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You can view it at the link below:View PDFIf you can not access the report, please contact ariana.lynn@thefastmode.com Get updates and alertsdelivered to your inbox The Policy & Resources policy letter comes a year after a letter of intent was signed between P&R member Jonathan Le Tocq and Biberach Mayor Norbert Zeidler Biberach’s mayor is now set to visit Guernsey for the Liberation Day 80th anniversary commemorations and it is hoped the Framework of Friendship will be signed during that visit Guernsey has long-standing ties with Biberach an der Riß in southern Germany The relationship began when British citizens not born in the Channel Islands were deported by German authorities during the Occupation About 1,000 British citizens and their families ended up in Camp Lindele in Biberach The modern relationship was developed in 1997 through reconciliatory moves from Biberach The new move is intended to formalise the long-standing relationship A framework of friendship arrangement between Guernsey and Biberach has the purpose of strengthening cultural social and economic ties between the two parties while formally recognising their shared history and reconciliation The framework does not go into specific detail about how its aims will be achieved such as encouraging meetings and exchanges of historical and cultural knowledge among educational institutions It also suggests that educational initiatives be facilitated to teach residents about the shared history of the town and the island You need to be logged in to comment. 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Tragedy struck in the southwestern state of Baden-Württemberg when a man died in a flooded basement apartment in Biberach district Days of stormy weather including lightning strikes, heavy rain and flash flooding, has affected areas of western, central and southern Germany since 03 June 2021 causing flooding in the state of Baden-Württemberg The town of Rot an der Rot recorded around 65mm of rain in 24 hours to 08 June while the town of Biberach an der Riß recorded over 40 mm of rain during the same period The government of Biberach district reported over 100 buildings damaged by flooding in the communities of Ellwangen In tragic circumstance a man died after becoming trapped in a flooded basement apartment in the town of Rot an der Rot “The situation in the affected communities is devastating…Our deepest condolences go to the relatives of the deceased I would particularly like to thank the around 500 emergency services who have been on duty since last night (07 June) and really give everything The willingness to help and solidarity on site is great We now hope that there will be no more rain and that the tense situation will relax a little in the next few hours.” Head of the Office for Fire and Disaster Protection in Biberach said that as of the afternoon 08 June the levels were falling slowly but steadily and the emergency services were embarking on clean-up operations in many places Flooding also affected Heilbronn District of Baden-Württemberg where the Fire Service was called out to over 250 missions to pump flooded cellars close flooded roads and clear flood debris including educational buildings have been flooded The Audi factory in Neckarsulm also saw some minor flooding Some buildings were also reported flooded in the city of Heilbronn One person was injured in a road accident blamed on the severe weather Richard Davies is the founder of floodlist.com and reports on flooding news Cookies | Privacy | Contacts © Copyright 2025 FloodList The state-of-the-art biologicals development centre (BDC) in Biberach provides attractive spaces for more than 500 researchers Boehringer Ingelheim developed a biologicals development centre (BDC) within its plant site in Biberach It is Europe’s largest development centre in biotechnology The facility is used for conducting advanced research to achieve therapeutic breakthroughs for the treatment of a wide range of conditions The foundation stone for the centre was laid in June 2018 and the plant was inaugurated in April 2023 Boehringer Ingelheim invested €350m ($384.6m) in the state-of-the-art facility The development centre complements the company’s investments in its global biopharmaceutical development network. The company has already invested in a cell culture plant in Vienna a new production facility for biopharmaceuticals in China and expanded production capacity in California The BDC is an addition to Boehringer Ingelheim’s campus in Biberach the company’s largest research and development (R&D) and biopharmaceuticals location with more than 7,000 employees The BDC at Biberach an der Riß is part of the company’s long-term plan to expand its biologic drugs development segment including the key therapeutic areas of immune-oncology and immunology the building provides a high-tech work environment for more than 500 scientists responsible for the development and formulation of Boehringer Ingelheim’s future biopharmaceutical products Researchers from various fields and three distinct development units namely analytical development biologicals (ADB) can work together within a single facility to conduct research and create antibodies and therapeutic proteins The facility provides the capacity to manufacture these substances ranging from small-scale laboratory production to providing supplies for clinical trials The facility consolidates biological analysis, process development and drug manufacturing for clinical trials departments as well as minimises the pathways and generating synergies The facility is also utilised to conduct biopharmaceutical drug development in addition to R&D increasing the overall development capacity It also created capacity for contract manufacturing The BDC allows for the production of a wide range of active ingredients ranging from laboratory scale to clinical stages I and II The Biberach plant produces medicinal proteins and antibodies from the cell cultures of mammals The company’s BioXcellence unit operates a pilot plant and two large-scale manufacturing plants for contract manufacturing at the site It offers an entire production chain that starts from DNA to fill and finish alongside customised contract development and manufacturing solutions The plant employs fed-batch processes as its core technology as well as offers perfusion processes in 2,000l fermenters established as an integral part of the commercial plant A single-use plant comprising bioreactors from 100l to 500l is also part of the plant in addition to a fully disposable downstream processing facility The facility manufactures clinical and commercial cell banks using good manufacturing practices (GMP) it has generated and released approximately 200 master Boehringer Ingelheim has established itself as one of the world’s biggest pharmaceutical companies the family-owned company operates with 181 subsidiaries and employs 53,000 people worldwide The company’s operations centre around the core business areas of human health With a focus on adding value through innovation it invests more than 20% of its net sales towards human pharmaceutical R&D Give your business an edge with our leading industry insights View all newsletters from across the GlobalData Media network The Biologics Development Center (BDC) will develop antibodies and therapeutic proteins and manufacture substances for clinical trials The €350 million ($386 million) figure is Boehringer Ingelheim’s largest single investment in Germany to date and the company said the Biberach an der Riß plant will account for around 50%of the firm’s research pipeline “With state-of-the-art laboratory and process equipment and a team of highly skilled scientists the BDC will have the necessary capabilities to develop and produce drug substance of therapeutic protein drug candidates ranging from initial lab-scale development to large-scale production for clinical studies providing a comprehensive solution for the entire early product life cycle up to clinical Phase II,” a spokesperson for Boehringer Ingelheim told BioProcess Insider “The focus is primarily on antibodies and therapeutic proteins which have the potential to revolutionize the way we treat diseases.” The BDC has a floor space of 34,500 square meters and according to the firm it has been designed to be consistent with its future strategy and R&D pipeline Boehringer Ingelheim says it significantly increases its power and development of biopharmaceutical capabilities in Germany “By focusing on biopharmaceuticals and dedicating substantial resources to this area we are further strengthening our capacity to deliver breakthrough therapies […] and we are committed to leveraging the world-class facilities and expertise at the BDC to develop drugs for patients in need,” the spokesperson said The facility will employ over 500 employees who will be responsible for developing