Join us at the Akustika Fair at the Nuremberg Exhibition Centre from April 4-6 Meet The Strad team at stand F08 and pick up a free copy of the magazine The Strad Directory Jobs The cellist took up the role in November 2024 having previously held teaching roles in Cologne and Maastricht Cellist Gabriel Schwabe © Studio Monbijou Read more news stories here Gabriel Schwabe has accepted a position of cello professor at the Music Academy in Lübeck The cellist has been teaching in the post since November 2024 and has previously held roles at the University of Music and Dance in Cologne and the Conservatorium Maastricht ’I’m excited to join the faculty of the Academy of Music Lübeck a school with a rich history of string teaching,’ Schwabe told The Strad. ’Following in the footsteps of giants like Shmuel Ashkenasi Lynn Harrell or David Geringas is a wonderful challenge and I look forward to embracing the school’s traditions as well as continuing to explore my very own approach to teaching in this new and inspiring setting.’ German-Spanish cellist Schwabe is a laureate of three of the world‘s most prestigious cello competitions: the Grand Prix Emanuel Feuermann in Berlin the Concours Rostropovich in Paris and the Pierre Fournier Award in London As a soloist he has worked with orchestras such as the London Philharmonia the Malmö and Norrköping Symphony Orchestras and the NCPA Orchestra Beijing with conductors such as Marek Janowski Michael Sanderling and Marc Soustrot.  He has been a chamber music partner to artists such as Pinchas Zukerman In 2010 he gave his recital debut at London’s Wigmore Hall He is a regular guest at festivals such as the Jerusalem Chamber Music Festival Amsterdam Biennale and Schleswig-Holstein Music Festival.  He has released seven albums as an exclusive recording artist for Naxos, among them a recording of the Elgar and Bridge Cello Concertos with the ORF Vienna Radio Symphony Orchestra and Christopher Ward 2024 will see the release of the complete Beethoven Sonatas and Variations with Nicholas Rimmer.  Schwabe received his musical education from Catalin Ilea at the University of Arts in Berlin and with Frans Helmerson at the Kronberg Academy with further inspiration from Janos Starker  He is married to violinist Hellen Weiß and plays a cello by Giuseppe Guarneri ’ex-Boettcher’ Listen: The Strad Podcast #107: back to basics with cellist Gabriel Schwabe Read: Cellist Jeffrey Zeigler rejoins the faculty of the Mannes School of Music in New York In The Best of Technique you’ll discover the top playing tips of the world’s leading string players and teachers It’s packed full of exercises for students plus examples from the standard repertoire to show you how to integrate the technique into your playing The Strad’s Masterclass series brings together the finest string players with some of the greatest string works ever written Masterclass has been an invaluable aid to aspiring soloists chamber musicians and string teachers since the 1990s The Canada Council of the Arts’ Musical Instrument Bank is 40 years old in 2025 This year’s calendar celebrates some its treasures including four instruments by Antonio Stradivari and priceless works by Montagnana A chance to watch this epic work in its entirety Who better to write music for cello than cellists themselves  Ben Michaels writes about commissioning six solo cello pieces by cellists Cellist Amber Den Exter is receiving treatment following a car crash last month in Houston which resulted in serious spinal injuries and paralysis 38 violists under the age of 30 have been selected to produce a video recital for the chance to progress to the competition’s live rounds in November Anna Boysen Lauritsen takes up the role of director while founder Jacob Shaw steps aside into the role of artistic director Site powered by Webvision Cloud A game that inspired more curiosity than confidence Borussia Dortmund officially opened the 2024-25 season in Hamburg against fourth-tier Phönix Lübeck in Nuri Sahin’s first competitive game as BVB manager The Pokal game got off to a sizzling start as new signing Waldemar Anton tapped in a lovely Pascal Groß corner with less than three minutes on the clock Dortmund extended their advantage at the half-hour mark as Karim Adeyemi (playing as a makeshift striker) won a penalty which captain Emre Can emphatically converted with Dortmund enjoying over 80% of the ball (though not really threatening the opposition) but we saw the best goal of the game in first-half stoppage time with Brandt showing exceptional control to collect a long ball from new man Groß and finish beyond Lübeck keeper Leonhard The Oberliga side actually managed to pull one back on 55 minutes with centre-back Iloka pouncing on a sloppy Brandt giveaway and taking advantage of some clueless defending to power a wonderful finish past Kobel Our three-goal cushion was restored less than 10 minutes later as both the newly-introduced wide players combined Couto playing Duranville in behind to slot home though we nearly suffered some nasty shocks with Lübeck hitting the aluminium twice off corners late on Sahin opted to leave both Beier and Haller on the bench This meant that Karim Adeyemi was the nominal sole striker in a new 3-2-4-1 shape with one dropping deep and the other looking to stretch the Lübeck backline with a run in behind while Brandt was given a free-roaming 10 role Can and Groß comprised the black and yellow engine room Anton and Schlotterbeck the three central defenders While this shape is well-suited to the kind of quick passing and possession-oriented football that Sahin is looking to implement we looked unused to it; despite the relative lack of pressure from our opponents the passing was slow and disjointed and players were often poorly positioned in the buildup This was also reflected in the goal we conceded with the backline all at sea despite their numerical advantage but I think it’s going to take some time before we’re fluent in his language we relied on the fact that our players were fitter and capable of more brilliance than theirs (plus a little help from the aluminium); while this approach works against Phönix Lübeck it remains to be seen how we’ll fair against Bundesliga opposition This is at least partially attributable to the apparent foreignness of our new shape but it was clear that last season’s problems with creativity continue to trouble us our 88% possession yielded a paltry five shots (one a penalty) with our starting wide players registering a combined total of: one shot Our goals came from long balls and set pieces (sound familiar?) While the threat from wide areas improved after the introductions of Duranville and Couto (who combined for our fourth) I’m certain that the tiring Lübeck backline played a role in the apparent improvement with Sabi taking on the active shuttling role and Groß offering the deeper playmaking option I’ve no doubt this will improve as the boys familiarise themselves with the new approach Our starting XI consisted of two debutants in Waldemar Anton and Pascal Groß Waldi ghosting in unmarked at the back post to tap home a wonderful Groß corner making the assist for Brandt’s wondergoal later on in the half as well new right-back Yan Couto made the assist for young Julien Duranville making only his fourth appearance as a Dortmund player We also got a glimpse of Maxi Beier off the bench with the new striker showing his ability to make good runs in behind Image source: Eisemann N, Bunk S, Mukama T et al., Nature Medicine 2025 (CC BY 4.0) also highlight the potential of AI to reduce the workload of radiologists without compromising diagnostic quality.  Image source: University of Lübeck; photo: private evaluated data from over 460,000 women who participated in the MSP between 2021 and 2023 across 12 screening sites in Germany Approximately half of the mammograms were analyzed using AI while the other half were assessed through traditional double reading by radiologists “Our initial aim was to demonstrate that AI-based evaluations are equivalent to human assessments,” explained Prof principal investigator and Director of the Institute of Social Medicine and Epidemiology at the University of Lübeck and UKSH the findings exceeded our expectations: AI significantly improves breast cancer detection rates.” The study revealed that AI identified 6.7 cases of breast cancer per 1,000 women screened compared to 5.7 cases per 1,000 detected through traditional methods This equates to one additional cancer case detected per 1,000 women screened the rate of women referred for further testing remained stable with 37.4 per 1,000 for AI assessments compared to 38.3 per 1,000 for traditional double readings emphasized the global significance of these findings: “The PRAIM study highlights the immense potential of AI to enhance screening programs worldwide This evidence will elevate discussions about integrating AI into healthcare systems to a new level.” Measuring the calcium build up in the arteries of the breast researchers have developed an AI-generated score for predicting cardiovascular disease in women from their mammograms Another key finding of the study is the potential for AI to improve efficiency in breast cancer screening Simulations suggest that if all cases flagged as normal by AI were not reviewed by human readers the breast cancer detection rate would still be 16.7% higher the number of unnecessary recalls could be reduced by 15%.  Given that radiologists in Germany currently analyze 24 million individual images annually the implementation of AI could significantly alleviate their workload “We hope that the higher detection rates enabled by AI will improve outcomes for women with breast cancer This will be the focus of future investigations,” said Prof Breast cancer is the most common cancer among women in Germany screens over 3 million women aged 50 to 75 annually Despite the high accuracy of double readings some breast cancer cases remain undetected AI-based systems have the potential to address this diagnostic gap while simultaneously reducing the burden on radiologists.  The PRAIM study represents a significant step forward in integrating AI into clinical practice Its findings underscore the transformative potential of AI to enhance cancer detection and ultimately contribute to better outcomes for patients Future research will focus on evaluating the long-term impact of AI on patient prognosis and its integration into routine clinical workflows.  Current AI systems for detecting breast cancer from mammography exams are more likely to produce false-positive results in black women and older patients Despite their improving diagnostic accuracy medical AI systems are often met with skepticism by radiologists seem more inclined to embrace this technology AI-supported screening for breast cancer can detect more cancer cases compared with traditional screening and find more invasive cancers at an early stage This website uses cookies to give our readers the best website experience. Please refer to our privacy policy to find out how we use cookies and how you can edit your preferences. GK: Gregor Kobel - Kobel is expected to start his fourth season at Borussia Dortmund in goal against Lübeck. The Swiss goalkeeper has so far put on scintillating displays and will hope to continue his fine run of form. Even though he is no longer the vice-captain he will still be expected to be among the leading group of the club RB: Yan Couto - The 22 year old Brazilian right-back is expected to make his competitive debut on Saturday He played the first-half of the friendly against Aston Villa and will have to fight for his position as Julian Ryerson is another option for the role Couto appears set to start the season at right-back CB: Waldemar Anton - The new signing from Stuttgart is also expected to make the starting XI on Saturday After his excellent season with the Swabians Anton will hope to cement himself as a regular starter at Borussia Dortmund CB: Nico Schlotterbeck - After the departure of Mats Hummels, Schlotterbeck will now be expected to be the main man in central defence for Borussia Dortmund. He will also hope to start ahead of Niklas Süle on Saturday although the former Bayern man could also be in contention after a solid pre-season Left-Back: Ramy Bensebaini - With Yan Couto’s signing there are two solid players for the right-back position Bensebaini is yet to convince since his move from Borussia Mönchengladbach It will be interesting to see if Sahin goes with the Algerian international or Ryerson in that role on Saturday © 2025 Minute Media - All Rights Reserved The content on this site is for entertainment and educational purposes only Betting and gambling content is intended for individuals 21+ and is based on individual commentators' opinions and not that of Minute Media or its affiliates and related brands All picks and predictions are suggestions only and not a guarantee of success or profit If you or someone you know has a gambling problem crisis counseling and referral services can be accessed by calling 1-800-GAMBLER GK: Gregor Kobel - Kobel is expected to start his fourth season at Borussia Dortmund in goal against Lübeck. The Swiss goalkeeper has so far put on scintillating displays and will hope to continue his fine run of form. Even though he is no longer the vice-captain CB: Nico Schlotterbeck - After the departure of Mats Hummels, Schlotterbeck will now be expected to be the main man in central defence for Borussia Dortmund. He will also hope to start ahead of Niklas Süle on Saturday DM: Emre Can - Even though his influence has decreased Can remains the Borussia Dortmund captain and will start in the number six role against Phönix Lübeck The Germany international will hope to dominate proceedings in midfield can bring a lot of fresh input to the side ability to create chances and versatile profile he can be the leader BVB will need in this transitional season AM: Julian Brandt - The newly appointed Borussia Dortmund vice-captain will have his sights set on another strong season with Borussia Dortmund He will look to set the tone from the number ten role this weekend AM: Marcel Sabitzer - After establishing himself as a key player for Borussia Dortmund during his first season with the club the Austrian international will have his sights set on a strong sophomore campaign Sabitzer could be in contention to play in the free attacking role on Saturday although Jamie Gittens could also be a candidate for the spot ST: Maximilian Beier - Beier is one of the best and most exciting signings BVB have made in recent years he could be used in a variety of different