Monthly Archives: July 2021

Cocktails and Dreams: Behind the Bars of Downtown Casper – K2 Radio

Posted: July 10, 2021 at 3:27 am

Dont tell them to smile more.

The bartenders that work inDowntown Casperare pretty good examples of the range of demographics that make upCasper itself. Its an eclectic group of people, all with their own stories to tell.

Theres Alex, the single mom who has been in customer service for the majority of her adult life and chooses to stay there because she knows shes good at it.

Tessa is a transplant from Las Vegas who, despite her time in Sin City, is still surprised by some of the things she hears on any given night at the bar she works at.

Karen and Jim met and fell in love at the bar they now own and operate together

Gino has been called Caspers Best Bartender, because he takes his job as seriously as a lawyer or a doctor does. He isnt there to be your friend or to wipe your bottom. His job is to serve you drinks and he does it better than almost anybody, at least, according to his peers.

Each and every person that stands behind one of the many bars inCasper has their own story to tell. They have their own life, their own fears, and their own worries. They have their own dreams.

Chances are, youre not a part of them. But, if you mind your manners, follow the Golden Rule and dont stare for too long, youll get some of the best service in the world.

But, whatever you do, dont tell them to smile.

Tamara has been a bartender for three-and-a-half years. She worked at a handful of different establishments before finding herself working for Karen and Jim Kanelos at The Office Bar & Grill. The Office is more of a laid-back kind of place that caters, generally, to an established group of regulars. But The Office is open to anybody looking for a good time and it is Tamaras face that you usually see upon walking in.

Ive learned how to make tons of new drinks since I started working here, Tamara said. Ive learned how to properly pour beers and Ive heard a lot of stories. Its been a lot of fun.

Thats the vibe that both Karen and Jim try to create, for their patrons as well as their employees.

I definitely love my bosses, she stated. Everybody is a team player here, so thats great. Ive gotten to know quite a few people. We have a lot of regulars that come in and I absolutely love them. Everybody is really easygoing.

Naturally, because Tamara is an attractive young woman, she has been the recipient of a multitude of failed pick-up lines.

I had somebody tell me my name was exquisite yesterday, she laughed. But then he said my last name needed to be hottie.

Usually, the bartenders working inany bar will just laugh off these lines. Theyre more concerned with doing their best than about hurting your feelings. Make no mistake, though. Most of the people working behind the bars ofCasper actually do care about the majority of their customers.

Cindy, a bartender at Frostys Bar & Grill has been a bartender for 16 years. She said she has never felt more at home than when she started working at Frostys.

The people that I work with; its been the same group of people, pretty consistently, for the past 3 years Ive been here, Cindy said. We dont have a lot of turnover. Everybody really trusts each other. Everybody works well together. Customers are always good. Its a really homely, comfortable atmosphere to work in.

Comfort is important, especially in customer service jobs. Theres no telling what could happen on any given night.Downtown Casperhas had its share ofinteresting scenarios. Whether it was a girl impaling herself on a wrought-iron fence, two brothers fighting over the same girl or copious amounts of throw-up to be cleaned up, camaraderie is what keeps these workers sane.

Thats especially true in the case of The Gaslight Social. It could be argued that The Gaslight is the most popular bar in town, and its easy to see why. It definitely caters to a younger crowd and the owners of the bar are always trying to innovate. The Gaslight features arcade video games, corn hole tournaments, concerts, volleyball games, beer pong and more. Its more than just a place to sit and have a drink. The owners and employees of The Gaslight want to give their patrons an evening to remember, every time they walk into the bar.

It started off completely, absolutely nuts, remembered Tessa, one of The Gaslights bartenders. We opened right before the Eclipse and it was crazy. I dont even think we slept more than 3-4 hours a night because wed go to work [and stay] until 4 or 5 oclock cleaning the bar, and then wed have to be back here by 2pm.

"But we made so much money.

And really, thats why these people do what they do. They may act like a therapist or a parental figure or a friend, but theyre there to make money.

Sam, another bartender from The Gaslight, said she makes more as a bartender than she did in her previous career.

I was working about 50 hours a week [at my former job] and bringing home the same amount as I would here [at The Gaslight] 3 days a week.