the company’s future biopharmaceutical substances Boehringer Ingelheim will hire scientists from “multiple disciplines,” and they will have the ability to manufacture these substances from lab-scale to supply for use in clinical studies “As the portfolio had developed over the last years BI has already hired many employees over the last years who now find their home in the modern By fostering a culture of innovation and collaboration ensuring that Boehringer Ingelheim remains at the forefront of the industry,” said the spokesperson The news follows a U-turn by Boehringer Ingelheim on building a €1.2 billion ($1.32 billion) biologics plant in Bruck an der Leitha Journalist covering global biopharmaceutical manufacturing and processing news and host of the Voices of Biotech podcast I am currently living and working in London but I grew up in Lincolnshire (UK) and studied in Newcastle (UK) Got a story? Feel free to email me at [email protected] CSL Seqirus signs pandemic preparedness plan with European Commission Ins & Outs: Biopharma players shuffle c-suite ranks American made: Companies continue to emphasize US manufacturing Transforming Protein Production: Lonza’s Comprehensive Solutions for Therapeutic Innovation Registered in England & Wales with number 01835199 This website is using a security service to protect itself from online attacks The action you just performed triggered the security solution There are several actions that could trigger this block including submitting a certain word or phrase You can email the site owner to let them know you were blocked Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page About us | Advertise with us | Contact us The new €350 million biotechnology R&D centre is Boehringer Ingelheim’s largest single investment in Germany to date Boehringer Ingelheim has inaugurated its new Biologicals Development Center (BDC) in Biberach an der Riß The biopharmaceutical facility received €350 million in funding the company’s largest single investment in Germany to date “In our new [34,500 square metre] development centre we will conduct cutting-edge research at the most advanced level to achieve therapeutic breakthroughs,” explained Hubertus von Baumbach Chairman of the Board of Managing Directors at Boehringer Ingelheim biopharmaceuticals are one of the fastest growing drug sectors within the pharmaceutical industry These treatments offer therapies for many indications such as cancer announced that the site will develop next generation biological active substances As the largest European development centre for biotechnology the new high-tech biopharmaceutical facility provides workplaces for more than 500 employees Scientists from multiple disciplines and three different development units will collaborate under one roof to research and develop antibodies and therapeutic proteins They will have capabilities to produce these substances from lab-scale to supply for clinical studies Inauguration of the new facility is an additional milestone in further development of Boehringer Ingelheim’s Biberach campus, the company’s largest R&D and biopharma site The recent investment “sets a benchmark for the industry and serves as an essential addition to our global biopharmaceutical R&D network,” added Baumbach Boehringer Ingelheim has invested heavily in its R&D pipeline , By No comments yet All subscriptions include online membership giving you access to the journal and exclusive content Comment *document.getElementById("comment").setAttribute( "id" "a2f00c92a2113745a47adff6226a7e21" );document.getElementById("a9d92917df").setAttribute( "id" Write for us | Advertise with us European Pharmaceutical Review is published by: Russell Publishing Ltd.Court LodgeHogtrough HillBrasted © Russell Publishing Limited Website development by e-Motive Media Limited Necessary 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applications The cookie is used to store and identify a users' unique session ID for the purpose of managing user session on the website The cookie is a session cookies and is deleted when all the browser windows are closed.viewed_cookie_policyThe cookie is set by the GDPR Cookie Consent plugin and is used to store whether or not user has consented to the use of cookies It does not store any personal data.zmember_loggedThis session cookie is served by our membership/subscription system and controls whether you are able to see content which is only available to logged in users the French industrial start-up that recently successfully equipped the Canopée vessel with four OceanWings making it the first hybrid industrial cargo ship powered by wind With a height of 37 metres and a surface area of 363 m² each lowerable and patented vertical wingsail technology will help the ship cut fossil fuel consumption AYRO’s 37-m-high wingsails require a special solution due to their size especially regarding its electrical actuators Enter the Liebherr-Components team from Biberach an der Riss (Germany) The electric adjustment system consists of an adjustment module Each adjustment module contains a specific slewing bearing electric motors and brakes to operate the large wingsails fully automatically.Liebherr integrated all the relevant elements into the wingsails The Israeli military said it carried out airstrikes against Yemen's Hodeidah Port on Monday Belgium-based offshore installation services company DEME has completed the acquisition Havfram Thordon Bearings has seen its RiverTough tailshaft bearing solution surpass 500 installations in the workboat sector.Primarily… Jan De Nul has kicked off the installation campaign of the monopile foundations for RWE’s Thor offshore wind farm we excel in creating stunning illuminated yacht names and logos and cutting-edge LED and fiber optic solutions Maritime Reporter E-News is the maritime industry's largest circulation and most authoritative ENews Service delivered to your Email five times per week Drug Discovery and Development By | January 16 Sanofi announced it has entered into a strategic agreement with Boehringer Ingelheim for the manufacture of therapeutic monoclonal antibodies to reinforce Sanofi’s manufacturing capacity to support upcoming product launches 72 percent of Sanofi’s Research and Development projects are in biologics nearly half of which are monoclonal antibodies (mAbs) Sanofi will have access to Boehringer Ingelheim’s capabilities in Biberach an der Riss Germany to transfer and manufacture therapeutic mAbs Initial product transfers will begin in early 2015 “Boehringer Ingelheim is a highly capable and experienced partner to complement our continued alliance with Regeneron and the investments we are making in building our own internal capabilities as we prepare for a wave of potential new product launches in the coming years,” said Wolfram Carius “This collaboration reinforces Sanofi’s commitment to our strong biologics pipeline and will enable us to take the necessary steps to provide access to high quality therapeutic monoclonal antibodies to meet the needs of patients.” “We are looking forward to this collaboration with Sanofi This agreement reflects the strategy of Boehringer Ingelheim to be dedicated and committed to the manufacturing of highly innovative new biologic entities,” said Uwe Bücheler Corporate Senior Vice President Boehringer Ingelheim Biopharmaceuticals Source: Sanofi Copyright © 2025 WTWH Media LLC. All Rights Reserved. The material on this site may not be reproduced, distributed, transmitted, cached or otherwise used, except with the prior written permission of WTWH Media Privacy Policy | Advertising | About Us Metrics details Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare lung disorder involving production of autoantibodies against endogenous granulocyte–macrophage colony-stimulating factor (GM-CSF) This study aimed to identify biomarkers that could be used to monitor for aPAP particularly in patients treated with anti-GM-CSF antibodies Pre-specified biomarkers were evaluated between baseline and Day 120 in serum/plasma sputum and exhaled breath condensate from patients with aPAP and patients with chronic obstructive pulmonary disease (COPD) and asthma (not treated with anti-GM-CSF and with no evidence of aPAP) Pulmonary function tests were also performed 144 individuals were enrolled (aPAP: n = 34 and Krebs von den Lungen 6 and GM-CSF autoantibody ranges were higher in patients with aPAP compared with other populations lactate dehydrogenase and carcinoembryonic antigen ranges partially or completely overlapped across populations Most plasma biomarkers showed high sensitivity and specificity for detection of aPAP; GM-CSF and GM-CSF autoantibody concentrations demonstrated equivalent sensitivity for differentiating aPAP In addition to characteristic GM-CSF autoantibodies assessment of plasma GM-CSF may identify individuals at risk of developing aPAP Trial registration: EudraCT, 2012-003475-19. Registered 