roles over the course of the season It will be interesting to see if he slots straight into the starting XI Sebastien Haller could also be an option for the striker's role on Saturday LW: Karim Adeyemi - After months of transfer speculations it looks like Adeyemi will be staying at BVB This means that he will probably get the nod for the left wing position The young German has at times shown what he is capable of He just needs to do it more consistently now Upadacitinib as New Treatment for Giant Cell Arteritis Filling the Gap: Creating a Prognostic Staging System for Patients Treated With Neoadjuvant Chemotherapy RFK Jr.’s Vaccine Policies Spark Alarm Among Public Health Experts Editorial Policy Advertising Contact Us eNewsletters Contribute Career Center MashupMD Blood Cancers Today Cancer Nursing Today GU Oncology Now Urban Health Today Too many automated requests from this network The project from a cultural alliance known as Kein Spaß mit Nazis (No Fun With Nazis) will stand against the creeping rise of right-wing extremism and fascism A protest rave against the rise of the far-right in Germany is set to take place in the northern city of Lübeck this Saturday Scheduled to run from 6PM - 10PM in the Marienkirchhof plaza it has been organised by a cultural alliance calling itself Kein Spaß mit Nazis The event has been given the name Bass gegen Hass (Bass Against Hate) and will include a music programme curated by local promoter SUPERKUNSTFESTIVAL The rally will take place a day before citizens vote in Sunday's federal election Current polls show the conservative Christian Democrats leading with the far-right group Alternative for Germany (AfD) in second The more left-leaning Social Democrats are polling in third place we position ourselves clearly and unambiguously against xenophobia and right-wing ideology Freedom and democracy have always been the best signposts for a cosmopolitan society and culture is its voice of praise and warning." Find more information about Saturday's rally here Back in 2018, far-right supporters at an AfD rally were outnumbered four to one by raving protestors at a demonstration in Berlin In 2023, thousands of Berlin ravers attended a protest event against the planned expansion of the A100 motorway The World Heritage Centre is at the forefront of the international community’s efforts to protect and preserve World Heritage partnerships for conservation Ensuring that World Heritage sites sustain their outstanding universal value is an increasingly challenging mission in today’s complex world where sites are vulnerable to the effects of uncontrolled urban development Our Partners Donate Take advantage of the search to browse through the World Heritage Centre information Lübeck – the former capital and Queen City of the Hanseatic League – was founded in the 12th century and prospered until the 16th century as the major trading centre for northern Europe It has remained a centre for maritime commerce to this day Despite the damage it suffered during the Second World War consisting mainly of 15th- and 16th-century patrician residences public monuments (the famous Holstentor brick gate) Ancienne capitale de la Ligue hanséatique et reine de la Hanse elle a été fondée au XIIe siècle et fut jusqu'au XVIe siècle la métropole du négoce pour toute l'Europe du Nord Elle reste encore aujourd'hui un centre de commerce maritime spécialement avec les pays nordiques Malgré les dommages qu'elle a subis durant la Seconde Guerre mondiale la structure de la vieille ville est conservée avec ses résidences patriciennes des XVe et XVIe siècles ses monuments publics (notamment la célèbre porte fortifiée en brique de la Holstentor) ses églises et ses greniers à sel إنها العاصمة القديمة للتحالف (الهانزي) التجاري وملكة الهانزا لقد تأسست المدينة في القرن السابع وبقيت حتى القرن السادس عشر مدينة التبادلات التجارية لكل أوروبا الشمالية لا تزال حتى اليوم مركزاً للتجارة البحرية ولا سيما مع الدول الشمالية على الرغم من الأضرار التي لحقت بها خلال الحرب العالمية الثانية، لا تزال بنية المدينة القديمة قائمة بمقرات النبلاء التي تعود إلى القرنين الخامس عشر والسادس عشر وبنصبها العامة (لا سيما الباب الشهير المعزز المصنوع من القرميد القادم من هولتنستور) وكنائسها ومخازن الملح فيها 吕贝克，汉萨同盟(the Hanseatic League)的前首都和皇后城，建于公元12世纪，作为北欧的重要商业中心曾一度繁荣 直到16世纪。今天，这里仍是海上商贸中心（尤其与北欧国家的海上贸易）。尽管在第二次世界大战中受到了一定的损毁，这座老城的基本城市结构还是保留了下来，这点从15世纪至16世纪建造的贵族居所，历史古迹（如著名的豪斯顿砖门）、教堂和盐场等都能够看出来。 бывшая столица и главный город Ганзейского союза как главный центр торговли на севере Европы В наше время Любек остается центром морской торговли общественные здания и сооружения (включая знаменитые кирпичные ворота Хольштентор и соляные склады) Antigua capital y ciudad reina de la Liga Hanseática Lübeck fue fundada en el siglo XII y hasta el siglo XVI fue la principal metrópoli comercial de la Europa Septentrional Actualmente sigue siendo un importante centro de comercio marítimo sobre todo con los países nórdicos Pese a los daños sufridos durante la Segunda Guerra Mundial se ha conservado la estructura de la ciudad antigua con sus mansiones señoriales de los siglos XV y XVI sus depósitos de sal y sus monumentos públicos como la famosa puerta fortificada de Holstentor Founded in 1143 on the Baltic coast of northern Germany Lübeck was from 1230 to 1535 one of the principal cities of the Hanseatic League a league of merchant cities which came to hold a monopoly over the trade of the Baltic Sea and the North Sea The plan of the Old Town island of Lübeck with its blade-like outline determined by two parallel routes of traffic running along the crest of the island dates back to the beginnings of the city and attests to its expansion as a commercial centre of Northern Europe the richest quarters with the trading houses and the homes of the rich merchants are located The very strict socio-economic organization emerges through the singular disposition of the Buden small workshops set in the back courtyards of the rich hares to which access was provided through a narrow network of alleyways (Gänge) Lübeck has remained an urban monument characteristic of a significant historical structure even though the city was severely damaged during the Second World War including the most famous monumental complexes- the Cathedral of Lübeck the churches of St Peter and St Mary and especially the Gründungsviertel the hilltop quarter where the gabled houses of the rich merchants clustered Selective reconstruction has permitted the replacement of the most important churches and monuments Omitting the zones that have been entirely reconstructed the World Heritage site includes three areas of significance in the history of Lübeck The first area extends from the Burgkloster in the north to the quarter of St Aegidien in the south a Dominican convent built in fulfilment of a vow made at the battle of Bornhöved (1227) contains the original foundations of the castle built by Count Adolf von Schauenburg on the Buku isthmus The Koberg site preserves an entire late 18th-century neighbourhood built around a public square bordered by two important monuments the Jakobi Church and the Heilig-Geist-Hospital The sections between the Glockengiesserstrasse and the Aegidienstrasse retain their original layout and contain a remarkable number of medieval structures Between the two large churches that mark its boundaries - the Petri Church to the north and the Cathedral to the south - the second area includes rows of superb Patrician residences from the 15th and 16th centuries with its salt storehouses and the Holstentor reinforces the monumental aspect of an area that was entirely renovated at the height of the Hansa epoch (about 1250 to 1400) when Lübeck dominated trade in Northern Europe the third area around St Mary’s Church and the Market Square bear the tragic scars of the heavy bombing suffered during the Second World War Criterion (iv): As outstanding examples of types of buildings the most authentic areas of the Hanseatic City of Lübeck exemplify the power and the historic role of the Hanseatic League The preserved quarters of the Old Town show in their unity the medieval structure of the Hanseatic Town and represent a high-ranking European monument The overall impression of the Old Town is reinforced by individual architectural highlights of ecclesiastical and profane character whereas the combined effect is revealed through the unique town silhouette with the seven high church towers The heart of the Old Town is surrounded by water on all sides and consisting mainly of 15th and 16th century Patrician residences its layout is clearly recognisable as a harmonious complete masterpiece and its uniquely uniform silhouette is visible from far The laws and regulations of the Federal Republic of Germany and the State of Schleswig-Holstein guarantee the consistent protection of the Hanseatic City of Lübeck The large number of historic monuments and the Old Town island are protected by the Act on the Protection and Conservation of Monuments in the federal state of Schleswig-Holstein The Monument Preservation Plan is the basis for town planning and specific architectural interventions the historic centre of Lübeck is protected by a preservation statute and a design statute; even the quarters of the late 19th century surrounding the Old Town are protected by preservation statutes The regional development programme of the federal state of Schleswig-Holstein ensures the protection of the view axes and the silhouette of the World Heritage property The City of Lübeck is responsible for the management of the World Heritage property The coordination between the stakeholders is organised by a World Heritage commissioner within the municipal structure in order to duly indicate potential threats to the Outstanding Universal Value and to ensure the integration of relevant issues into the planning procedures an integrative monitoring approach and a sustainable development of the World Heritage property this differentiated protective system guarantees an efficient preservation of the historical substance of the property To protect and sustain the Outstanding Universal Value a buffer zone and additional view axes outside the buffer zone are in place to ensure the long-term protection and sustained preservation of the important views and of the structural integrity external experts meet regularly in consultative bodies to monitor quality and discuss suitable solutions in town planning and construction practice Regarding the tourism and visitor management a tourism development concept (TDC) forms the basis for strategic activities.  Take a look around the northern German shop I like working undisturbed with few distractions so I found a place two miles outside the city of Lübeck in northern Germany The building is next to a church and the priest occupies around half the space I worked for five years in a tiny house nearby where the ceilings were less than two metres high so I had to sit down to play the violin Then in 2017 I asked if I could move my workshop into the empty part of the church house So I’ve been here for seven years and I’ve been able to customise it to my own needs… Already subscribed? Please sign in We’re delighted that you are enjoying our website you can try an online subscription to The Strad completely free of charge Sign up now to read this article in full and you’ll also receive unlimited access to premium online content including the digital edition and online archive for 7 days Free trial No strings attached – we won’t ask for your card details To enjoy the best in-depth features and analysis from The Strad’s latest and past issues You’ll also enjoy regular issues and special supplements* and access to an online archive of issues back to 2010 Subscribe * Issues and supplements are available as both print and digital editions Online subscribers will only receive access to the digital versions TV: None (US), Sky Go (Germany), everywhere else here There are legal means listed for you to watch the game Use those and don’t share any illegal streams in the comments We’re all tolerant people; we all get frustrated at a bad call the ref makes or react to some foul that the opposing team makes just think them through before posting them No abusing of other commentators or match officials racist and/or homophobic comments and replies will result in immediate blocking and banning of future participation though Vox Media may earn commissions for products purchased via affiliate links Your Ads Privacy ChoicesIMDb, an Amazon company© 1990-2025 by IMDb.com, Inc. A total of 1.6 million tonnes of decommissioned weapons grenades and artillery and machine gun ammunition lie at the bottom of the Baltic and North Seas all these weapons were taken from German and Allied arsenals by the barge load and dumped in the Bay of Lübeck as part of German disarmament All these discarded weapons have serious consequences as the metal shells and casings of bombs and cartridges corrode and release explosives Carcinogens and mutagens end up in the water and in the food chain - in fish and mussels and eventually on our plates "The German government is investing EUR 100 million in environmental protection "We have to act now while the ammunition is still intact enough to be recovered." we need an approach that allows us to salvage and dispose of munitions on an industrial scale 24/7." The experience gained from this pilot project should lead to a safe overall concept for working on the high seas.  