It is that desire to get paid, that has, at least partly, contributed to the community-like atmosphere between the employees.

We rely on each other to make money, Tessa stated. Behind the bar, if somebody isnt doing well or somebody is sick and they need to go home, we all just cover each other. Its our family, and its how we make our money.

Bethanie, another Gaslight Gal, reiterated that point.

"The owners arereally supportive of their staff, Bethanie remarked. Its definitely more or less like a family environment. Theres a lot of understanding if someone is sick or cant make it- we really work together to get that shift covered.

Usually, in the bar or restaurant business, its tough to rely on anybody. Its such an ever-changing industry with extremely high turnover rates, but almost every bar inDowntown Casperhas been compared to a family. This is partly the owners doing, but its also because of the employees and, yes, the customers.

Shaye has been working at the Yellowstone Garage for 3 years. She, too, has compared her job to a family.

We arent really like a work crew here, she stated. Were more like family. John [Huff, owner] treats everybody just like were his. We all get along very well and we all communicate with each other very well.

Shaye continued, saying that when it comes to the outside world, we all hang out and call each other and deal with our problems together.

Bethanie reiterated that point as well.

Youre in it together, she said.

And thats just how it is in The Old Yellowstone District. Whether its Frostys, The Office, Yellowstone Garage, The Gaslight Social or any other place in Downtown Casper, there is a sense of community. Everybody wants to see everybody else succeed, because that means Downtown Casper is succeeding.

Being dead center in the middle of downtown and having all this competitionI dont even want to say its competition at this point, Shaye stated. Were becoming a huge group of people who can provide for everybody and make everyone enjoy downtown a lot more than theyve been able to.

Most of the bars and restaurants inthe Downtown Casper areawill work together. They will call each other to let them know about certain patrons, or situations that might affect the other.

Beyond that, every summer features a multitude of block parties and art walks. Business owners withinthe city have cultivated a sense of community between each other, and its the patrons of these places that have benefitted the most.

Our block parties are some of the best parts about summer, Sam said. All the bars come together and create a fun time. We even have an open container license during the summer. People can just walk around and I think [the block parties] have brought a whole lot of business to the community.

Alex, a bartender at a burger joint-cum-bar called The Branding Iron, said that she believes all of the businesses inthe area are more successful because they work together.

Nobody wants to see anybody else fail, she said. We all support each other and help each other. We all know each other, pretty much. Nobody knows how hard this job is, except for somebody else who is doing the same job.

That, perhaps, is why theres such a camaraderie between all of the businesses downtown. They all relate to each other. They see the same things, deal with the same issues and deflect the same creeps. They all watch out for their customers as well.

We see a lot of Tinder meets and sometimes they dont work out so great, Sam laughed. I feel like we look out for the girls to make sure theyre okay.

The bartenders downtown try to take care of their customers and of each other. Because you never know who might be sitting at the other side of the bar.

Every single night, you hear something youre not expecting to hear, Tessa remarked. I eavesdrop a hundred percent when Im bartending. Most of the time, [people] are talking to you- as a bartender and a therapist and a friend. You hear some of the worst things that you never want to hear, and they just trust you with that as a bartender.

That trust goes a long way, and its something that, ideally, would be reciprocated by the customers. Bartenders would love to trust that their patrons are actually decent people. Sometimes, however, this just isnt the case.

There was this one guy that did the whole Youre beautiful, thing, Shaye remembered. He said I know youre on your feet all day, but you always have a place to sit when you need to.

Shaye, along with most bartenders, can usually laugh off these comments. In a perfect world, however, they wouldnt need to laugh these comments off because the comments wouldnt be made in the first place.

Bethanie said that sometimes it feels like were babysitting grown adults. Sometimes you have to, more or less, get down on their level, like a child, and explain to them the rights and wrongs of communicating with people.

Its not just harassment of the sexual variety that these people need to deal with, either. Nothing ruins a day or kills a mood more than when Karen comes in with her shoes and her haircut and demands to speak to the manager about something that happened 3 weeks ago.