23 July 2012—https://eudract.ema.europa.eu/ patients receiving anti-GM-CSF therapy are theoretically at risk of developing iatrogenic aPAP Identifying a biomarker (or biomarker combination) indicative of aPAP would facilitate early identification of disease by triggering appropriate medical work-up to confirm or reject diagnosis and could help differentiate aPAP from other respiratory diseases This exploratory study was undertaken to determine levels and ranges of biomarkers potentially associated with aPAP which could be used alone or in combination to monitor for pulmonary alveolar proteinosis onset in healthy human subjects or in patients with underlying respiratory diseases receiving anti-GM-CSF antibodies therapeutically Findings will also extend understanding of the potential risk of iatrogenic pulmonary alveolar proteinosis in patients receiving anti-GM-CSF antibodies therapeutically and support clinical development of these treatments autoimmune pulmonary alveolar proteinosis; COPD Baseline demographic characteristics are shown in Table 1 men made up the majority of each group (64.7–75.0%) The proportion of current or ex-smokers was higher among patients with aPAP than healthy volunteers Patients with COPD were generally older and had worse lung function than the other populations Exclusion criteria for patients with COPD (never-smokers and patients aged < 40 years ineligible) and patients with asthma (current smokers ineligible) were reflected in study group characteristics Baseline severity classification of patients is shown in Table 1 disease severity or severe exacerbation was related to higher scores on symptom questionnaires (corresponding to uncontrolled symptoms/worse health) Inter-individual variability was generally higher in induced sputum samples than in serum/plasma/whole blood samples (Table 2) All biomarker levels in exhaled breath condensate samples at baseline were below lower quantification limits (data not shown) In most cases, serum/plasma GM-CSF values were sufficient to differentiate between aPAP and other groups (Additional File 1: Table S4) and CYFRA was necessary to discriminate between aPAP and asthma CEA and GM-CSF was necessary to discriminate between aPAP and COPD In serum/plasma samples, clinical factors did not add value, with GM-CSF being an adequate discriminating factor between patients with aPAP and all other groups (Additional File 1: Table S4) between three and six factors were required to discriminate between patients with aPAP and other populations these patient groups were also investigated since biomarkers may also be useful in patients at risk of developing aPAP induced by anti-GM-CSF therapy CEA and CYFRA either partially or completely overlapped across the different study populations; distinguishing aPAP based on just one of these biomarkers would be unreliable None of the biomarkers analyzed in induced sputum was a suitable aPAP identifier in its own right and biomarkers could not be detected in exhaled breath condensate Results from the symptom questionnaires support the findings of the pulmonary function tests with mean scores on the Asthma Control Questionnaire (ACQ) George’s Respiratory Questionnaire (SGRQ) highest/worst for patients with asthma or COPD with severe disease or experiencing severe exacerbation may help to identify patients most at risk of aPAP or differentiate aPAP from worsening of existing condition It will need to be determined whether patients receiving anti-GM-CSF antibodies have a reduction in plasma GM-CSF this could be the next step in utilization as a risk marker for aPAP in those patients This study has some limitations and findings are exploratory in nature The patient populations had some differences in baseline characteristics biomarker reference ranges should be taken as a first estimate and no confidence intervals were calculated for the limits of the reference ranges More data will be needed to establish reliable biomarker reference ranges the risk assessment for aPAP is still unclear as the time taken from development of low GM-CSF plasma levels to disease onset is unknown Further study of plasma GM-CSF levels in patients receiving anti-GM-CSF antibodies may help define the relationship between plasma GM-CSF and aPAP risk and delineate the usefulness of such an approach observational study was conducted at a single Italian center over 120 days (between October 2013 and September 2015) Longitudinal evaluation of pulmonary function and biomarkers in different biofluids was performed in four groups: aPAP Anti-GM-CSF therapies have been investigated in asthma and COPD and could theoretically induce iatrogenic PAP Patients with asthma and COPD not treated with GM-CSF were therefore included as a reference base The study was carried out in accordance with the principles of the Declaration of Helsinki the International Conference on Harmonization for Good Clinical Practice and local legal and regulatory requirements All participants provided written informed consent prior to study participation The local authority that approved the study on 11 February 2013 was the Ethics Committee at IRRCS Policlinico San Matteo Hospital Foundation (approval number: P-20120042069) Patients with COPD were aged 40–70 years; all other participants were aged 18–70 years at study entry. All participants were required to have a BMI between 18 and 35 kg/m2. Definitions of disease severity for patients with aPAP, COPD and asthma are described in Additional file 1: Supplementary Appendix 1 Patients had a current diagnosis of aPAP with consistent computed tomography findings (crazy-paving pattern in the lungs) and elevated levels (≥ 5 μg/mL) of GM-CSF autoantibodies aPAP was classified according to partial pressure of oxygen (PaO2) volumes as mild (asymptomatic; PaO2 ≥ 70 mmHg) or in stable remission (asymptomatic; PaO2 ≥ 70 mmHg with a whole lung lavage conducted 1–2 months prior to study entry) Patients with PaO2 < 60 were not included Participants had normal values on pulmonary function tests at screening were shown to be healthy by clinical laboratory tests and vital signs had not received GM-CSF in the previous 4 weeks Patients were either stable for at least 1 month or experiencing a severe exacerbation (defined as symptoms requiring hospitalization and/or change in COPD treatment for at least 3 days) Patients were required to be current smokers or ex-smokers with a smoking history of > 10 pack-years and not to have received GM-CSF in the previous 4 weeks and not to have a diagnosis of aPAP requiring actual or intended treatment with systemic corticosteroids or at least a doubling of previous daily doses of systemic corticosteroids Patients were non-smokers or ex-smokers with a smoking history of ≤ 10 pack-years who had stopped smoking at least 1 year prior to enrollment had not received GM-CSF in the previous 4 weeks and could not have a diagnosis of aPAP DLCO was measured in all participants at baseline Values are reported for DLCO% predicted and absolute measured values corrected for hemoglobin Spirometry (FEV1 and FVC) was performed in all participants at baseline FEV1% predicted and FVC% predicted values are also reported Biomarker levels were measured in biofluid samples (serum/plasma, induced sputum and exhaled breath condensate) taken at baseline, Day 60 and Day 120 (Additional file 1: Supplementary Appendix 3 and Table S1) Induced sputum was collected from participants with an FEV1% predicted ≥ 50% Stimulated and unstimulated values of GM-CSF-mediated CD11b and pSTAT5 expression on neutrophilic granulocytes were measured in whole blood and stimulation index was calculated as (stimulated value – unstimulated value)/unstimulated value Using the measured biomarker data in blood and induced sputum, reference ranges were calculated for each of the biomarkers in each of the four trial populations (Additional file 1: Supplementary Appendix 4) The safety of study procedures was assessed based on vital signs clinical laboratory tests and incidence of adverse events To analyze the potential diagnostic ability of biomarkers to distinguish between participants in the four study populations pairwise comparisons were made for biomarker values in blood and induced sputum samples where applicable Cut-off values were determined to estimate sensitivity to detect aPAP for a given specificity (≥ 80%) Receiver-operating characteristic curves were plotted to quantify the ability of each biomarker to predict the presence or absence of aPAP Multivariate statistical prediction models based on logistic regression were developed using: (a) biomarker values alone and (b) biomarker values in conjunction with established clinical variables (BMI lung function parameters) as potential predictors All biomarkers apart from GM-CSF autoantibody level were included in the models as GM-CSF autoantibody concentrations were higher in patients with aPAP than in all other study populations