called INDEPENDENCE in 2020 Longer-term follow-up from pivotal phase 3 studies of MEDALIST in MDS-associated anemia and BELIEVE in beta thalassemia-associated anemia showed patients experiencing sustained clinical benefit PRINCETON, N. & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE: BMY) and Acceleron Pharma (NASDAQ: XLRN) today announced data evaluating the erythroid maturation agent (EMA) Reblozyl (luspatercept-aamt) in patients with anemia associated with a range of serious and rare blood diseases were presented at the 2019 ASH Annual Meeting in Orlando, Fla. Data from investigational uses of luspatercept-aamt included the initial results from a phase 2 study in myelofibrosis-associated anemia. Presentations also included updated results from two pivotal phase 3 studies presented at last year’s ASH meeting—the MEDALIST study in adult patients with anemia associated with very low-, low- and intermediate-risk myelodysplastic syndromes (MDS) who have ring sideroblasts and require red blood cell (RBC) transfusions, and the BELIEVE study in adult patients with anemia associated with beta thalassemia who require regular RBC transfusions. “The data presented at ASH this year underscore the role that Reblozyl, the first and only erythroid maturation agent, plays for patients with beta thalassemia-associated anemia and may serve in further investigational uses in myelofibrosis and MDS,” said Samit Hirawat, M. “We’re encouraged to see positive study results from luspatercept-aamt in patients with myelofibrosis-associated anemia, including among those receiving concomitant ruxolitinib, as JAK inhibitors are a mainstay of myelofibrosis symptomatology management,” said Habib Dable, President and Chief Executive Officer of Acceleron. “This development, coupled with updated data showing continued clinical benefit from luspatercept-aamt treatment in patients with MDS and beta thalassemia, underscores our confidence in luspatercept-aamt’s potential to address significant unmet needs among patients with a range of chronic anemias.” Seventy-six patients were enrolled in the phase 2 study in multiple cohorts of patients including two groups with anemia only (hemoglobin level equal to or below 9.5 grams per deciliter (g/d L) in a 12-week period prior to the first dose) and without concomitant ruxolitinib (Cohort 1; n=22) or with concomitant ruxolitinib (Cohort 3A; n=14). Two other groups included transfusion dependent (TD; received 2-4 RBC units per 28 days in the 12 weeks prior to the date of the first dose) patients without concomitant ruxolitinib (Cohort 2; n=21) and with concomitant ruxolitinib (Cohort 3B n=19). Patients in Cohort 3A or 3B were required to be on a stable dose of ruxolitinib for at least 16 weeks prior to initiating luspatercept-aamt. All patients received luspatercept-aamt at a starting dose of 1 mg/kg subcutaneously in three-week treatment cycles and dose increases were allowed up to a maximum dose level of 1.75 mg/kg. For anemia-only patients (Cohorts 1 and 3A), the primary endpoint was a hemoglobin (Hb) increase of at least 1.5 g/d L from baseline for at least 12 consecutive weeks at every assessment within the first 24 weeks on the study, in the absence of any RBC transfusions. An additional endpoint was the proportion of patients achieving a mean Hb increase of at least 1.5 g/d L over any consecutive 12-week period in absence of RBC transfusions. As of the clinical data cutoff (August 5, 2019), 14% (3/22) and 21% (3/14) of anemia-only patients met the primary endpoint in Cohorts 1 and 3A, respectively. Additionally, 18% (4/22) of Cohort 1 and 64% (9/14) of Cohort 3A patients achieved a mean Hb increase of at least 1.5 g/d L from baseline over any consecutive 12-week period. For patients receiving RBC transfusions (Cohorts 2 and 3B), the primary endpoint was RBC transfusion independence (RBC-TI) for at least 12 consecutive weeks within the first 24 weeks of the study. An additional endpoint was the proportion of patients demonstrating at least a 50% reduction in their transfusion burden from baseline (minimum 4 RBC units) over at least any consecutive 12-week period. In Cohorts 2 and 3B, 10% (2/21) and 32% (6/19) of patients achieved the primary endpoint, respectively. Additionally, 38% (8/21) of Cohort 2 and 53% (10/19) of Cohort 3B patients achieved at least a 50% reduction in RBC transfusion burden from baseline (minimum 4 RBC units). Four percent (3/76) of patients had grade 3 or higher treatment-emergent adverse events (TEAEs). The most commonly occurring TEAEs of any grade greater than 3% were hypertension (12%), bone pain (9%) and diarrhea (5%). Treatment discontinuations as the result of TEAEs occurred in seven (9%) patients. As a result of the phase 2 study, Bristol-Myers Squibb and Acceleron plan to move forward with the pivotal phase 3 INDEPENDENCE study in patients with myelofibrosis-associated anemia who are being treated with JAK inhibitor therapy and who require RBC transfusions. In an assessment of efficacy and safety, updated results from the pivotal phase 3 MEDALIST study of an investigational use of luspatercept-aamt in patients with IPSS-R very low-, low- or intermediate-risk MDS with ring sideroblasts who require regular RBC transfusions were presented. In the study, 229 patients were randomized 2:1 with 153 patients receiving luspatercept-aamt. This updated analysis measured the achievement and number of individual periods of RBC-TI of at least 8 weeks throughout the course of the study. Additionally, clinical benefit (RBC-TI) of at least 8 weeks and/or modified hematologic improvement-erythroid (HI-E) was