SeaTerra is responsible for recovering piles of ammunition from the seabed as well as boxes of unidentified ammunition "First we scan the area using magnetometers to collect data," said Guldin three ships equipped with special technology A vessel equipped with Dynamic Positioning (DP) also known as Dynamic Positioning System (DPS) acts as the main starting point for the salvage operation Vessels with DPS can hold a position without anchoring or mooring thanks to a computer-controlled system for automatic positioning we lower a camera and gripper system as well as a diving team to identify any ammunition that can be handled safely and can be put into baskets." A grenade Around 95 per cent of the arms  are safe to handle and can be picked up by the gripper "The gripper is suspended from a crane and is brought into an optimum gripping position The contact pressure can be adjusted - from five to 250 kilos - to gently lift the various objects into the basket without causing an explosion." Achieving such sensitivity was a real challenge The gripper is supported by a remote-controlled underwater robot or crawler which examines the seabed and collects small objects such as bullets The finds are sorted and documented aboard the other ships. "We draw up a data sheet for every recovered object," said Guldin. "Most of the recovered ammunition is brought ashore for destruction and handed over to the Society for the Disposal of Chemical Warfare Agents and Legacy Armaments (GEKA)." The remainder is taken to a so-called wet storage facility for disposal The Port of Lübeck is a key piece of infrastructure in the Hamburg Metropolitan Region and far beyond around 25.6 million tonnes of seaborne goods were handled on Lübeck's quays Most ferries and cargo ships set sail for Sweden and Finland or arrive from the region Latvia and Lithuania are also important destinations Efficiency is a big issue in Lübeck: "We want to make better use of our space and get more out of it The aim should be to use the space fully before sealing new areas," said Michael Siemensen who is responsible for strategic port development at the Lübeck Port Authority Data can be transmitted in real time - and every minute counts in the Port of Lübeck where cargo sometimes has to be unloaded or loaded onto a ship in just two hours "Cargo" can mean anything from cars to truck trailers new and used vehicles and products such as cardboard Everything has to be in the right place at the right time: "Our long-term goal is a digital twin that provides all the information in real time It is about knowing what is where and how to get it to the right place at the right time," said Siemensen Procedures are now being digitised and networked as exemplified by the EVE42 robot Around 1,600 spaces are available for unaccompanied truck trailers at Skandinavienkai the hauliers do not park the trailers in allocated individual spaces but in rows of 40 to 60 spaces: "The truck drivers usually bring one trailer and often take another with them a trailer may not always be parked in a predetermined row of blocks but next to one that has to be picked up," Siemensen pointed out A search begins before freight is loaded onto a ship The EVE42 robot scans rows in the quay autonomouslyand updates the booking system i.e. The front of the trailer and even handwritten identifiers are being read successfully Problems arise with  autonomous driving and are now being addressed with the University of Lübeck Professor Georg Schildbach from the university's Autonomous Systems Lab said: "I assume that we will be able to achieve the goal of autonomous driving in the port within six months." The robot is just one of many projects underway in the Port of Lübeck Trailers will soon be arriving by both lorry and train Digital systems will automatically identify trailers Is it time-critical and where is the best place to park it Trucks can be automatically detected on entering the port and the data compared to quay usage it can be automatically diverted to another area until more space is available This digitisation strategy should lead to rapid The Port of Lübeck brings scientists on board for individual projects The Port of Lübeck is also investigating possible sources of funding it is difficult to say when the port will go fully digital it is easier for software and machines to take over in a pure container port like Hamburg the mix of cargo and the time factor make the Port of Lübeck special Trailers are loaded onto the ship by tractor units while ferry passengers drive their cars themselves loading and unloading occurs simultaneously fully automated loading and unloading by machine requires large time buffers given the level of precision and speed required."agu/kk/pb Europäisches Hansemuseum and our media Medienpartners broadcaster NDR and the Lübecker Nachrichten newspaper.   Presscontact:Hanseatic City of Luebeck - Nordic Film Days LuebeckJulia Kainz, PR Agency filmcontactpresse@nordische-filmtage.de+49 (0) 30 27908700 Download this press release as PDF Stay connected all year round: Become a member © 2025 Nordische Filmtage Lübeck Internet-Realisation, Design und Content-Management: CONVOTIS Lübeck GmbH We use external content from third-party providers such as video streaming services Consent to activation is voluntary and can be revoked at any time These cookies allow us to understand how visitors behave on our website This allows us to keep improving our website The first day of the scientific program will comprise a Teaching Day designed to provide first insights into the composition and basic functions of the complement system to those new to the field The Teaching Day will be paralleled by a Satellite Symposium at which distinguished lecturers from industry basic science as well as clinicians will discuss the role of C3 C5 and their cleavage products as targets in inflammatory diseases The Satellite Symposium is in line with the vore EMCHD 2024 program focusing on recent developments in the complement field to translate basic scientific advancements into novel therapeutic approaches to combat human diseases The scientific program will be complemented by a social program aimed at giving you a taste of Lübeck the Nordic beauty with impressive red brick historical monuments There will also be a Hanseatic gala dinner in Travemünde Lübeck's famous seaside resort on the Baltic Sea CONTACT Universität zu LübeckRatzeburger Allee 16023562 LübeckTel. +49 451 3101 0Fax +49 451 3101 1004UniversitätsklinikumSchleswig-Holstein (UKSH) Tel. +49 451 500 0IMPRINT Volume 2 - 2022 | https://doi.org/10.3389/frsip.2022.883696 This article is part of the Research TopicImmersive and Interactive Audio for Extended RealityView all 5 articles we evaluated a microphone array with six microphones mounted on a pair of glasses we conducted two listening experiments comparing four rendering methods based on acoustic scenes captured in different rooms2 The evaluation includes a microphone-based stereo approach (sAB stereo) a beamforming-based stereo approach (sXY stereo) beamforming-based binaural reproduction (BFBR) and BFBR with binaural signal matching (BSM) the perceptual evaluation included binaural Ambisonics renderings which were based on measurements with spherical microphone arrays In the EMA experiment we included a fourth-order Ambisonics rendering while in the glasses array experiment we included a second-order Ambisonics rendering In both listening experiments in which participants compared all approaches with a dummy head recording we applied non-head-tracked binaural synthesis with sound sources only in the horizontal plane The perceived differences were rated separately for the attributes timbre and spaciousness Results suggest that most approaches perform similarly to the Ambisonics rendering and microphone-based stereo were rated the best for EMAs and BFBR and microphone-based stereo for the glasses array Alternative approaches for the binaural reproduction of non-spherical array configurations are therefore required Several approaches have been proposed in the literature and are reviewed below who introduced a beamformer whose output is first-order Ambisonics signals (SH signals after radial filtering) Although the eXMA approach is a promising method eXMA was still in the optimization phase and is thus not further evaluated in this study This section introduces the microphone arrays and the data used for quantitative and perceptual evaluation it presents an overview of the fundamental theory of the binaural rendering approaches We chose to evaluate the approaches based on two different array configurations which are introduced in the following sections Microphone distribution of the EMA with six microphones (left) and eight microphones (right); Both have a center microphone exactly in the front (the direction of the arrow) The microphones used for AB stereo are indicated with “A” and “B” Only the EMA with eight microphones has microphones at ϕ =90° and ϕ =270° A diagram of the glasses array and its approximate microphone positions The array has one microphone exactly at the front (4) two at the back of the temple arms used for AB stereo one additional microphone at the right temple arm (1) This figure and the microphone positions are not a depiction of any current or future product For the comparative Ambisonics renderings in the quantitative and perceptual evaluation we employed SMA impulse responses measured under the exact same conditions as for the EMAs and glasses array we decided to render capture from an Eigenmike at the fourth order Since the employed database only includes 29th order SMA measurements we again applied resampling in the SH domain at N = 29 to the 32-microphone Eigenmike sampling scheme It should be mentioned that the resampled signals have the same sampling grid as the original Eigenmike measurements the radius of the original SMA (0.0875 m) cannot be adjusted to that of the Eigenmike (0.042 m) leading to slightly different aliasing effects we rendered 8-channel OctoMic data of the second order The general idea of the BFBR approach is to filter and sum each microphone signal x(ω)=[x1(ω),…,xM(ω)]T with the beamforming filters c(ω)=[c1(ω),…,cM(ω)]T which shows binaural signals calculated with the BFBR method from simulated array signals of a single plane wave impinging on an EMA6 from the frontal direction The BFBR method was performed with different numbers of beams the frontal HRTF is depicted as the dashed black line The figure shows that with increasing the number of beams the spectral roll-off compared to the frontal HRTF increases we used 32 uniformly distributed MD beams for binaural reproduction as preliminary listening tests demonstrated the best results for our array geometries The spectral roll-off was equalized with a minimum phase filter which compensates for the deviation of the transfer function of a reference microphone from the transfer function of the BFBR output from a single plane wave impinging on the array from the frontal direction Magnitude spectra of frontal binaural signals rendered with BFBR with different numbers of beams based on a single plane wave impinging on an EMA6 from the frontal direction a frontal HRTF of a KU100 dummy head for the frontal direction is depicted for BSM the array signals x(ω) are filtered and summed with pre-calculated filters c(ω)l,r leading to the binaural signals b(ω)l,r one set of filter coefficients is required for each ear separately To calculate the BSM filters it is assumed that the sound field consists of L acoustic events (sound sources) s(ω)=[s1(ω),…,sL(ω)]T the binaural signals a listener would be exposed to in the sound field are with hl,r=[h1(ω)l,r,…,hL(ω)l,r]T being the HRTFs for the directions of the sound sources s The BSM filters can be calculated by minimizing the error it is favourable to use microphone locations close to the positions of the listener’s ears uniform distribution of the microphones along the equator has advantages both EMAs have uniformly distributed microphones only the EMA8 has microphones exactly at ϕ = 90° and ϕ = 270° the microphones closest to the ears are on the back of the glasses’ temple arms For the AB stereo approach, we directly used the impulse responses of the AB microphones without any processing or equalization. The AB microphones on the EMAs are depicted in Figure 1. Again, it is worth mentioning that the EMA8 has microphones at ϕ = 90° and ϕ = 270°, while the EMA6 does not. For the glasses array case, we used the microphones on the temple arms of the glasses (labeled A and B in Figure 2) steering to (ϕ = 45° θ = 90°) and (ϕ = 315° Since the beams originate from the center of the array the beamforming-based XY stereo also can hardly produce any ITD cues we did not apply any post-processing or equalization We adapted both methods from the stereo recording with microphones To emphasize that we simulated these techniques with microphone arrays we refer to them as sAB (simulated AB) and sXY (simulated XY) in the following The comparative Ambisonics renderings were calculated with the ILDs and ITDs of the KU100 HRTFs are depicted by the black dashed line as a reference The ITD curve of the Ambisonics rendering matches the reference curve quite well followed by the curves for BSM and sAB stereo sXY stereo produces some notable excursions and seems to perform the worst This supports the assumption that beamforming-based XY stereo can hardly synthesize ITDs sAB stereo matches the reference curve the best whereas BSM and Ambisonics perform similarily to each other The ILD curve of sXY stereo exhibits some outliers specifically near 45° and 315° Both BFBR and sXY ILD curves are very jagged This might be due to the beams calculated with few microphones which exhibit side-lobes In contrast the BSM or Ambisonics ILD curves are quite smooth ITDs and ILDs of the EMA6 array using different binaural reproduction approaches The reference values (black dashed lines) were calculated from the KU100 HRTFs sAB and BSM both exhibit a dip at the top of the ILD curve at around 90° and 270° which can also slightly be seen in the reference curve for the EMA6 this dip can only be seen in the sAB curve ITD and ILD errors of the EMA6 array using different binaural reproduction approaches ITDs and ILDs of the EMA8 array using different binaural reproduction approaches ITD and ILD errors for the EMA8 array using different binaural reproduction approaches both stereo approaches have smaller ITD errors for the glasses array compared to the EMAs BFBR produces errors above the ITD JND for 90° and 270° In the ILD error curve no systematic difference compared to the EMAs can be observed ILDs and ITDs of the glasses array using different binaural reproduction approaches The reference values (black dashed lines) were calculated from the KEMAR HRTFs ITD and ILD errors for the glasses array using different binaural reproduction approaches we analyzed the spectral differences in the form of the averaged differences of the magnitude spectra where bref are the reference binaural signals, and Ωd is the set of Nd directions of the binaural signals (where Ωd is a set of 360 directions in the horizontal plane in steps of 1°). Figure 10 depicts the spectral differences of the EMA6 and shows that Ambisonics and BSM lead to similar differences While Ambisonics performs better near 1 kHz BFBR leads to slightly larger errors than BSM at 1 kHz but performs equivalently at higher frequencies sXY stereo leads to notable differences even at frequencies up to 1.1 kHz which matches the findings from the ILD/ITD figures The largest magnitude errors are at frequencies above 10 kHz for both stereo approaches most probably due to the lack of pinnae cues Figure 11 depicts the average magnitude differences of the binaural signals calculated from the glasses array capture The figure clearly