Inclusion would have added too much bias since it would have been the only predictor in the model resulting in perfect separation The aim was to identify alternatives to GM-CSF autoantibodies as these were also part of the diagnostic inclusion criteria for patients with aPAP Generally, Boehringer Ingelheim makes data that support the findings of studies available from https://trials.boehringer-ingelheim.com/ but restrictions apply to the availability of these data where anonymization cannot be ensured This is particularly the case for single-center studies like the study discussed in this publication Boehringer Ingelheim cannot share any additional data Diffusing capacity of the lungs for carbon monoxide Granulocyte-macrophage colony-stimulating factor Phosphorylated signal transducer and activator of transcription 5 Idiopathic pulmonary alveolar proteinosis as an autoimmune disease with neutralizing antibody against granulocyte/macrophage colony-stimulating factor Characteristics of a large cohort of patients with autoimmune pulmonary alveolar proteinosis in Japan The encephalitogenicity of T(H)17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF Granulocyte-macrophage colony-stimulating factor expression in induced sputum and bronchial mucosa in asthma and COPD The mechanism of GM-CSF inhibition by human GM-CSF auto-antibodies suggests novel therapeutic opportunities Clinical significance of serum anti-GM-CSF autoantibody levels in autoimmune pulmonary alveolar proteinosis Serum neutralizing capacity of GM-CSF reflects disease severity in a patient with pulmonary alveolar proteinosis successfully treated with inhaled GM-CSF Differences in the immunolocalization of surfactant protein (SP)-A and KL-6 in pulmonary alveolar proteinosis Clinical importance of bronchoalveolar lavage fluid and blood cytokines and Kerbs von Lungren 6 antigen in idiopathic pulmonary alveolar proteinosis Serum YKL-40 is a reliable biomarker for pulmonary alveolar proteinosis The clinical clues of pulmonary alveolar proteinosis: A report of 11 cases and literature review Clinical significance of anti-GM-CSF antibodies in idiopathic pulmonary alveolar proteinosis Serum KL-6 levels in pediatric patients: Reference values for children and levels in pneumonia KL-6 but not CCL-18 is a predictor of early progression in systemic sclerosis-related interstitial lung disease Third International Workshop on Lung Tumor and Differentiation Antigens: Overview of the results of the central data analysis randomised placebo-controlled trial to evaluate the efficacy and safety of an anti-GM-CSF antibody (KB003) in patients with inadequately controlled asthma GM-CSF as a therapeutic target in inflammatory diseases Therapeutic potential of treating chronic obstructive pulmonary disease (COPD) by neutralising granulocyte macrophage-colony stimulating factor (GM-CSF) Serum KL-6 is a predictor of outcome in pulmonary alveolar proteinosis Serum KL-6 in pulmonary alveolar proteinosis: China compared historically with Germany and Japan Serum and bronchoalveolar fluid KL-6 levels in patients with pulmonary alveolar proteinosis Pulmonary alveolar proteinosis during a 30-year observation Long-term follow-up of whole lung lavage in patients with pulmonary alveolar proteinosis Quantitative assessment of Pulmonary Alveolar Proteinosis (PAP) with ultra-dose CT and correlation with Pulmonary Function Tests (PFTs) A new scale to assess the severity and prognosis of pulmonary alveolar proteinosis Human GM-CSF autoantibodies and reproduction of pulmonary alveolar proteinosis Development and first validation of the COPD Assessment Test A self-complete measure of health status for chronic airflow limitation Development and validation of a questionnaire to measure asthma control Clinical and Laboratory Standards Institute (CSLI): EP28-A3C and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline--Third Edition PA: Clinical and Laboratory Standards Institute; 2010 Download references The authors would like to thank Professor Maurizio Luisetti (deceased) the initial principal investigator of this study This trial was funded by Boehringer Ingelheim International GmbH (BI) The authors did not receive payment for the development of the manuscript editorial support and formatting assistance for this manuscript was provided by Helen Keyworth and Micha Thompson and Rebecca Sutch of Amiculum Ltd BI was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE) All authors were involved in interpretation of the data and reviewed and revised the manuscript critically for important intellectual content All authors read and approved the final manuscript CS and AG are employees of Boehringer Ingelheim FM and BCT declare that they have no competing interests Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41598-022-11446-8 Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma. meeting today's requirements as well as tomorrow's Boehringer Ingelheim can fill and close up to 400 containers/min ranging from vials to single and double-chamber cartridges workers check the disposable tubes of the filling system.Microbes follow people everywhere—even into the highest-grade cleanrooms Isolators can provide a remedy by separating people and pharmaceuticals to ensure the highest purity standards for the aseptic manufacture of biopharmaceuticals Pharmaceutical manufacturer Boehringer Ingelheim’s new facility in Biberach an der Riss, Germany, fulfils those requirements, winning the 2014 Facility of the Year Award (FOYA) from ISPE the International Society for Pharmaceutical Engineering Equipped with filling and isolator technology from Bosch Packaging Technology the facility was recognized in the equipment innovation category for the successful implementation of a flexible and transparent production facility for biopharmaceuticals providing flexible and transparent production of biopharmaceutical products in all important dosage forms Boehringer Ingelheim is among the world’s top 20 pharmaceutical companies and marketing of high-quality therapies for use in human and animal medicine Boehringer Ingelheim operates Europe’s largest facility for the development and manufacturing of pharmaceuticals with biotechnologically produced active ingredients both for its own business and for contract manufacturing To increase its flexibility and capacity at this site the company decided to expand and modernize the production of biopharmaceuticals After two years of concept development and design studies the company initiated an ambitious project involving the construction of two ultramodern filling lines with a joint connection to two freeze dryers in an existing production building “Our goal was to create a flexible production area for the manufacturing of all important biopharmaceutical dosage forms It was supposed to meet today´s and future requirements for aseptic processing while allowing transparent and flexible production,” explains Dr Friedrich Haefele Vice President BP Fill & Finish Germany at Boehringer Ingelheim An 80-strong interdisciplinary project team worked on the implementation over a period of three years together with international providers of pharmaceutical infrastructure and equipment The supplier developed and installed two complete filling lines with the corresponding isolator technology consisting of an FLC line as well as an MLD combi line designed to fill liquid and freeze-dried products into vials The MLD combi line also processes single and double-chamber cartridges one chamber is for the freeze-dried active ingredient “Bosch provided the technology we needed: five separate isolators—from a single source and at a competitive price The combi line enables us to switch between different container types and adjust production to meet both our needs and those of our customers,” explains Joachim Schweizer we also reduced our cleanroom footprint while integrating the systems into our premises.” Additional components were provided by the Bosch subsidiaries Pharmatec and Moeller & Devicon Pharmatec manufactured several sterile filtration modules to filter the product immediately before filling as well as two mobile CIP (Cleaning in Place) systems These are used to prepare the cleaning media for the filling machines Moeller & Devicon automated both the transport and removal of the cartridges with several handling units The centerpiece of the first project phase is the FLC 4080 which enables Boehringer Ingelheim to fill and close up to 400 containers/min the vials are washed in a Bosch RRN 3084 washing machine and then sterilized in a Bosch HQL 4360S tunnel Four separate isolator segments ensure aseptic conditions during the filling and closing process as well as the loading of the freeze dryers Glove ports and separate HVAC and decontamination systems make sure that staff and products are protected at all times A VRK 6160B capping machine from Bosch with a capping capacity of 600 containers/min