also assessed, along with the total duration of the clinical benefit, which was defined as time from achieving clinical benefit until discontinuation due to loss of benefit, adverse events or other causes. In the analysis, the median baseline RBC transfusion burden for both the luspatercept-aamt and placebo arms was 5 units per 8 weeks. As of the clinical cutoff (July 1, 2019), 47.7% (73/153) of luspatercept-aamt patients and 15.8% (12/76) of placebo patients achieved at least one episode of RBC-TI lasting at least 8 weeks at any point in the study. Sixty-nine point nine percent (51/73) of patients who responded to luspatercept-aamt experienced multiple episodes of at least 8 weeks of RBC-TI at any point, interceded by occasional transfusions. The median total duration of clinical benefit was 92.3 weeks for luspatercept-aamt responders (n=98) and 26.8 weeks for placebo (n=20), with 26.8% of luspatercept-aamt-treated patients remaining on treatment. The median treatment duration for all RBC-TI responders was 109.1 weeks for luspatercept-aamt-treated patients and 53.6 weeks for patients on placebo. Adverse events (AEs) occurring more frequently with luspatercept-aamt compared to placebo were fatigue, asthenia and headache. These occurred during cycles 1-4 and were mainly grade 1 or 2, with the incidence decreasing over time. Progression to acute myeloid leukemia was similar between the luspatercept-aamt (2%) and placebo (2.6%) arms. The companies also presented an updated analysis of the pivotal phase 3 BELIEVE study evaluating luspatercept-aamt in adult patients with beta thalassemia who require regular RBC transfusions. In the study, 336 patients were randomized 2:1, with 224 patients receiving luspatercept-aamt. As of the clinical cutoff (January 7 2019), 45.1% (101/224) of luspatercept-aamt patients and 2.7% (3/112) of placebo patients had achieved at least a 33% reduction in RBC transfusion burden over any 24-week period. Among the luspatercept-aamt patients who had a response, 73.3% (74/101) had at least 2 separate responses, with 59.4% (60/101) having 3 or more responses. These AEs typically occurred early on, and incidence decreased over time. The median duration of clinical benefit (defined as the time from first response of at least a 33% reduction in RBC transfusion over any 24-week interval to discontinuation due to any cause) for patients who responded to luspatercept-aamt was 76.3 weeks (24-128.1). The Food and Drug Administration has recently granted approval of Reblozyl for the treatment of anemia in adult patients with beta thalassemia who require regular RBC transfusions. The most commonly observed AEs in the safety population (n=332) included in luspatercept-aamt and placebo patients, respectively, bone pain (20.2% vs. Reblozyl is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia. Reblozyl is currently being reviewed by the FDA for an indication in patients with MDS, and the agency has set a Prescription Drug User Fee Act (PDUFA), or target action, date of April 4, 2020 for completion of the review. Reblozyl is not approved for use in patients with MDS or myelofibrosis in any country. At Bristol-Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase quality, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients. Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational chimeric antigen receptor (CAR) T-cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients. About Reblozyl (luspatercept-aamt) Reblozyl is an erythroid maturation agent (EMA) that promoted late-stage red blood cell maturation in animal models. for the treatment of anemia in adult patients with beta thalassemia who require regular RBC transfusions. Bristol-Myers Squibb and Acceleron are jointly developing Reblozyl as part of a global collaboration. Reblozyl is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia. A phase 3 trial (COMMANDS) in erythroid-stimulating agent-naïve, lower-risk MDS patients, the BEYOND phase 2 trial in adult patients with non-transfusion-dependent beta thalassemia, and a phase 2 trial in myelofibrosis patients are ongoing. REBLOZYL is indicated for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions. REBLOZYL is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia. Important Safety Information WARNINGS AND PRECAUTIONS Thrombosis/Thromboembolism Thromboembolic events (TEE) were reported in 8/223 (3.6%) REBLOZYL-treated patients. TEEs included deep vein thrombosis, pulmonary embolus, portal vein thrombosis, and ischemic stroke. Patients with known risk factors for thromboembolism (splenectomy or concomitant use of hormone replacement therapy) may be at further increased risk of thromboembolic conditions. Consider thromboprophylaxis in patients at increased risk of TEE. Monitor patients for signs and symptoms of thromboembolic events and institute treatment promptly. Hypertension Hypertension was reported in 10.7% (61/571) of REBLOZYL-treated patients. Across clinical studies, the incidence of Grade 3 to 4 hypertension ranged from 1.8% to 8.6%. In patients with beta thalassemia with normal baseline blood pressure, 13 (6.2%) patients developed systolic blood pressure (SBP) 80 mm Hg. Monitor blood pressure prior to each administration. Manage new or exacerbations of preexisting hypertension using anti-hypertensive agents. Embryo-Fetal Toxicity REBLOZYL may cause fetal harm when administered to a pregnant woman. REBLOZYL caused increased post-implantation loss, decreased litter size, and an increased incidence of skeletal variations in pregnant rat and rabbit studies. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 3 months after the last dose. ADVERSE REACTIONS Serious adverse reactions occurring in 1% of patients included cerebrovascular accident and deep vein thrombosis. A fatal adverse reaction occurred in 1 patient treated with REBLOZYL who died due to an unconfirmed case of acute myeloid leukemia (AML). Most common adverse reactions (at least 10% for REBLOZYL and 1% more than placebo) were headache (26% vs 24%), bone pain (20% vs 8%), arthralgia (19% vs 12%), fatigue (14% vs 13%), cough (14% vs 11%), abdominal pain (14% vs 12%), diarrhea (12% vs 10%) and dizziness (11% vs 5%). LACTATION It is not known whether REBLOZYL is excreted into human milk or absorbed systemically after ingestion by a nursing infant. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because many drugs are excreted in human milk, and because of the unknown effects of REBLOZYL in infants, a decision should be made whether to discontinue nursing or to discontinue treatment. Because of the potential for serious adverse reactions in the breastfed child, breastfeeding is not recommended during treatment and for 3 months after the last dose. Please see full Prescribing Information for REBLOZYL. Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at or follow us on Linked In, Twitter, You Tube, Facebook and Instagram. Acceleron is a biopharmaceutical company dedicated to the discovery, development, and commercialization of therapeutics to treat serious and rare diseases. The Company's leadership in the understanding of TGF-beta superfamily biology and protein engineering generates innovative compounds that engage the body's ability to regulate cellular growth and repair. Acceleron focuses its research and development efforts in hematologic, neuromuscular, and pulmonary diseases. In hematology, the Company and its global collaboration partner, Bristol-Myers Squibb, are co-promoting newly approved Reblozyl (luspatercept-aamt) in North America for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell transfusions and developing luspatercept-aamt for the treatment of chronic anemia in myelodysplastic syndromes and myelofibrosis. Acceleron is also advancing its neuromuscular program with ACE-083, a locally-acting Myostatin agent in phase 2 development in Charcot-Marie-Tooth disease and is conducting a phase 2 pulmonary program with sotatercept in pulmonary arterial hypertension. Follow Acceleron on Social Media: @Acceleron Pharma and Linked In. This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on historical performance and current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that future study results will be consistent with the results to date, that REBLOZYL (luspatercept-aamt) will be successfully commercialized for the indication for which it is currently approved, that Reblozyl may not achieve its primary study endpoints or receive regulatory approval for the additional indications described in this release in the currently anticipated timeline or at all and, if approved, whether such product candidate for such additional indications described in this release will be commercially successful. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol-Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol-Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2018, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol-Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise. This press release contains forward-looking statements about Acceleron’s strategy, future plans and prospects, including statements regarding the development and commercialization of Acceleron’s compounds, the timeline for clinical development and regulatory approval of Acceleron’s compounds, the expected timing for reporting of data from ongoing clinical trials, and the potential of REBLOZYL® (luspatercept-aamt) as a therapeutic drug. The words "anticipate," "believe," "could," "estimate," "expect," "goal," "intend," "may," "plan," "potential," "project," "should," "target," "will," "would," and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results could differ materially from those included in the forward-looking statements due to various factors, risks and uncertainties, including, but not limited to, that preclinical testing of Acceleron’s compounds and data from clinical trials may not be predictive of the results or success of ongoing or later clinical trials, that the results of any clinical trials may not be predictive of the results or success of other clinical trials, that regulatory approval of Acceleron’s compounds in one indication or country may not be predictive of approval in another indication or country, that the development of Acceleron’s compounds will take longer and/or cost more than planned, that Acceleron or its collaboration partner, BMS, will be unable to successfully complete the clinical development of Acceleron’s compounds, that Acceleron or BMS may be delayed in initiating, enrolling or completing any clinical trials, and that Acceleron’s compounds will not receive regulatory approval or become commercially successful products. These and other risks and uncertainties are identified under the heading “Risk Factors” included in Acceleron’s most recent Annual Report on Form 10-K, and other filings that Acceleron has made and may make with the SEC in the future. The forward-looking statements contained in this press release are based on management's current views, plans, estimates, assumptions, and projections with respect to future events, and Acceleron does not undertake and specifically disclaims any obligation to update any forward-looking statements.