shows that the magnitude differences are higher than for the EMAs the highest errors can be observed for the sXY stereo renderings The magnitude differences of the BSM and the Ambisonics renderings are the lowest The differences of BSM are below 10 dB for almost all frequencies The differences for Ambisonics clearly increase above approximately 16 kHz The figure shows a similar trend as with the EMAs that BSM has larger magnitude differences at lower frequencies compared to Ambisonics but similar or even lower errors at higher frequencies BFBR has larger magnitude errors for nearly all frequencies compared to BSM and Ambisonics the errors of both stereo curves increase at very high frequencies Magnitude differences for the glasses array The quantitative evaluation suggests that BSM and sAB stereo can lead to similar perceptual results to the Ambisonics renderings we conducted two comparative listening experiments Differences in the timbre are related to any differences in coloration Differences in the spaciousness are related to any spatial differences participants rated eight MUSHRA pages in total: EMA6 in the CR1 with the speech signal EMA6 in the CR1 with the drums test signal These factor combinations were repeated for the two metrics We did not set up a complete factorial design with all factor combinations to avoid the experiment being too long participants conducted training consisting of user interface familiarization and signal familiarization 19 participants took part in the experiment Most of whom were staff of the audio group at Reality Labs Research at Meta; none reported any hearing issues The experiment was conducted in remote settings. It was implemented in Matlab and shared with each participant, who conducted the test with their own equipment, i.e., their PC or Mac, audio device, and headphones. We recommended the use of Beyerdynamic DT990 Pro headphones, which where used by 15 participants. According to the choice of headphones, the binaural chain was equalized with appropriate headphone compensation filters provided by Bernschütz et al. (2012) If no headphone filters were available in the database participants were instructed to adjust the volume to a comfortable level that should not change during the experiment All participants were asked to perform the test in a room which was as quiet as possible To evaluate participants’ rating differences between renderings we ranked each rendering within each comparison of stimulus and attribute (by each MUSHRA screen) We then analyzed the ranks for each rendering using a hierarchical multivariate ordinal regression under a Bayesian framework regression models calculate the distribution of parameter estimates as the posterior distribution our model estimated the posterior distribution of each rank for each combination of participant for each Markov-chain Monte Carlo (MCMC) iteration To derive a single estimate of ranking in each independent variable combination we calculated the weighted sum of rankings for each MCMC iteration as follows where p is the expected probability of rank k at each iteration i In order to evaluate ranking differences between renderings we calculated the posterior distribution of differences between rankings for each MCMC iteration for each independent variable combination Ranking difference estimates for which the highest density credible interval does not include zero are considered statistically significant differences All models were constructed using the Stan programming language (Carpenter et al., 2017) through the cmdstan (Gabry and Češnovar, 2021) and brms (Bürkner, 2017, 2018) packages in R statistical computing software (R Core Team, 2021) A graphical overview of the results is presented in Figure 12 in the form of boxplots of the inter-subject variance in the MUSHRA points for each MUSHRA screen and rated attribute separately The plots show that for the timbre attribute (top) most of the ratings are within the range of the Ambisonics rendering An exception is the box for the BFBR results from the EMA6 in reverberant conditions sAB stereo and BSM achieved the highest median ratings They are consequently higher than the median ratings of the Ambisonics renderings The results of the spaciousness attribute (bottom) show that only sAB stereo and BSM were rated similar to or higher than the Ambisonics rendering An interesting observation is that in the reverberant condition BSM was rated significantly better then all other renderings A similar trend is shown in the boxplots for the timbre results in the reverberant condition Comparing the results of the spaciousness attribute for the EMA6 and EMA8 with drums shows that the EMA8 might be favourable for the sAB stereo approach This might be due to the microphone distribution EXPERIMENT 1: Boxplots of the inter-individual variation in the MUSHRA points for each MUSHRA page separately (H) Spaciousness: reverberation EMA6 drums Visual inspection reveals that for the spaciousness attribute Ambisonics N = 4 was ranked higher than BFBR for speech with the EMA6 in dry conditions sAB was ranked higher with the EMA8 in dry conditions and BSM was ranked higher with the EMA6 in reverberant conditions sAB was ranked higher for drums and BSM was ranked higher for both drums and speech Both sAB and BSM were also ranked higher with EMA8 in dry conditions BSM and sXY were ranked higher with EMA6 in the reverberant room BFBR was always ranked in the range of Ambisonics for the timbre attribute EXPERIMENT 1: Median ranks for each rendering by attribute Points represent median rank and error bars depict the 89% highest density credible interval EXPERIMENT 1: Median rank differences between renderings and Ambisonics N =4 by attribute Points represent median rank difference and error bars depict the 89% highest density credible interval Asterisks indicate statistically significant differences The median rank differences (Figure 14) suggests that sAB and BSM perform the best for the EMAs all rendering approaches were rated in a similar range as the N = 4 Ambisonics rendering we employed array impulse responses measured in a room with variable acoustics for two different source positions (loudspeaker one at 23° with a distance of 2 m loudspeaker 2 at 325° with a distance of 1.5 m) We used measurements in dry conditions (RT60 = 0.447 s and in more reverberant conditions (RT60 = 0.564 s The measurements were done with the 6-microphone glasses array described in Section 2.1.2 and for the comparative Ambisonics renderings with an 8-microphone OctoMic array The binaural reference in Experiment 2 was measured with a KEMAR dummy head The test signals were the same as for Experiment 1 such that in total participants again rated eight MUSHRA pages: dry conditions with loudspeaker 1 (spk 1) and the drums signal dry conditions with spk one and speech signal dry conditions with spk 2 and drums signal and the reverberant condition with spk one and the drums signal we only tested a subset of all factor combinations no headphone compensation filters were available for the KEMAR dummy head the second experiment was conducted without any headphone equalization and data analysis were identical to Experiment 1 A graphical overview of the results is presented in Figure 15 in the form of boxplots of the inter-subject variance in the MUSHRA points for each MUSHRA page and the timbre and spaciousness attributes the glasses array is the more challenging condition except for the results of the BSM renderings for spk 2 all timbre ratings are within the range of the Ambisonics results BFBR and sAB seem to perform the best regarding the timbre the boxplots do not indicate any approach as being the best Only the results for sXY stereo for spk 2 are notably worse compared to the other conditions EXPERIMENT 2: Boxplots of the inter-individual variation in the MUSHRA points for each MUSHRA page separately (H) Spaciousness: reverberation spk1 drums Median ranks for each rendering and test signal, together with 89% credible intervals, are shown in Figure 16 EXPERIMENT 2: Median ranks for each rendering by attribute To investigate how the approaches performed compared to the Ambisonics renderings Figure 17 shows the median rank differences between each rendering approach and Ambisonics N = 2 together with 89% credible intervals and asterisks indicating statistically significant differences Ambisonics N = 2 was ranked higher than sXY for spk 2 in dry conditions BFBR was ranked higher for speech with spk one in dry conditions and for drums with spk one in reverberant conditions Ambisonics N = 2 was ranked higher than BSM with spk 2 in dry conditions Median rank differences suggest that in most cases all renderings were rated similar to the Ambisonics rendering EXPERIMENT 2: Median rank differences between renderings and Ambisonics N =2 by attribute Points represent median rank differences and error bars depict the 89% highest density credible interval A primary motivation of the study was to investigate if capture from non-spherical arrays can lead to auralization that is comparable to the established Ambisonics chain Both quantitative and perceptual evaluation suggest that for EMAs with six and eight microphones sAB stereo and BSM performed comparably to the fourth-order Ambisonics reproduction of SMA capture with an Eigenmike sampling scheme considering the increased microphone count 32) of the Eigenmike compared to the EMA6 and EMA8 For the glasses array with six microphones BFBR and sAB stereo performed comparably only to a second-order Ambisonics reproduction of SMA capture with an OctoMic the glasses array is certainly the more challenging array configuration; that is also supported by the quantitative evaluation It can be assumed that sAB stereo highly depends on the location of the microphones; this is supported by the ITD and ILD analyses The results of the EMA experiment show that regarding the spaciousness microphones at ϕ = 90° and ϕ = 270° might be advantageous the timbre is not affected by the microphone position we could not find any significant difference in the performance of sAB stereo between the EMAs and the glasses array The listening experiment results show that sXY reproduces the sound scene with a relatively accurate timbre sXY stereo does not lead to good spatial reproduction This strongly matches the findings from the quantitative evaluation sXY cannot restore the correct ITDs and ILDs for one thing due to collocation of the beams and for another due to non-optimal beamforming MD beamforming with a small number of microphones introduces side lobes which might cause the ITD and ILD distortions the original XY stereophony employs microphones with cardioid directivity instead of maximum directivity BFBR was rated better for the glasses array than for the EMAs; the quantitative evaluation does not clearly supported this BFBR has larger magnitude differences for the glasses array than for the EMAs compared to BSM or Ambisonics It might be due to the inconsistent use of the rating scale Another explanation could be that for the EMAs all microphones are in the horizontal plane This does not affect the ITD and ILD analysis since we only considered horizontal sound incidences but may affect complex sound scenes the source distance was 2.4 and 6 m; for the glasses array 1.5 and 2 m This might further influence the performance of BFBR it is interesting to mention that BSM behaves in the opposite way; it was rated better for the EMAs Madmoni et al. (2021) investigated the influence of the microphone distribution on the performance of BSM they only investigated semi-circular array configurations They concluded that for static reproduction microphones placed close to the ears are favourable uniformly sampling on a full-circular array has advantages Our study did not find any significant difference between the EMA6 and EMA8 Future work is suggested to develop design criteria for optimal array configurations for the BSM method which interpolates between neighboured microphone signals according to the listeners’ head orientation The significant advantage of sXY stereo is its simplicity; it does not require HRTF processing sXY stereo does not necessarily require microphones at the position of the listener’s ears Binaural signals for different head orientations could be synthesized by varying the directions of the XY beams The clear benefit of BFBR is that it is the most flexible approach Since the sound field is decomposed into different directional components This could be used to either synthesize different head orientations or amplify specific directions of the sound field different HRTFs can easily be integrated since they are not incorporated in the beamforming coefficients beamforming plays an important role in consumer devices for applications that enhance speech intelligibility BSM seems to reproduce the most accurate binaural signals the BSM filters already incorporate the HRTFs which is why a complete set of BSM filters is required for each head orientation applying dynamic binaural synthesis would require a large set of beamforming coefficients This study only focuses on scene-based approaches, i.e., re-synthesis of the entire captured scene. In future work, it would also be conceivable to apply parametric approaches, like DiraC (Pulkki, 2007) or SIRR (Merimaa and Pulkki, 2004) objects or specific dominant sound sources of the sound field could be extracted and spatially rendered We presented a comparison of approaches for the binaural rendering of capture from equatorial microphone arrays and capture from a glasses microphone array A MUSHRA-like listening experiment applying non-head-tracked binaural synthesis showed that the approaches have potential to synthesize spatial sound scenes with similar quality as Ambisonics renderings from spherical microphone array capture with a similar number of microphones Beamforming-based binaural reproduction with binaural signal matching and a microphone-based stereo approach performed the best for equatorial arrays beamforming-based binaural reproduction and microphone-based stereo performed the best The results further suggest that for non-head-tracked binaural reproduction the more sophisticated beamforming approaches (BSM or BFBR) do not outperform the simple microphone-based stereo approach Future work is suggested to investigate how the approaches perform with head-tracked dynamic binaural reproduction we only focused on sound sources in the horizontal plane The performance of the approaches with elevated sound sources or vertical head movements needs to be investigated in future work The raw data supporting the conclusions of this article will be made available by the authors The studies involving human participants were reviewed and approved by an internal research review committee and an external institutional review board (IRB) Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements implemented or maintained the tested algorithms He also wrote the first draft of manuscript and PC assisted in refining the research question and experimental design JC designed and performed the statistical analysis All authors contributed to manuscript revision and read and approved the submitted version This work was done during an internship with Reality Labs Research at Meta The authors would like to thank Lior Madmoni and Boaz Rafaely for providing us with the code of BSM as well as our collegues from Reality Labs - Research and Andrew Luck who greatly assisted in this internship project Many thanks also to all voluntary participants The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher *also at Institute of Communications Engineering TH Köln - University of Applied Sciences 1Throughout this article 2https://www.vvaudio.com/landing/VVOctoEncode_OctoMic. 