completes the 61-meter-long vial line While the vial line was undergoing the qualification process The combi line features an MLD 3081 filling and closing machine which is also equipped with isolator technology it can fill and close single and double-chamber cartridges at a rate of up to 300/min Further components of the combi line are two RRN 3083 washing machines—one for vials and one for cartridges—as well as an HQL 4680S sterilization tunnel a tray-loading unit is used for cartridges and a VRK 3080 capping machine for vials The combi line also has a connection to the freeze dryer What’s special about the system configuration is its flexible transport concept “We can switch between different dosage forms flexibly and they always remain well-protected through the isolators,” explains Dr In the same year the second project phase was completed Boehringer Ingelheim received approval from the European Medicines Agency (EMA) to manufacture vials with freeze-dried substances Additional authorizations for foreign markets The manufacturing lines are organized in a U-shaped configuration which enables fast and flexible response to production requirements at maximum operating times and are visible to both visitors and customers “The ISPE’s Facility of the Year Award and the new facility concept highlight our leading position as a manufacturer of biopharmaceutical drugs under aseptic conditions—and Bosch Packaging Technology—has made an important contribution to this success.” Automotive supplier Handtmann has announced the production of further components for vehicle manufacturing using the aluminum die casting process Following its successful launch in fall 2024 the so-called megacasting will be expanded at the Biberach site in Baden-Württemberg Managing Director of the responsible Albert Handtmann Metallgusswerk GmbH & Co confirmed at the Global Giga Casting Congress in Kassel the first components for the battery area will now be followed by tailgates and the front and rear ends “We expect major changes in the supplier market as a result of the transformation in the automotive industry,” said Dirk Seckler “Handtmann has decided to take on the role of innovation leader Megacasting is a production process that enables the manufacturing of large and complex structural components in a single cast The main advantages of large cast components for customers include a high level of functional integration reduced manufacturing complexity and lower procurement and logistics costs Numerous process steps in production are saved and labor-intensive joining and post-processing steps such as welding and adhesion are avoided the weight of the car body is significantly reduced which is particularly relevant for electric vehicles Handtmann significantly reduces production time in automotive production improves material efficiency and also increases the structural integrity of vehicles Handtmann provided information on Thursday in Kassel about its expectations for market development the proportion of cast aluminum in vehicles will increase from the current 130.3 kg to 142.5 kg in 2030 Handtmann anticipates that combustion engine and transmission component housings will be less relevant in competition in the future High competitive pressure is expected particularly for standard components such as electric motor housings as there is already sufficient capacity for these components in the supplier market the winners of the transformation include EV components Development expertise and new technologies such as megacasting can provide an advantage for these components The Biberach-based company is taking the opportunity to focus on large and complex new products in particular thereby setting itself apart from the competition The Handtmann Group of Companies decided to invest in the first megacasting die casting machine during the Corona period and invested a double-digit million euro amount which is in high demand in the USA and Asia Handtmann is the first European supplier to use megacasting in series production The Group is aiming to strengthen its German production facilities and its European customers and business partners with this investment Megacasting - The new process and its use at Handtmann The Handtmann Group The Handtmann Group is a globally operating technology company in the processing industry with approximately 4,700 employees 3,300 of whom work at the company’s headquarters in Biberach an der Riß and a people-centered approach are at the heart of this family-owned enterprise The group is divided into six business units with autonomous management structures: Lightweight Metal Casting A holding company serves as the leadership Handtmann generated a revenue of 1.3 billion euros the company’s owners enable substantial investments in research and development as well as production facilities This approach supports sustainable and qualitative growth The Handtmann Group currently operates in over 100 countries with its own production facilities the company celebrated its 150th anniversary in 2023 www.handtmann.de Lightweight Metal Casting Division As part of the Handtmann Group the Lightweight Metal Casting division is a strategic partner in the development and production of aluminum die-cast components for the automotive industry Handtmann manufactures structural components using the emerging megacasting technology The subsidiary is the largest family-owned lightweight metal foundry in Europe https://www.handtmann.de/leichtmetallguss I would like to receive the bi-weekly Foundry-Planet newsletter with all latest news Plus the special newsletters – all can be cancelled anytime and at no cost German supplier Handtmann Systemtechnik has unveiled a modular LFP battery system that can provide a capacity of up to 1.3 MWh it is particularly suitable for robust applications in heavy vehicles ships and stationary energy storage systems Handtmann Systemtechnik describes its new battery system as flexibly scalable to meet individual customer requirements in terms of energy demand and installation space The liquid-cooled solution utilises lithium iron phosphate cells which are combined into modules of 13 kWh each these modules can then be combined to form battery sets with several megawatt hours “It is possible to connect up to 56 battery boxes – seven in series and eight in parallel Individual configurations with up to 16 master boxes and a maximum capacity of 1.34-megawatt hours can be realised,’” the company explains in an accompanying press release A minimum system consists of one master box and two battery boxes The voltage options range up to a maximum of 1000 volts DC Handtmann Systemtechnik aims to create a solution primarily for construction machinery marine applications and stationary energy storage systems with high storage requirements The system has thus been tested on an in-house test bench in Biberach an der Riss fluctuating temperatures and cycle stability An integrated safety concept should also include a ‘safety box’ that continuously monitors the system at cell “When we developed this battery system our focus was on the simple combination of different system configurations,” says Markus Michelberger KG was founded in 2003 and is thus one of the newest business units within the Handtmann Group the unit sees itself as a technology and system partner for the automotive industry and supplies components for combustion engines (‘charging charge air routing and cooling as well as thermal management’) as well as for electric vehicles – such as high voltage storage housings and battery systems press-n-relations.com (in German) I agree with the Privacy policy electrive has been following the development of electric mobility with journalistic passion and expertise since 2013 we offer comprehensive coverage of the highest quality — as a central platform for the rapid development of this technology CH Boehringer Sohn AG & Co KG is the parent company of the Boehringer Ingelheim pharmaceutical group which was founded in 1885 by Albert Boehringer in Ingelheim am Rhein they are a global group of companies producing pharmaceuticals for the worldwide market With reported revenue of $17.9 billion in 2017 they are one of the largest pharmaceutical companies in the world the company’s research focuses around the areas of respiratory diseases oncology and diseases of the central nervous system One of its early commercial successes was the reproduction of lactic acid created by the human body future Nobel Prize winner Professor Heinrich Otto Wieland set up the company’s research department Karl Thomae GmbH re-opened in Biberach an der Riss with a staff of 70 – the foundation for its future expansion it acquired Pfizer’s veterinary programme and a subsidiary had been established in Greece: Boehringer Ingelheim Hellas the company has 146 subsidiaries around the globe and its corporate headquarters are in Frankfurt It employs more than 50,000 people with a long list of successful products in prescription medicine Join our newsletter to receive regular updates on our stories Orbis Terra Media GmbH will use the information you provide on this form to be in touch with you and to provide Newsletter updates Please let us know all the ways you would like to hear from us: You can change your mind at any time by clicking the unsubscribe link in the footer of any email you receive from us or by contacting us at info@tharawat-magazine.com We will treat your information with respect For more information about our privacy practices please visit our website you agree that we may process your information in accordance with these terms a strategic system partner for the automotive industry in aluminum and magnesium casting will start the in-house series production of inverter housings for electric vehicles Automation specialist Grenzebach will provide the friction stir welding (FSW) equipment including pre-series monitoring of the component as well as supply and integration of the right welding system The commissioning of the FSW gantry machine at the Handtmann site in Biberach an der Riß is scheduled for summer 2022 Solution from a single source: From engineering to commissioning The partner project has already started in 2019 with the engineering of the inverter housing: In cooperation with a Tier-1 of the automotive industry Grenzebach assisted in the development and manufacturing of the prototypes After the successful development phase with the Tier-1 Handtmann was nominated as supplier and is nowresponsible for producing the inverter housing The pre-series production of the components has started at the end of November 2021 at Grenzebach's Hamlar site Handtmann will still rely on Grenzebach's expertise beyond this phase: By the middle of the year a DSM 14-10 FSW gantry machine will be delivered to the automotive supplier enabling Handtmann to weld the inverter housings in-house in the future "Being a direct development partner to the automotive industry the technological development and casting implementation of intelligent light metal cast components is a significant core competence of our light metal casting business unit Thanks to Grenzebach's many years of experience and knowhow in friction stir welding we are able to quickly expand our portfolio with another lightweight design concept and develop our production processes in a future-oriented way" Project Management at Handtmann Metallgusswerk Produktions-GmbH & Co High-performance welding technology for e-mobility adds: "Lightweight construction for e-mobility requires high-performance and innovative welding technologies In our successful cooperation with Handtmann Grenzebach demonstrated the capability to supply welding technology as a reliable solution and journey partner which not only meets the requirements of the automotive industry We are happy about the trust in our expertise and technology." The next EUROGUSS will be held in Nuremberg from 8 to 10 June 2022 For all details please go to: www.euroguss.de Interested in more NF-Lightmetal and die casting related information Please check out Event-Connector for EUROGUSS 2022 Click here to open the tool About friction stir welding at Grenzebach Friction stir welding (FSW) is the innovative welding process for joining materials durably and robustly FSW can be optimally integrated into industrial se-ries production Grenzebach is your automation partner from the very beginning Different equipment concepts are available – from gantry machines with customer-specific working ranges to robots Developing processes and providing friction tools are part of Grenzebach’s holistic approach About Grenzebach Grenzebach is a leading automatization solution provider for the global glass building material and intralogistics market the company develops new application areas the automatization of industrial additive manu-facturing or digital networking Grenzebach ranks among the international technology leaders in its markets The global manufacturing footprint with production sites in Germany as well as additional worldwide locations ensure customer support on-site More than 3,000 systems installed in more than 55 countries stand for quality and reliability Since the company opened its doors over 60 years ago With an export ratio of more than 90 percent Carina Bruckmaier (UMC Utrecht) explored lymphocyte dynamics in various tissue sites in homeostasis and during imbalanced states her research on the life span of some of the lymphocyte subcategories revealed some interesting new insights The human immune system has the capacity to keep the number of lymphocytes in the body relatively consistent despite a constant exposure to bacteria and viruses The immune system is working to maintain this balance: new lymphocytes are created continuously A balance between production and loss of lymphocytes is essential to keep the immune system healthy up to old age To understand how lymphocyte populations are generated, maintained and subsequently lost, and how these populations are disrupted and restored during disease, it is important to gain a quantitative understanding of lymphocyte dynamics. In her thesis, Carina Bruckmaier (Center for Translational Immunology UMC Utrecht) explored lymphocyte dynamics using heavy water labeling T-cell receptor (TCR) sequencing and functional characteristics of lymphocytes in various tissue sites in homeostasis and during imbalanced states Due to the challenges of using T cells in chimeric antigen receptor (CAR) therapy a subset of innate immune cells specialized in anti-tumor and anti-viral immune responses They quantified the lifespan of NK cells in vivo using deuterated water and found it to be 94 days - longer than previously reported in the literature Tthese results suggest that NK cells are much longer-lived than commonly thought which could offer a more positive outlook on and aid the implementation of CAR-NK cell therapy Carina Bruckmaier concluded: “These new insights into the functionality, dynamics, and diversity of lymphocytes throughout the body do not only improve our understanding of the immune system in health and disease, but also pave the way for the development of novel therapeutic approaches.” Carina Bruckmaier (1993, Biberach an der Riss, Germany) defended her PhD thesis on June 3, 2024 at Utrecht University. The title of her thesis was “Grow old or die young - Lymphocyte dynamics in humans”. Supervisor was prof. José Borghans PhD and co-supervisor was Kiki Tesselaar PhD (both Center for Translational Immunology, UMC Utrecht). Subscribe to BuzzFeed Daily NewsletterCaret Down20 Extraordinary Photos That Won The Sony World Photography AwardHere are the powerful winning pictures from the 2015 Sony World Photography Awards in all their photographic glory. In the summer of 2014, Monrovia, Liberia, became the epicenter of the West African Ebola epidemic, the worst in history. Although previous rural outbreaks were more easily contained, once the virus began spreading in Monrovia's dense urban environment, the results were described by Doctors Without Borders as "catastrophic." As President Sirleaf declared a state of emergency, photographer John Moore was there to document the harrowing sights. Omu Fahnbulleh stands over her husband Ibrahim after he fell and died in a classroom used for Ebola patients. A Doctors Without Borders health worker in protective clothing carries a child suspected of having Ebola at the MSF treatment center on Oct. 5, 2014, in Paynesville, Liberia. The girl and her mother, both showing symptoms of the virus, survived and were released about a week later. A woman crawls towards the body of her sister as Ebola burial team members take her away. "I took this image while paragliding over Räumliches Bildungszentrum, in Biberach an der Riss. It was an early morning in May, it had rained all night, and it was perfect conditions to get good contrasts. I took five flights between 2013 – 2014 trying to get the perfect shot, with perfect contrast and shadows, until I finally got it this morning in May 2014." —Armin Appel Svetlana's dark and moody series is about people who live on the edges of the city of St. Petersburg. “This is the back alley of my grandmother’s house in Alor Setar, Kedah, Malaysia. I shot this during Chinese New Year last year when the sky is the clearest and brightest with stars.” —Yong Lin Tan The 2015 Professional category is aimed at professional photographers around the globe and is selected from different genres of photography. A girl tweets during her prom. For many teenagers, social media has become an integral important outlet of who they are. The colorful umbrellas create amazing geometric patterns which contrast dramatically with the golden sand and azure-colored sea. From the air it is possible to see how almost every inch of sand is used on a busy summer's day on the Adriatic coastline. Molotov