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The use distribution or reproduction in other forums is permitted provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited in accordance with accepted academic practice distribution or reproduction is permitted which does not comply with these terms *Correspondence: Tim Lübeck, dGltLmx1ZWJlY2tAdGgta29lbG4uZGU= Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish he could have ended up designing rockets for Boeing or making any number of other scientific contributions Georg Luebeck wound up at Fred Hutchinson Cancer Center his mathematical models of biological processes like cancer initiation and growth have helped everyone from uranium miners at risk for lung cancer to astronauts facing the effects of galactic cosmic radiation Or is it 33?” Luebeck said of his time at the Hutch “So much of the research and the methods and the technologies have changed whole-genome sequencing and array technologies to interrogate genomes down to the single-cell level.” there is much more data — clouds full of it — and an even greater need to make sure it’s all interpreted in ways that make sense That’s where Luebeck’s mathematical modeling of multi-stage carcinogenesis comes in “It’s important to have an intellectual context in which you can explain your data,” he said you can easily be led astray and misinterpret the data.” Luebeck earned his doctorate in theoretical physics at the University of Washington and went on to do postdoctoral work at the Neils Bohr Institute for Astronomy Physics and Geophysics in Copenhagen before returning to Seattle and joining the Hutch Luebeck still remembers meeting his mentor-to-be during that first job interview and he pulled out two research papers from a huge stack and suggested my reading them,” Luebeck said genetics and biostatistics were new to him then He soon was able to assist his mentor Moolgavkar and began working in lung cancer with former Hutch radiation biophysicist Dr investigating the association between lung cancer and radon exposure “There was a public health concern of radon in homes and in the population of uranium miners,” he said was much less of a ‘cancer initiator’ — a long-held dogma — and much more of a ‘cancer promotor,’ increasing the growth of bad lesions.” He and Moolgavkar used data from several studies to develop new lung cancer risk models The approach they used “assumed a series of biological processes that we modeled computationally and mathematically,” he said “It was a new way of modeling risks from environmental exposures such as radon.” Luebeck and Moolgavkar were joined by others across the world interested in radiation carcinogenesis in particular modeling cancer risks among A-bomb survivors “It became clear that the biological cancer models we developed had wider applications including cancer sites such as colon trying to understand how long it takes for cancers and their precursors to develop that he first became interested in the concept of tissue aging “The idea that tissue aging somehow also plays a role in the initiation of a cancer was something that clicked with me,” he said Luebeck and his colleagues were able to bring mathematical models to this area by looking at the age of the tissue and backtracking to when a cancer and its precursor first arose “We were able to use statistical approaches to turn this information into a molecular clock,” he said “When you find an adenoma in colon screening How old is it?’ Colorectal cancers presumably arise in adenoma but when did the adenoma (the one that makes the cancer) first arise That’s the question that’s hard to investigate Luebeck created a cancer model that showed that a founder premalignant cell that goes on to become cancerous can actually develop in the first decade of life The paper, published in 2019 in the journal Cancer Research found that precancerous lesions ”can persist for decades before becoming cancerous,” data that suggests that “early dietary and lifestyle interventions may be more effective than later changes in reducing colorectal cancer incidence,” the authors wrote Can that information somehow be used to improve colon screening “We could start thinking about chemoprevention [taking cancer-preventive drugs] that detect the precursors in which malignancies arise,” he said Luebeck’s modeling and molecular clocks are considered for use in other cancers Over the last ten years, in collaboration with Fred Hutch physician-scientist Dr. Bill Grady and former graduate student Kit Curtius (now at UC San Diego) Luebeck created a DNA methylation clock for esophageal cancers that arise as a result of the condition Barrett’s esophagus But the critical information nobody was able to provide was: How long has this tissue been in place?” BE starts with injury to the tissue by acid reflux But many people don’t know if they have BE “Reflux or bile juices cause erosion in the lower esophagus and the tissue can turn into metaplasia [sometimes a precursor to cancer],” he said “Roughly half the people who get esophageal cancers never had GERD symptoms.” Only a fraction of people with BE actually go on to develop esophageal adenocarcinoma or EAC (about 5%) So those who are diagnosed with it are at risk of overdiagnosis and possibly overtreatment while some of those who are not may develop EAC without a chance of an intervention “Does age really matter as a risk factor for cancer “There’s a clear correlation between age and cancer risk the more stem cell divisions and the higher the number of mutational events that lead to cancer Since many people who develop EAC have no symptoms from Barrett’s esophagus Preventive Services Task Force doesn’t currently offer any kind of screening guidelines for it Luebeck also hopes this work will enable clinicians to find a way to identify those at risk Luebeck’s desire to continue clocking cancer — and collaborate with others at the Hutch determined to do the same — have kept him intrigued and engaged for more than three decades years in which he’s seen “mind-boggling” progress in cancer research and technology the most enjoyable thing is the interaction with other people at the Hutch just being exposed to ideas and the teamwork that comes from it People have different strengths — in computer modeling or computer programming or in the medical field or genetics — we bring all these together.” Fred Hutchinson Cancer Center is an independent organization that serves as UW Medicine's cancer program © 2025 Fred Hutchinson Cancer Center, a 501(c)(3) nonprofit organization 1100 Fairview Ave. N., P.O. Box 19024, Seattle, WA 98109-1024 206.667.5000Contact Us Metrics details it is unclear whether ecDNA is a later manifestation of genomic instability or whether it can be an early event in the transition from dysplasia to cancer to better understand the development of ecDNA we analysed whole-genome sequencing (WGS) data from patients with oesophageal adenocarcinoma (EAC) or Barrett’s oesophagus These data included 206 biopsies in Barrett’s oesophagus surveillance and EAC cohorts from Cambridge University We also analysed WGS and histology data from biopsies that were collected across multiple regions at 2 time points from 80 patients in a case–control study at the Fred Hutchinson Cancer Center the frequency of ecDNA increased between Barrett’s-oesophagus-associated early-stage (24%) and late-stage (43%) EAC suggesting that ecDNA is formed during cancer progression In the cohort from the Fred Hutchinson Cancer Center 33% of patients who developed EAC had at least one oesophageal biopsy with ecDNA before or at the diagnosis of EAC In biopsies that were collected before cancer diagnosis higher levels of ecDNA were present in samples from patients who later developed EAC than in samples from those who did not We found that ecDNAs contained diverse collections of oncogenes and immunomodulatory genes ecDNAs showed increases in copy number and structural complexity at more advanced stages of disease Our findings show that ecDNA can develop early in the transition from high-grade dysplasia to cancer and that ecDNAs progressively form and evolve under positive selection Two surveillance studies of patients with Barrett’s oesophagus including a longitudinal case–control study with multi-regional WGS sampling provided us with an opportunity to study the role of ecDNA in the transition from Barrett’s oesophagus to EAC Breakdown of the histological disease states among patients with Barrett’s oesophagus in the Cambridge selected cross-sectional study representing the highest disease state for that patient The FHCC cohort consisted of 80 patients for whom biopsies were collected prospectively The cohort was separated later into two groups of 40 patients who had cancer outcomes (CO) and non-cancer outcomes (NCO) Sample collection at time points TP-1 and TP-2 for sequencing biopsies and histology biopsies Two sequencing biopsies were collected at each time point ethylenediaminetetraacetic acid (EDTA) application and microdissection were performed to isolate Barrett’s oesophagus (BE) tissue and improve purity for sequencing Highlighted box indicates isolated Barrett’s oesophagus tissue (box width indicates approximately 50 µm) WGS biopsies and histology biopsies were collected independently Some histology and sequencing biopsies were taken at the same level of the oesophagus (on-level) and some histology biopsies fell within a ±1-cm window of the measured height of the sequencing biopsy (windowed histology) Experimental workflow for analysing the WGS samples A brief overview of the process by which biopsies were selected sequenced and characterized by AmpliconArchitect Characterization of the ecDNA status and cancer stage of patient samples from the Cambridge cohorts of patients with early- and late-stage EAC Comparison of the ecDNA status and histological group of samples reveals an association between ecDNA and early-stage EAC The odds ratio (OR) and the confidence interval (CI) of the OR are shown Characterization of the ecDNA status and on-level histology of samples collected for FHCC CO patients across time points TP-1 and TP-2 for the two oesophageal sequencing samples (‘upper’ and ‘lower’) The maximum histology of any biopsy from that time point is also shown Asterisk indicates cancer diagnosis made at next endoscopy (1.44 and 8.16 months after TP-2 for patients 568 and 772 Comparison of ecDNA status in any FHCC patient sample and cancer-outcome status among patients reveals an association between ecDNA and cancer outcome the proportion of TP-1 samples without HGD or EAC in on-level histology (having Barrett’s oesophagus or LGD) versus with HGD in the on-level histology shows an enrichment for ecDNA with advanced disease status (Fisher’s exact test the proportion of TP-2 samples without EAC in on-level histology (having HGD or Barrett’s oesophagus) versus with EAC in on-level histology shows an association between ecDNA and the development of EAC (Fisher’s exact test the patient died of causes unrelated to Barrett’s oesophagus 2.84 years after TP-2 showing a highly significant association between ecDNA in Barrett’s oesophagus biopsies and progression to EAC (Fisher’s exact test HGD was treated immediately after detection so it was not possible to determine whether the HGD samples would subsequently have progressed to cancer All eight FHCC samples in which ecDNA was found before cancer diagnosis (TP-1) showed biallelic disruption of TP53 The appearance of ecDNA as a subset of TP53-altered cases suggests that the prior loss of TP53 enables ecDNA formation indicating that there are other mechanisms of ecDNA formation after TP53 alteration Timeline of sample collection for FHCC CO patient 391 relative to patient age Summary of the ecDNA status and windowed-histology status for four endoscopies with the time interval between each indicated The distance of the biopsy from the gastro-oesophageal junction (GEJ) is also shown The two resection samples are labelled as E8 and C5 Two distinct species of ecDNA are labelled as ecDNA-1 and ecDNA-2 Inferred phylogeny of Barrett’s oesophagus samples from patient 391 across the four endoscopies with branching reporting the ecDNA formation events annotated by the histological status of the sample (windowed) in which EAC was diagnosed and present within ±1 cm ecDNAs detected in pre-cancer are frequently maintained through the transition to cancer and genomically overlapping ecDNAs identified from multi-region sampling are likely to have a common origin these data suggest that ecDNA can be a truncal event in the formation and evolution of EAC Proportion of patients with ecDNA detected in any sample across all study cohorts Maximum genomic copy number (CN) of ecDNA segments in pre-cancer samples and EAC (or EAC-linked for FHCC) samples Complexity score of focally amplified ecDNA-positive genomic regions for pre-cancer and EAC samples For ecDNAs identified across multiple FHCC samples that were determined to be clonal on the basis of amplicon similarity the increase in ecDNA copy number for each pair of clonal ecDNAs separated by the difference in associated histology of the two samples shows an association between increasing copy number and increasing histological severity Comparative overlap of Barrett’s-oesophagus-associated oncogenes found on ecDNA in the four cohorts For oncogenes recurrently detected on ecDNA in samples from different patients the number of patients with a sample that has the listed oncogene