cocktails have been the weapon of choice for the Euromaidan protesters in Kiev. Using fire to their advantage, the protesters were able to defend their barricades, extend their lines, and fortify their positions. In order to set fire to tanks, armored vehicles, buses, and tires in opposition to local cops, Kiev’s protesters used thousands and thousands of Molotov cocktails, inspiring and mobilizing people throughout the city to collect as many bottles as possible. Philippe passes most of his time in his beautiful house in one of the most dangerous neighborhoods in Charleroi, Belgium. Troilo's series The Dark Heart of Europe captures the vision of postindustrial Europe and the social unease felt among its citizens. A burial team from the Liberian Red Cross sprays disinfectant over the body of a woman suspected to have died of the Ebola virus on Aug. 14, 2014, in Monrovia, Liberia. Teams retrieved dozens of bodies from all over the capital of Monrovia, where the Ebola virus spread quickly last summer. Li Fan's beautiful and dramatic black-and-white images show the ethnic Yi people living in the great Liangshan mountains of China. Bolivia is proud of being the Latin American country with the highest number of actively working women. Every Sunday in the poorest neighborhood of La Paz, female farmers from the countryside get in the ring for a public fight. Wearing traditional clothes and bowlers, Bolivian Valkyries deal with even more demanding fights once they get off the ring, raising their children all by themselves and working between the fields and the urban street markets. Mg Ko, 20 years old. A Shan farmer with his cow in Lui Pan Sone Village, Kayah State, Myanmar. Scott captures a deeply personal documentary project on mental illness. This picture was taken as part of the social project Uniendo Caminos, in the chapel Our Lady of Lujan in Villa La Carcova, Jose Leon Suarez, Buenos Aires. This is one of the most dangerous neighborhoods in the country. Mapping with a pyrograph the melting away of the Lewis Glacier on Mount Kenya. The flame line shows the Lewis Glacier's location in 1963. While parishes have been twinned with different communities in the past this will be the first time Guernsey as an island has been twinned with a town the southern German town had two prisoner-of-war camps including internment camp Ilag V-B for allied civilians the two communities have sought to make links of friendship and culture Policy & Resources external relations lead Jonathan Le Tocq and Bailiff Richard McMahon were invited to the town by the mayor for a service this weekend as both communities marked 78 years since German camp inmates were liberated Deputy Le Tocq said the idea of the two communities being twinned formally had been worked on behind the scenes for the last few months and P&R was supportive particularly to be able to say to the town of Biberach that we are grateful to them for their hand of friendship over the years,’ he said A commemorative service was held yesterday and the letter of intent was signed As Guernsey has not been twinned with another community before there is still some preparatory work needed to bring to agreement formally into place Deputy Le Tocq said he was pleased to sign the document ‘It is quite an important thing for future generations,’ he said ‘Survivors do pass away and we don’t want this to be forgotten.’ He expected it to take a few months to bring the agreement in but he was hopeful it would be in place by the end of the year More than 800 Guernsey people were interned at the camp during the war One of the island’s links with Biberach for many years was the Guernsey Friends of Biberach friendship group Former deputy Gloria Dudley-Owen was a member and was born in the Biberach camp during the war ‘I think it’s a good thing,’ she said about the twinning ‘It will be interesting to see what it will mean for us.’ as it had previously been said it would not be possible to the island to twin with Biberach She added that it would be important to understand what responsibilities and costs would come from signing a formal twinning agreement Biberach an der Riss is a town in Baden-Wurttemberg in southern Germany It is also twinned with Tendring district in Essex non island-born Channel Islanders were deported to an internment camp near the town The Biberach camp housed more than 1,300 Allied civilians during the war Men were kept separate from their families and the camp was cramped In April 1945 there was some resistance from the Nazi forces before the camp was liberated The Channel Islanders were all repatriated back to the UK from the end of May The Guernsey Deportees’ Association was formed in the late 1990s when a group travelled to southern Germany for a reconciliation week Since then there has been a strong link between the town and Guernsey You need to be logged in to comment. If you had an account on our previous site, you can migrate your old account and comment profile to this site by visiting this page and entering the email address for your old account We'll then send you an email with a link to follow to complete the process Liebherr-Components has developed a gear ring rope winch for the RL-K 7500 offshore crane which is specially designed for heavy lifting tasks at sea With a tare weight of 180 tonnes the ZSW 2400 is the largest and heaviest rope winch offered by Liebherr It is particularly noted for its high availability and long service life which is reached by a redundant drive system and an innovative winding mechanism that protects the rope The Liebherr Pactronic® system makes it extremely energy-efficient Integrated in the complete system with hydraulic drives and control system the rope winch enables active heave compensation (AHC) for the subsea crane Oil and gas extraction systems are being installed directly on the sea floor more and more often which increases the requirement for high-performance subsea cranes This was why Liebherr-Components decided to develop a rope winch for heavy loads and extreme depths The winch for the new Liebherr RL-K 7500 subsea crane should also be designed for a long service life and its mechanical principle of operation should be simple and robust Proven rope winch design with innovative features During the development period of about one year were able to draw on decades of experience in the field of large rope winches They decided to use a conventional rope winch design without additional winders because this rope winch design can raise and lower the full load in any position The rope drum with a diameter of 2.9 m is hydraulically driven on both sides by gear rings A total of eight Liebherr DMVA 165/165 double motors on the primary drive side and eight DPVO 165/DMVA 165 pump motors and 16 DAT 500 slewing drives on the storage side is required to exert the high rope pull force of 270 tonnes with single reeving and to manage the active heave compensation The drum with Lebus grooving holds eight rope layers with a rope diameter of 100 mm The rope winch can therefore move loads up to 200 tonnes at depths up to 2,000 m and loads up to 95 tonnes at depths up to 3,400 m High availability and energy efficiency with redundant drive system The redundant drive design with two load paths can still lift the load in the event of failure of one drive side This guarantees maximum safety and very high overall availability of the crane in any operating condition of the rope winch The secondary drive side acts as an energy recovery system while a load is being lowered are designed to operate as hydraulic motor while lifting a load and to operate as pumps during lowering or while idling to charge an energy accumulator (gas pressure tank) The innovative Liebherr Pactronic® system was originally developed for the mobile harbour cranes manufactured at Nenzing Austria by the Liebherr division Maritime Cranes and has been specially adapted for active heave compensation (AHC) in subsea cranes The Pactronic® system allows up to 60% of the power required for AHC operation to be taken from stored energy The resulting energy efficiency of the system is unparalleled in the market Wide range of applications in the modular system Another advantage is that the new rope winch is based on a modular system The Lebus half shells on the rope drum and the insertion plates This allows exactly the same winch to use ropes with different diameters (to a maximum of 100 mm) and it makes applications as deep as 3,400 m possible This greatly increases the range of possible applications of the rope winch It is suitable for a very wide range of lowering and lifting operations in subsea applications such as subsea mining or oil and gas drilling Active heave compensation – refined technology Because subsea lifting and underwater work is possible only when the sea is quiet only very small time windows are available for such operations This can be optimised by decoupling the load from the vertical motion of the ship The Liebherr maritime crane division has developed a control for offshore cranes to meet the requirement for active heave compensation (AHC) which compensates for the wave motion by accurately calculated counter-motions Traditional AHC systems that compensate for the motion with hydraulic cylinders lead to high wear on the winch and there is also the risk that the system may become blocked The newly developed deep-sea winch from Liebherr-Components has innovative winding mechanisms that protect the rope The rope drum was designed with an increased number of windings to reduce the number of rope layers The winding behaviour with reference to a diagonal pull in the required range of 0.8 to 1.5 degrees is maintained by an axial motion of the winch This ensures that the rope is seamlessly wound on the special grooves and the winding capacity is fully used The reduced material requirements for the end plates and the drum mantle saves up to 50% in weight compared to other designs with fewer windings and more rope layers The innovative design of the winch significantly increases the rope service life and availability which contributes to a great reduction in operating costs Daily news and in-depth stories in your inbox The Pioneers of Offshore Engineering GustoMSC part of NOV’s Marine and Construction business is recognized for providing advanced design & engineering consultancy for mobile offshore units and reliable equipment and technical knowledge into realistic & innovative ideas The performance of new and existing jack-ups The German goalkeeper played for a number of local teams such as FV Biberach SG Mettenberg and SSV Ulm 1946 before joining Vfb Stuttgart at the tender age of 12 He grew in stature and played for the German Under 16 national team in the Autumn of 2008 in a game against Macedonia This game drew him to the attention of Manchester City who invited him over to England  He joined City in the summer of 2009 and despite appearances in the Under 18 and Under 21 side - returned to Germany in 2011 without having broken into the first team In the summer of 2011 he was initially loaned to Mainz 05 - but this deal was made permanent in January 2012  He spent the first 18 months playing for the Mainz reserve side in a regional league He made his senior debut on the 1st December 2012 against Hannover 96 after keeper Christian Wetklo was sent off for a second bookable offence The following season (2013-14) he became the first choice keeper and picked up a further 95 appearances at Mainz in the following three season German boss Jurgen Klopp wasted no time at the end of the 2015-16 season in bringing Loris in and Karius signed a five year deal  He was handed the number 1 shirt which had been vacant for twelve months Karius took the gloves at the start of Liverpool's pre-season training as Simon Mignolet had not returned from the Belgian side after the European Championships of 2016 By October 2016 Jurgen Klopp had declared that Karius was Liverpool's number 1 keeper but after a couple of mistakes in December the player was dropped with Simon Mignolet returning to the starting line up Simon Mignolet began as first choice with Karius selected to play in Liverpool's Champions League and domestic cup games He played in the 4-0 win over Arsenal in the Premier League after Mignolet was rumoured to have had a late night watching the boxing Liverpool topped their Champions League group and as the festive period approached Karius began getting more game time in the Premier League again At the beginning of 2018 Loris Karius played in the FA Cup 3rd round win over Everton he then went on to be named by Klopp as Liverpool's first choice keeper.  Simon Mignolet expressed his disappointment with the World Cup ahead but the Belgian didn't help his cause when he played in the FA Cup 4th round home defeat against West Brom Karius's introduction coincided with the arrival of Virgil van Dijk and Liverpool improved defensively in the second half of the season.  Karius helping the club secure a top four place in the League and reach the Champions League Final the final in Kiev against Real Madrid would turn out to be a pivotal moment in his career In the 51st minute after receiving the ball he attempted to roll the ball out to a defender but gave it straight to Karim Benzema who gave Madrid the lead Liverpool levelled the score before a wondergoal from Gareth Bale.  But with the reds chasing the game he made another error - misjudging the flight of the ball from Gareth Bale who saw his 35 yard shot go in the net off the gloves of the keeper Karius was clearly emotional at the final whistle.  A week later after assessment by doctors in a Boston specialist centre it was announced that he had been suffering with concussion leading up to the game.  Minutes before the opening goal replays showed that he had been elbowed in the head by Benzema During pre-season he then made another error against Tranmere Rovers leading to a conceded goal.  Liverpool bought Alisson Becker from Roma for £55M relegating Karius to position of reserve keeper.  However he made an appearance off the bench at the home friendly against Torino and received warm applause from the Anfield crowd Reds maintain pre-season winning record despite Karius error – Tranmere 2-3 Liverpool Loris Karius was suffering concussion in Champions League final Salah and Ramos play pivotal roles in Kyiv LFC Reds: LFC Fan discussions on Loris Karius More in the LFC Shop The independent Liverpool FC website and forums Dtsch Arztebl Int 2009; 106(34-35): 565; DOI: 10.3238/arztebl.2009.0565azu dem Beitrag von PD Dr. med. Till Neumann, Janine Biermann, Dr. med. Dr. rer. pol. Anja Neumann, Prof. Dr. rer. pol. Jürgen Wasem, Prof. Dr. med. Georg Ertl, Prof. Dr. med. Rainer Dietz, Prof. Dr. med. Raimund Erbel in Heft 16/2009 Alarmiert durch Daten des Statistischen Bundesamtes berichten Neumann und Koautoren (1) über „Diagnosen Todesursachen und Kosten“ der Herzinsuffizienz die „heutzutage eine der häufigsten und kostenintensivsten chronischen Erkrankungen“ sei Wenn die Autoren pauschal über die dafür angefallenen Kosten in Deutschland 2006 und künftige Trends nachdenken dass die Herzinsuffizienz keine chronische Erkrankung ist Vielmehr handelt es sich um ein klinisches Syndrom mit charakteristischen Symptomen denen ganz unterschiedliche Krankheiten zugrunde liegen Somit sollte nicht undifferenziert über „die Herzinsuffizienz“ geschrieben werden wenn eine chronische Form gemeint ist und eine konkrete nosologische Zuordnung der vorgelegten heterogenen statistischen Zahlenkolonnen nicht möglich ist Die akute und chronische Links- wie auch die akute und chronische Rechtsherzinsuffizienz sowie deren Kombination (globale Herzinsuffizienz) haben unterschiedliche Diese weisen auf vielfältige Veränderungen und Erkrankungen des linken und des rechten Herzens sowie des Herzbeutels hin die sich auf drei Ursachengruppen für eine Herzinsuffizienz verteilen: dekompensierte Herzhypertrophie myogene Herzinsuffizienz und Perikardveränderungen Eine Betrachtung der Grundleiden für eine Herzinsuffizienz erscheint jedoch geboten wenn medizinische und wirtschaftliche Gesichtspunkte zu dem häufigsten Grund für Krankenhausaufenthalte erörtert werden E-Mail: horst.nizze@med.uni-rostock.de 1Neumann T, Biermann J, Neumann A et al.: Heart failure: the commonest reason for hospitalization in Germany—medical and economic perspectives [Herzinsuffizienz: Häufigster Grund für Krankenhausaufenthalte. Medizinische und ökonomische Aspekte]. Dtsch Arztebl Int 2009;106: 269–75. VOLLTEXT Halle M, Berg A, Hasenfuss G: Sekundärprävention der koronaren Herzerkrankung. Körperliches Training als Therapiepfeiler. Dtsch Arztebl 2003; 100(41): A 2650–6. VOLLTEXT Nizze H, Bernateck M: „Lebensstilintervention“ – Mephistos Rat. Dtsch Arztebl 2004; 101(28-29): A 2057. VOLLTEXT Werden Sie Teil der Community des Deutschen Ärzteblattes und tauschen Sie sich mit unseren Autoren und anderen Lesern aus Unser Kommentarbereich ist ausschließlich Ärztinnen und Ärzten vorbehalten Anmelden und Kommentar schreibenBitte beachten Sie unsere Richtlinien Der Kommentarbereich wird von uns moderiert Kommentare können nur von Abonnenten verfasst werden, die einen vollen Namen in ihrem Benutzerprofil hinterlegt haben dass Sie als Abonnent ausweist und hinterlegen Sie Ihren vollen Namen in Ihrem Profil Erhalten Sie Zugriff auf nicht öffentliche Inhalte Kommentieren Sie Inhalte und lesen Sie Kommentare anderer Benutzer Informieren Sie sich täglich (montags bis freitags) per E-Mail über das aktuelle Geschehen aus der Gesundheitspolitik und der Medizin Bestellen Sie den kostenfreien Newsletter des Deutschen Ärzteblattes Immer auf dem Laufenden sein ohne Informationen hinterher zu rennen: Der tagesaktuelle Newsletter Reinhardtstr. 34 · 10117 BerlinTelefon: +49 (0) 30 246267 - 0Telefax: +49 (0) 30 246267 - 20E-Mail: aerzteblatt@aerzteblatt.de