included on ecDNA Oncogene copy number for the focally amplified oncogene with the highest copy number on each unique focal amplification (ecDNA or non-ecDNA fsCNA) is significantly higher on ecDNA versus non-ecDNA fsCNA raising the possibility that tumours might achieve subclonal ecDNA heterogeneity early on and that competition between multiple distinct ecDNAs could have a role in the evolution of EAC ecDNAs contained 0.76 unique oncogenes per amplicon (97 oncogenes in 127 ecDNAs) compared to 0.52 (192/373) unique oncogenes per amplicon in non-extrachromosomal focal somatic copy number amplifications (fsCNAs) suggesting that ecDNA may allow a wider variety of oncogene amplifications suggesting that—despite the high diversity of ecDNA-borne oncogenes—ecDNAs are positively selected in a manner that is specific to cancer type It has been unclear whether ecDNA can contribute to the transformation of pre-cancer to cancer or whether it is a later manifestation of tumour genomic instability in multiple cohorts of patients with Barrett’s oesophagus and that its presence is strongly associated with EAC progression ecDNA amplifies a broader range of oncogenes and their copy numbers increase rapidly and markedly in EAC Increased ecDNA heterogeneity may also enhance adaptation to changing conditions the clonal selection and maintenance of immunomodulatory genes on ecDNA before cancer development could aid immune evasion these results indicate that ecDNA contributes to the development of cancer through several mechanisms These findings shed light on how ecDNA can arise before the development of full-blown cancer indicating that it is not simply a late manifestation of genome instability and raise the possibility of earlier intervention or prevention for patients with ecDNA-containing tumours The significance of odds ratios and differences in event frequencies between groups were assessed by Fisher’s exact test The default test type was two-sided in statistical tests the box limits are the upper and lower quartiles and the whiskers are 1.5 times the interquartile range or represent minimum or maximum values if there are no outliers Patients with low-grade Barrett’s oesophagus and high-grade Barrett’s oesophagus underwent surveillance at Cambridge University Hospitals NHS Trust and consented prospectively to a biomarker and genomic characterization study (Cell Determinants Biomarker Strict selection criteria were implemented to ensure that only the highest-cellularity biopsies Potential biopsies were placed into optimal cutting temperature compound and a single section was cut and stained with haematoxylin and eosin (H&E) These were reviewed by at least two consultant pathologists to assess the composition of the biopsy All pathologists were blinded to the grade of the patient Samples with no agreement were reviewed by a third pathologist to reach a consensus Dysplastic samples for sequencing had to have a pathological cellularity for dysplasia of at least 30% and were labelled to be consistent with the highest pathology grade reported within the biopsy (tumour cellularity of 70% or higher for early-stage cancers) Non-dysplastic Barrett’s oesophagus biopsies had to contain intestinal metaplasia Barrett’s oesophagus research samples were collected at every 2 cm of the Barrett’s oesophagus segment at endoscopy A snap-frozen section was taken from each Barrett’s oesophagus sample to determine the grade of dysplasia Patients in the pre-cancer categories who received previous ablative treatment were excluded Samples with squamous contamination were excluded Genomic regions with a total copy number greater than 4.5 and an interval size greater than 10 kbp were identified merged and refined with the amplified_intervals.py script Each seed region was given to AmpliconArchitect separately to improve runtime on each sample AmpliconArchitect was run in the default explore mode to reconstruct amplicon structures and amplicons formed by the same regions were deduplicated on the basis of genomic overlap such that for overlapping AmpliconArchitect amplicons the amplicon with the highest-level classification was kept (ranked by ecDNA with ties being broken by largest amplicon size which provides a cloud-based platform for TCGA data analysis AmpliconClassifier also specified BED files corresponding to the classified regions and annotated the identity of genes on the focal amplifications If a sequencing biopsy had a histology biopsy from the same level along the oesophagus (measured from the gastro-oesophageal junction) then it was denoted as having on-level histology If a sequencing biopsy had a histology biopsy from within ±1 cm of the same level it was denoted as having windowed histology When multiple histology samples could be paired with the sequencing the histology biopsy with the most severe disease state was assigned Alteration was defined as one or more copies of TP53 being affected by a mutational event When evaluating the presence of genes on ecDNA the average gene copy number was required to be 4.5 or higher and the 5′ end intact Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity Targeted therapy resistance mediated by dynamic regulation of extrachromosomal mutant EGFR DNA Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers Extrachromosomal oncogene amplification in tumour pathogenesis and evolution Extrachromosomal DNA: an emerging hallmark in human cancer The evolutionary dynamics of extrachromosomal DNA in human cancers Predictors of progression in Barrett’s esophagus: current knowledge and future directions Predictors of dysplastic and neoplastic progression of Barrett’s esophagus Temporal and spatial evolution of somatic chromosomal alterations: a case-cohort study of Barrett’s esophagus Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis Genomic copy number predicts esophageal cancer years before transformation Multi-omic cross-sectional cohort study of pre-malignant Barrett’s esophagus reveals early structural variation and retrotransposon activity Somatic whole genome dynamics of precancer in Barrett’s esophagus reveals features associated with disease progression ecDNA hubs drive cooperative intermolecular oncogene expression Live-cell imaging shows uneven segregation of extrachromosomal DNA elements and transcriptionally active extrachromosomal DNA hubs in cancer Circular ecDNA promotes accessible chromatin and high oncogene expression Functional enhancers shape extrachromosomal oncogene amplifications Exploring the landscape of focal amplifications in cancer using AmpliconArchitect Distinct classes of complex structural variation uncovered across thousands of cancer genome graphs Unscrambling cancer genomes via integrated analysis of structural variation and copy number Rearrangement processes and structural variations show evidence of selection in oesophageal adenocarcinomas Stachler, M. D. et al. Genomic signatures of past and present chromosomal instability in the evolution of Barrett’s esophagus to esophageal adenocarcinoma. Preprint at bioRxiv https://doi.org/10.1101/2021.03.26.437288 (2023) 8th edition AJCC/UICC staging of cancers of the esophagus and esophagogastric junction: application to clinical practice The Cancer Genome Atlas Research Network.Integrated genomic characterization of oesophageal carcinoma Links between mutant p53 and genomic instability Chromothripsis drives the evolution of gene amplification in cancer Chromothripsis followed by circular recombination drives oncogene amplification in human cancer Chromosome segregation errors generate a diverse spectrum of simple and complex genomic rearrangements Tolerance of whole-genome doubling propagates chromosomal instability and accelerates cancer genome evolution Massive genomic rearrangement acquired in a single catastrophic event during cancer development Mechanisms generating cancer genome complexity from a single cell division error Immunohistologic analysis of the inflammatory infiltrates associated with osseointegrated implants Functional genomic landscape of cancer-intrinsic evasion of killing by T cells NLRC5: a key regulator of MHC class I-dependent immune responses MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers RMI2 plays crucial roles in growth and metastasis of lung cancer Evolutionary dynamics in Barrett oesophagus: implications for surveillance Characterizing the ecological and evolutionary dynamics of cancer Computing the statistical significance of overlap between genome annotations with iStat Clonal heterogeneity and tumor evolution: past Abnormal TP53 predicts risk of progression in patients with Barrett’s esophagus regardless of a diagnosis of dysplasia Ordered and deterministic cancer genome evolution after p53 loss CNVkit: genome-wide copy number detection and visualization from targeted DNA sequencing Allele-specific copy number analysis of tumors SciPy 1.0: fundamental algorithms for scientific computing in Python The mean and variance of the moments of chi-squared when used as a test of homogeneity Li, H. Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. Preprint at arXiv https://doi.org/10.48550/arXiv.1303.3997 (2013) A framework for variation discovery and genotyping using next-generation DNA sequencing data A program for annotating and predicting the effects of single nucleotide polymorphisms Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration Strelka2: fast and accurate calling of germline and somatic variants ONGene: a literature-based database for human oncogenes The landscape of selection in 551 esophageal adenocarcinomas defines genomic biomarkers for the clinic Paired exome analysis of Barrett’s esophagus and adenocarcinoma HisgAtlas 1.0: a human immunosuppression gene database Download references Department of Computer Science and Engineering Bioinformatics and Systems Biology Graduate Program Divisions of Human Biology and Public Health Sciences Department of Biopharmaceutical Convergence Department of Biohealth Regulatory Science Department of Cellular and Molecular Medicine The Jackson Laboratory for Genomic Medicine Children’s Medical Center Research Institute University of Texas Southwestern Medical Center and Medicine for Human Health (Sarafan ChEM-H) led the Cambridge University UK team and T.G.P Computational methods introduced in the manuscript were conceived by J.L provided input during the writing of the paper All authors provided feedback on the analyses chairs the scientific advisory board (SAB) of and has equity interest in Boundless Bio is also an advisor with equity for Asteroid Therapeutics and is an advisor to Sage Therapeutics SAB member and has equity interest in Boundless Bio and Abterra and the terms of this arrangement have been reviewed and approved by the University of California San Diego in accordance with its conflict of interest policies is a member of the SAB of Dimension Genomics is named on patents related to Cytosponge and associated assays that were licensed to Covidien (now Medtronic) is a co-founder of Boundless Bio and an advisor to Stellanova Therapeutics and NeuroTrials is a compensated consultant and has equity interest in io9 His spouse is an employee of Biotheranostics is an inventor on the US patent 10,776,718 for source identification by non-negative matrix factorization also declares provisional patent applications for ‘Clustered mutations for the treatment of cancer’ (US provisional application serial number 63/289,601) and ‘Artificial intelligence architecture for predicting cancer biomarker’ (serial number 63/269,033) and also declares a provisional patent application for ‘Methods and biomarkers in cancer’ (US provisional application serial number 114198-1160) is a part-time paid consultant for Boundless Bio declare a patent application related to this work: ‘Methods and compositions for detecting ecDNA’ (US patent application number 17/746,748) The remaining authors declare no competing interests Nature thanks Lorenzo Ferri, David Wang and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Oncoprint table for samples from Cambridge patient with Barrett’s oesophagus and EAC segregated by histology type showing ecDNA status histology or cancer stage (if applicable) TP53 alteration (by mutational analysis non-ecDNA) status and prior therapy (chemotherapy or radiation) on the tumours in patients with cancer Proportion of Cambridge EAC tumour samples with ecDNA separated by tumour stage I versus stage II or higher Oncoprint tables of samples from FHCC CO patient WGS samples encoding ecDNA status TP53 alteration (at least one gene copy affected) as well as on-level and windowed histology for each time point and both upper and lower oesophageal samples for time points TP-1 and TP-2 Maximum histology from any histology biopsy is shown at the bottom of each time point Asterisk indicates cancer diagnosis made at next endoscopy since biopsies from the diagnostic EAC endoscopy were unavailable for CO patient ID 772 and lacked sufficient DNA for CO patient ID 568 so biopsies from the penultimate endoscopy were substituted (occurring 1.44 and 8.16 months after TP-2 for patients 568 and 772 Oncoprint tables of FHCC NCO patient WGS samples encoding ecDNA status Oncoprint tables of biopsies from NCO patients from the FHCC cohort with long-term follow-ups (in orange Distribution of FHCC NCO follow-up durations from TP-2 to the time at which the patient was last known to be alive (top mean = 13.9 years) or TP-2 to death (bottom Association of ecDNA presence and TP53 status in biopsies from patients from the FHCC cohort Association of ecDNA presence and TP53 status in samples from patients from the Cambridge cohort Proportion of FHCC samples with WGD separated by TP53 alteration status Proportion of FHCC samples with chromothripsis separated by TP53 alteration status Proportion of TP53 alteration FHCC samples with ecDNA All statistical differences in frequencies were assessed by one-sided Fisher’s exact test Barrett’s oesophagus segment samples from patient 391 show conserved focal amplification of BFB and emergence of ecDNA between time points TP-1 and TP-2 The structure of ecDNA-1 detected in the lower pre-cancer sample from TP-2 in patient 391 and an identical structure derived from the adenocarcinoma resection detected in the upper sample from TP-2 in patient 391 in which EAC was present in the histology window Amplicon similarity analysis of ecDNA-1 and -2 reveals common origins of the structures The length of predicted genomic intervals captured on ecDNA for each distinct ecDNA in the combined cohorts compared by pre-cancer versus EAC (Mann–Whitney U test For oncogenes detected on ecDNA in samples from at least one patient the number of patients with at least one sample having the oncogene listed on ecDNA and the frequency of that gene on other types of focal amplifications Proportion of the set of possible unique genes on ecDNA Difference assessed by one-sided Fisher’s exact test Distribution of the number of oncogenes on individual ecDNA For immunomodulatory-associated genes detected on ecDNA the number of patients with at least one sample having the gene listed on ecDNA and the frequency of that gene on other focal amplifications as well Copy number for the highest copy number focally amplified immunomodulatory-associated gene in each unique amplicon that was ecDNA or non-ecDNA fsCNA ecDNAs show a significantly higher copy number of immunomodulatory-associated genes on ecDNA versus non-ecDNA fsCNA (Mann–Whitney U test This file contains Supplementary Methods and Supplementary Figures 1-4 This file contains sample metadata and histology labels This file contains FHCC patient age at sampling and additional histology labels This file contains focal amplification classifications for all samples in the study This file contains properties related to the sample purity coverage for the FHCC and Cambridge samples This file contains focal amplification similarity scores for ecDNAs This file contains genes carried on all focal amplifications This file contains a list of immunomodulatory genes used in this study This file contains a list of oncogenes used in this study Download citation DOI: https://doi.org/10.1038/s41586-023-05937-5 Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research UK-based midstream LNG & bio-LNG company Avenir LNG has conducted its first ship-to-ship (STS) LNG bunkering operation in Germany in the Port of Lübeck for ferry owner and operator TT-Line Avenir teamed up with German LNG & bio-LNG distribution company GasCom-Equipment “I am pleased to see how efficiently and smoothly the joint preparations and the execution of the bunker operation were done The cooperation proved again how important coupling expertise from different specialists is for establishing supply infrastructure for alternative fuels in German ports We are glad to be part of that and are looking forward to more jointly executed bunker operations in the future,” said Norbert Scholz After an initial LNG & bio-LNG bunker operation conducted with trucks by Avenir in 2022 this event marked another milestone as the first STS LNG bunker operation in a German port the company revealed in a social media update Commercial Director of LNG Bunkering for Avenir stated: “Our first successful STS bunker operation in a German port for our long-standing and trusted customer TT-Line proves again our leading position in setting up alternative fuel supply chains Utilizing our fleet of five LNG bunker vessels Avenir continues to ensure the security of supply for our customers globally we are seeing our network of customers and ports to service continuing to grow across Northwest Europe throughout 2024.” The UK-based company recently placed an order for two 20,000 cbm LNG bunker and supply vessels at China’s Nantong CIMC Sinopacific Offshore & Engineering (SOE) in China The new investment program marks the second phase of growth for the company increasing the fleet by 40% and 80% in terms of total capacity Daily news and in-depth stories in your inbox Ingersoll Rand Engineering Project Solutions At Ingersoll Rand’s Engineering Project Solutions we have been managing and implementing engineered to-order air packages for complex technical requirements for over 60 years We provide specialized custom compressed air and gas compressors as well as nitrogen generation packages to international EPC contractors and engineering companies across a range of […] Share on FacebookShare on X (formerly Twitter)Share on PinterestShare on LinkedInEAU CLAIRE (WEAU) - Eau Claire police say Maxwell Luebeck has been taken into custody by the Wisconsin State Patrol on Highway 53 near Superior Court records show Luebeck is charged with armed robbery EAU CLAIRE, Wis. (WEAU) - Eau Claire police are naming the suspect in the robbery of WESTconsin Credit Union. According to the Eau Claire Police Department the suspect from the armed robbery at WESTconsin Credit Union has been identified as 25-year-old Maxwell Luebeck A search warrant was served at Luebeck’s home Eau Claire Police say Luebeck is believed to be driving a blue/green 2009 Hyundai Tucson Sport Utility- WI License Plate-ARJ 7875 It is believed Luebeck’s vehicle was seen in the area of Ashland The Eau Claire Police Department describes Luebeck as “a while male Luebeck should be considered armed and should not be approached anyone with information on Luebeck’s location should contact local law enforcement immediately They were protesting the undervaluation of their work and at home; calling for their voices to count; and objecting to being excluded from important parts of society An amazing 90 percent of Iceland’s female population took part in the mass action ensuring that the day would go down in history.This documentary gives a chance for those erstwhile protestors to speak using their words and vivid archival footage to depict how a simple idea became a revolution – today Iceland is one of the leading countries in the world for gender equality The film creates an arresting memorial to the brave and funny women whose actions triggered that progress We use external content from third-party providers such as video streaming services. By activating this content, personal data may be collected from you. Consent to activation is voluntary and can be revoked at any time. These cookies allow us to understand how visitors behave on our website, e.g. how long they stay on a page on average, whether and how often they return. This allows us to keep improving our website. Our editors will review what you’ve submitted and determine whether to revise the article. Critical Conversations: bridging pathways forward to greater understanding and creative solutions “Carlebach Küchentuch #5” (2015) English translation: In the town hall near the synagogue where Salomon Carlebach was Rabbi from 1870 to 1919 Felix Carlebach and his family are honored by the people of Lübeck (from Nachbarn: Neighbors in a German Town) a solo exhibition by Pratt alumnus Ken Aptekar (M.F.A Annen Museum in the city of Lübeck in northern Germany which is the German word for “neighbors,” draws from Lübeck’s long and complicated multicultural history to explore themes of tolerance and “otherness.” Aptekar was commissioned by the museum to create the exhibition Aptekar and the exhibition have garnered media attention in a number of outlets including a feature in The Guardian and coverage on German national public television Lübeck serves as the focal point for the broader themes and tensions explored in the exhibition which had lived alongside Christians for centuries and Turkish Muslims now have a significant presence there adding to the diversity of the town’s population the atmosphere in Lübeck has remained charged with several terrorist attacks targeting the Lübeck synagogue in the past two decades and anti-Muslim immigrant demonstrations on the rise whose art often combines painting with text to consider Lübeck’s cultural history and Christian Lübeckers’ attitudes towards the Muslims and Russian Jews now living there Aptekar incorporated images from the museum’s famed collection of medieval Christian altarpieces and overlaid them with text elements offering new messages from one neighbor to another utilizing art history to highlight themes that have particular relevance in Europe and around the world today “I’ve observed a frightening rise in violent responses to otherness Living in both Paris and New York has heightened my sense of urgency to respond to the Paris attacks of November 13 and Charlie Hebdo and to the hateful rhetoric of politicians who exploit fear of others to grab power,” said Aptekar “I saw in the history of this town in Germany a great opportunity for art to spark conversations across the cultural divide My hope is that the exhibition will encourage peaceful and rewarding exchanges with our neighbors Aptekar received grants from the Memorial Foundation for Jewish Culture and the New York Foundation for the Arts/Artspire/Malka Fund to create the works on view at St whose presentation was supported by the Possehl Stiftung in Lübeck He has also created commissioned works for museums including the Corcoran Museum in Washington D.C.; the Victoria and Albert Museum in London; and the Musée Robert Dubois-Corneau in Brunoy The story in The Guardian can be found here. It’s Lübeck’s main landmark, and in addition, a structure so famous that it was stamped on two-euro coins in 2006. The Holsten Gate was built in the 15th century to protect the city against foreign conquest. Nowadays its walls, some of which are up to 3.50 meters thick, enclose a museum detailing the city’s history. Lübeck’s Old Town boasts many elaborately ornamented brick buildings - like the Burgtor, the northern city gate, with the customs house. The entire Old Town has been a UNESCO World Heritage site since 1987. The use of baked red bricks as building materials arrived in northern Europe in the 12th century. It led to the emergence of the northern German Brick Gothic architectural style. Seafaring and trade made Lübeck rich in the Middle Ages. More and more people flocked to the city, but space on the Old Town island was limited, so courtyards behind the main buildings were built up. Small, two story buildings and narrow lanes resulted. Nowadays, small alleys still lead from the main streets into the jumble of the courtyards — ideal places to explore! Lübeck’s ship’s captains used to meet here. The Schiffergesellschaft is the former seafarers‘ guild house. Nowadays the gabled building, which dates from 1535, houses a restaurant with a maritime theme. Regional cuisine is served. Of course, that includes seafood dishes in many variations. This sweetmeat made of almonds and sugar originated in the Orient, but it has a long tradition in Lübeck. Here confectioners always had the ingredients to hand, because the city was an important commercial center. Goods from around the world were available here. To this day, Lübeck is famed for its marzipan. At the young age of 22, Thomas Mann wrote “Buddenbrooks,” about the rise and fall of a Lübeck merchant’s family. Later the writer was awarded the Nobel Prize in literature for the work. A museum in Lübeck is devoted to him: the Buddenbrookhaus is furnished as a setting for his novel. Lübeck is considered the "queen of the Hanseatic League”. In the Middle Ages the city played a major role in organizing the northern German merchants’ confederation. It’s no wonder, then, that in 2015 the European Hanseatic League Museum was opened in Lübeck. Specially decorated rooms illustrate the way life was lived at the time the League flourished. What was good for the Hanseatic League merchants is still good for Lübeck: its proximity to the sea. The seaside resort of Travemünde is a district of Lübeck. As its name implies, it lies at the mouth of the Trave, where the river flows into the Baltic. After sightseeing in the Old Town, just come here, get yourself a Strandkorb — a roofed wicker beach chair - and enjoy the sea breeze. Lübeck is considered northern Germany’s Christmas town. Several Christmas markets invite you to buy presents and drink mulled wine in the Old Town. The biggest is the historical Christmas market in front of the town hall. The building, which dates from 1308, frames the decorated marketplace. Background: Pathogenic variants in the Leucine-rich repeat kinase 2 (LRRK2) gene are the most common known monogenic cause of Parkinson's disease (PD). LRRK2-linked PD is clinically indistinguishable from idiopathic PD and inherited in an autosomal dominant fashion with reduced penetrance and variable expressivity that differ across ethnicities and geographic regions. Objective: To systematically assess clinical signs and symptoms including non-motor features, comorbidities, medication and environmental factors in PD patients, unaffected LRRK2 pathogenic variant carriers, and controls. A further focus is to enable the investigation of modifiers of penetrance and expressivity of LRRK2 pathogenic variants using genetic and environmental data. Conclusions: LIPAD is a large-scale international scientific effort focusing on deep phenotyping of LRRK2-linked PD and healthy pathogenic variant carriers, including the comparison with additional relatively frequent genetic forms of PD, with a future perspective to identify genetic and environmental modifiers of penetrance and expressivity Clinical Trial Registration:ClinicalTrials.gov, NCT04214509. Volume 12 - 2021 | https://doi.org/10.3389/fneur.2021.710572 Background: Pathogenic variants in the Leucine-rich repeat kinase 2 (LRRK2) gene are the most common known monogenic cause of Parkinson's disease (PD) LRRK2-linked PD is clinically indistinguishable from idiopathic PD and inherited in an autosomal dominant fashion with reduced penetrance and variable expressivity that differ across ethnicities and geographic regions Objective: To systematically assess clinical signs and symptoms including non-motor features medication and environmental factors in PD patients unaffected LRRK2 pathogenic variant carriers A further focus is to enable the investigation of modifiers of penetrance and expressivity of LRRK2 pathogenic variants using genetic and environmental data Methods: Eligible participants are invited for a personal or online examination which comprises completion of a detailed eCRF and collection of blood samples (to obtain DNA We plan to enroll 1,000 participants internationally: 300 with LRRK2-linked PD 200 with LRRK2 pathogenic variants but without PD 100 PD patients with pathogenic variants in the GBA or PRKN genes and 200 healthy persons without pathogenic variants Results: The eCRF consists of an investigator-rated (1 h) and a self-rated (1.5 h) part The first part includes the Movement Disorder Society Unified Parkinson's Disease Rating The self-rating part consists of a PD risk factor and the Epworth Sleepiness as well as the Hospital Anxiety and Depression Scales The first 15 centers have been initiated and the first 150 participants enrolled (as of March 25th Conclusions: LIPAD is a large-scale international scientific effort focusing on deep phenotyping of LRRK2-linked PD and healthy pathogenic variant carriers including the comparison with additional relatively frequent genetic forms of PD with a future perspective to identify genetic and environmental modifiers of penetrance and expressivity Clinical Trial Registration: ClinicalTrials.gov data on many populations are still missing no genetic testing guidelines and no clinical trial-ready cohorts exist to date The ROPAD study is still ongoing and continues to identify LRRK2 pathogenic variant carriers internationally It gathers only basic clinical data: age at examination does not allow a systematic in-depth characterization of LRRK2 pathogenic variant carriers Recently published data from the currently largest multinational prospective study that includes LRRK2 pathogenic variant carriers, i.e., the Parkinson's Progression Markers Initiative (PPMI), provide more phenotypic details on LRRK2 pathogenic variant carriers across international sites (6) as the focus of the PPMI study is predominantly on biomarkers it does not cover environmental factors in-depth and only includes participants with a PD diagnosis 2 years or less before enrolment who are untreated with PD medication There remains a gap in combining phenotypic and environmental data on LRRK2 pathogenic variant carriers internationally regardless of the onset of signs and symptoms and their medication status The objectives of the LIPAD study are (1) to provide a systematic characterization of PD patients and unaffected carriers with pathogenic variants in the LRRK2 gene; and (2) to enable the investigation of modifiers of penetrance of LRRK2 pathogenic variants using genetic and environmental data we describe a protocol and a feasibility study of the first 150 participants and give a brief overview of nested studies within LIPAD the LIPAD protocol has also been adapted to take place online due to COVID19 contact restriction measures we expect to have a sufficient number of participants in the LRRK2+/ PD+ family members of pathogenic LRRK2 variant carriers will be asked to participate in the LIPAD study and will be genetically tested for the familial pathogenic LRRK2 variant they will be assigned either to LRRK2+/PD- or HC group Healthy persons without pathogenic variants will be recruited from spouses of study participants or the general population Within an anticipated 24-month recruitment period per site ~25 centers in 10 countries on three continents will be established Each center will have 24 months for recruitment after initiation The majority of the centers will be those already participating in ROPAD additional centers that do not participate in ROPAD but follow LRRK2 pathogenic variant carriers will be invited to become LIPAD sites LRRK2+/PD+: PD patients carrying a pathogenic LRRK2 variant LRRK2+/PD-: unaffected carriers of pathogenic LRRK2 variants genPD: PD patients with pathogenic variants in PD genes other than LRRK2 iPD; LRRK2-/PD+: patients with idiopathic PD from the same populations HC: healthy persons without pathogenic variants Recruited participants have to meet one of the following criteria: (i) clinical diagnosis of PD according to the Movement disorder Society (MDS) diagnostic criteria (ii) first- or second-degree relative of a participant that is positive for a pathogenetic LRRK2 variant (iii) healthy participants with or without a family history of PD in a control group All participants have to be above 18 years of age and have to sign an informed consent form Participants with the following LRRK2 variants will be included in the LRRK2+ group: p.Gly2019Ser (c.6055G>A) Upon completion of genetic screening (e.g. participants are invited for a personal examination using the three-level biomaterial protocol an electronic Case Report Form (eCRF) is administered and blood samples for DNA and household dust for toxicological analyses are collected The three-level protocol was designed to accommodate available laboratory facilities at the different sites. The details of the three levels for biomaterial sampling are listed in Supporting Information Methods S2 in Supplementary Material In case genetic testing has not been performed before a dried blood spot card will be sent for DNA extraction and genetic screening There are no serious safety concerns associated with the study Participants may experience temporary discomfort during venous blood sampling and while answering the questions they are instructed that they are free to omit questions they would rather not answer There are no health risks associated with the collection of urine and house dust Data analysis will be performed at the Institute of Neurogenetics (University of Luebeck which is the systematic characterization of PD patients and unaffected carriers with pathogenic variants in the LRRK2 gene we will describe the frequency of all clinical signs and symptoms including non-motor signs and the most important influencing factors such as sex This will result in raw and corrected frequencies with 95% confidence intervals We will use t-tests for numerical and continuous variables and chi-square tests for categorical variables at a significance level of 0.05 for the comparisons of the clinical signs and symptoms across the groups which is to investigate the modifiers of penetrance of pathogenic LRRK2 variants using genetic and environmental data we will examine penetrance in logistic regression models to quantify the influence of different factors impacting penetrance All LIPAD centers can suggest nested projects which will be coordinated by a Scientific Advisory Board These projects can apply for external funding The following nested studies are planned or have started at the Institute of Neurogenetics (University of Luebeck): Penetrance of LRRK2-linked PD depends on the age of a given individual subject already demonstrate neurodegenerative changes including hyposmia abnormal midbrain hyperechogenicity upon transcranial sonography structural changes of the gray and white matter and functional reorganization of neural networks Although first morphological and functional brain changes in pathogenic LRRK2 variant carriers have already been identified the overall picture is still elusive due to the relatively low number of included subjects in most studies is a promising secondary endpoint for clinical trials given its wide availability To reveal an MRI-based biomarker for LRRK2+/PD+ and prodromal LRRK2+/PD+ we aim to acquire the following MRI modalities: and R2*) to reveal physical tissue properties Diffusion-weighted imaging for multicompartment diffusion models to reveal neuroinflammation and microstructural alterations Neuromelanin imaging to reveal substantia nigra and locus coeruleus degeneration Blood-oxygen-level-dependent functional MRI to identify changes in functional connectivity Magnetic resonance spectroscopy to depict the mechanisms of neurodegeneration such as involvement of energy metabolism due to mitochondrial dysfunction which may be subject to faster change than other aspects of MR-based imaging (e.g. To investigate whether metabolic changes in LRRK2 carriers already exist before the motor manifestation or are secondary to it Energy consumption at rest using indirect calorimetry where energy consumption is determined by measuring the air the subject breathes the proportion of body fat mass and lean mass employing air displacement plethysmography Measurement of physical activity and sleep behavior under everyday conditions using accelerometry The study participants are asked to wear the accelerometer in the form of a wristwatch continuously for 7 days We will perform a genome-wide association study analysis in manifesting vs non-manifesting carriers aimed at discovering genetic modifiers of penetrance of LRRK2 pathogenic variants A comprehensive eCRF has been developed, consisting of an investigator-rated (1 h) and a self-rated (1.5-h) part. The questionnaires are listed in Table 1 We used validated versions of questionnaires and scales in the local languages Content of the LIPAD electronic case report form The first 10 centers across Germany and five international sites have been initiated with further centers currently undergoing ethical review (Figure 2). The first 150 participants have been enrolled (as of March 25th, 2021); Table 2 International centers participating in LIPAD In blue: centers with ethics approval; in black: centers in the process of receiving ethics approval Exemplary demographic and clinical characteristics of the first 150 enrolled LIPAD participants LIPAD is a large-scale international scientific effort focusing on deep phenotyping of LRRK2-linked PD and healthy pathogenic variant carriers including a comparison with additional relatively frequent genetic forms of PD and with a future perspective to identify genetic and environmental modifiers of penetrance and expressivity revealing an important knowledge gap in multinational A comprehensive investigation of modifiers of penetrance and expressivity requires assessment of a considerable number of pathogenic variant carriers Due to the direct enrolment of family members at an international scale the LIPAD study will enable the analysis of modifiers of penetrance in different populations in one setting mainly through the international multicenter ROPAD study will ensure participation of a large number of LRRK2+/PD+ patients which will be conducted on a subset of participants we are aiming to provide a more in-depth phenotypic characterization especially of non-affected carriers of LRRK2 pathogenic variants a complication affecting many patient studies across the world are measures imposed on personal visits to contain SARS-CoV-2 in many countries limiting the possibility for the collection of data and biomaterials To allow the study to proceed under these circumstances we adjusted the protocol and procedures to collect the necessary data online patients receive a package with patient information Then an online appointment with the study team takes place the data is collected and the examination is performed Study participants send signed informed consent forms and a household dust sample back to the study center by post Biomaterials will be taken at a general practitioner's office or the study center at a later time point when study visits become possible again The study will revert to the on-site recruitment as soon as possible after the pandemic restrictions are lifted LIPAD aims for a longitudinal follow-up of its study participants over a 10–15-year time period The exact protocol is currently being developed and potential funding opportunities are being explored The studies involving human participants were reviewed and approved by Ethics Committee (EC) of the University of Lübeck (19-065); EC LÄK Hessen (2019-1364-zvBO); EC LÄK Hamburg (MC-002/20); EC LÄK Brandenburg [AS 35(bB)/2020]; EC Würzburg (161/19_z-sc); EC Kiel (B 292/19); EC Marburg (111/20); EC UK IRAS (project ID: 275553 REC reference: 20/NE/011); EC USA IRB tracking number: 20193494; Pavia The patients/participants provided their written informed consent to participate in this study Neurologisches Fachkrankenhaus für Bewegungsstörungen/Parkinson Özgür Öztop Çakmak University Hospital Marqués de Valdecilla Parkinson's Disease and Movement Disorder Center of Boca Raton Charité University Medicine Berlin University of Pavia and IRCCS Mondino Foundation Department of Brain and Behavioral Sciences University Medical Center Hamburg-Eppendorf TU: organization and execution of the research project design and execution of statistical analysis and writing the first draft of the manuscript E-JV and AR: conception and organization of the research project review and critique of statistical analysis NS and SS: organization and execution of the research project and GG: organization of the research project and JV: review and critique of statistical analysis and review and critique of the manuscript KL: organization of the research project and review and critique of the manuscript and CK: conception and organization of the research project design and review and critique of statistical analysis All authors contributed to the article and approved the submitted version The LIPAD study has been supported by institutional funds (Institute of Neurogenetics AB (NDAL) was funded by Suna and Inan Kirac Foundation ESc was supported by the Luxembourg National Research Fund (FNR) for project A18/BM/12341006 and AR were employed by company CENTOGENE GmbH The authors declare that this study received funding from Centogene GmbH The funder was involved in the study design organization of the research project and review and critique of the manuscript AB is grateful to Suna and Inan Kirac Foundation for their sustained support and both to the Foundation and Koç University-KUTTAM for the excellent research environment created ESc acknowledges the efforts of Begoña Talavera The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fneur.2021.710572/full#supplementary-material Genotype-phenotype relations for the Parkinson's disease genes SNCA LRRK2 in Parkinson disease: challenges of clinical trials and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study LRRK2 parkinsonism in Tunisia and Norway: a comparative analysis of disease penetrance Mitochondrial DNA deletions discriminate affected from unaffected LRRK2 mutation carriers Mitochondrial mechanisms of LRRK2 G2019S penetrance Age at onset of LRRK2 p.Gly2019Ser is related to environmental and lifestyle factors Progression in the LRRK2-asssociated Parkinson disease population The rostock international Parkinson's disease (ROPAD) study : protocol and initial findings The strength in numbers: comprehensive characterization of house dust using complementary mass spectrometric techniques MetFrag relaunched: incorporating strategies beyond in silico fragmentation PubChem in 2021: new data content and improved web interfaces The compTox chemistry dashboard: a community data resource for environmental chemistry Connecting environmental exposure and neurodegeneration using cheminformatics and high resolution mass spectrometry: potential and challenges Clinical and dopamine transporter imaging characteristics of leucine rich repeat kinase 2 (LRRK2) and glucosylceramidase beta (GBA) Parkinson's disease participants in the parkinson's progression markers initiative: a cross-sectional study Age-specific penetrance of LRRK2 G2019S in the Michael J Recurrent LRRK2 (park8) mutations in early-onset Parkinson's disease Klein C and The LIPAD Study Group (2021) LIPAD (LRRK2/Luebeck International Parkinson's Disease) Study Protocol: Deep Phenotyping of an International Genetic Cohort Received: 16 May 2021; Accepted: 13 July 2021; Published: 09 August 2021 *Correspondence: Christine Klein, Y2hyaXN0aW5lLmtsZWluQG5ldXJvLnVuaS1sdWViZWNrLmRl