Were humans, Bethanie stated. Were trying to perform the best that we can. It might look like, on the opposite side of the bar, that we might not be doing much to bring you that beer right away, but in our minds, we might have 3 orders already in our head that we need to execute first.

Theyre doing their best. This is made all the more difficult when theyre trying to appease customers, all the while dealing with Brent or Trent or Kent or some other guy with anent name that thinks hes the funniest, most charming guy in the world. We hate to break it you, gents- youre not charming, strippers dont actually like you and the girl serving you a drink is not your mother or your girlfriend.

One thing that does bother me the most is when Im working and men always tell me that I need to smile more, Bethanie said. They say Id be much prettier if I smile or ask me whats wrong. Listen, Im not walking around like Im Cinderella. Its a 12-hour shift. If I smiled for 12 hours straight, I would look like a serial killer.

Despite a few bad apples, however, the community within downtown Casper has been a mostly positive one. Everybody on this side of town wants to see it succeed, from business owners, to employees, all the way down to the customers. Everybody is trying to makethis area something special, something unique and something beautiful.

Without the community, we wouldnt be the bar that we are," Tessa said. "Without the community, period,our owners wouldnt have even had the idea to create the bar that they did, with the outside events and all the concerts.

Without the community, the bars inDowntown Casperwouldnt exist. But it feels like were on the verge of something big here. Everybody wants to be a part of it and everybody wants to see it succeed. So,

Mostly, dont tell your bartenders to smile. Give them a reason to.

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How to get a foot on the City law ladder – Legal Cheek

Posted: at 3:27 am

Ahead of next weeks Legal Cheek-ULaw Summer Virtual Vacation Scheme, Legal Cheeks Will Holmes caught up with ULaws Caroline Carter, Moorgate campus dean and former City lawyer, for her take on the skills future lawyers need

In this conversation we cover four key skills listening, opportunism, networking and resilience that aspiring lawyers should aim to develop and that Caroline Carter, dean of The University of Laws (ULaw) Moorgate campus, knows from first-hand have helped her to be successful at a variety of top City law firms.

Law is a people business, says former City employment lawyer Caroline Carter. You are dealing with people all of the time that range from clients in difficult situations to incredible, delightful and highly professional colleagues. Having risen to become head of employment and senior equity partner at Ashurst, Carters experience has taught her the importance of developing good listening skills. No matter who it is, be super nice to everyone, she advises students with their eyes on a career as a City lawyer.

Indeed, Carter reflected on how she had built a successful practice around her ability to rub along well with everyone, especially fellow lawyers at other firms who she were representing the opposing side in disputes. She acknowledges that really listening to clients needs and concerns, as well as the ability to take on as much feedback as possible had helped her to develop into a successful lawyer.

And Carter certainly hasnt stopped listening in her new role as dean of ULaws Moorgate campus. She says she has spent her first weeks in the job listening to a host of different people at all levels. Although not coming from a teaching background, Carter has married together her 30 years of experience as a lawyer and her work as a non-executive director for a host of social mobility in education organisations, the post-graduate focused Cranfield University and the all-girls state school Copthall. It is her ability to continually listen and learn from others around her that has helped her to take her career down this exciting new path. Her focus is to try and share these skills with ULaw students to help them to become adaptable and well-rounded lawyers.

Carters top advice to aspiring lawyers is to get stuck in. Online events, networking, lectures, vac schemes, open days theyre all really useful ways to get experience. Her mantra is that no experience is a bad experience, adding, dont close your mind to anything. Get to all of the online sessions, it could be worth it!.

In Carters case, being opportunistic was what got her foot on the City law ladder. Having overheard that a fellow student at law school no longer wanted a training contract at Theodore Goddard (which merged to become Addleshaw Goddard in 2003), Carter applied to the firm. She modestly claims that she got lucky and was offered a training contract at the firm.

In her role at ULaw, however, Carter wants to ensure that aspiring lawyers have as many opportunities as possible. The Universitys Tech Research Academy ULTRA, employment team and educational technology is all aimed at equipping students to take advantage of as many opportunities as possible, she tells me.

Networking is an area that the pandemic has radically changed, with virtual events often dictating the opportunities students have to start building connections. On this point, Carter recommends a clear strategy: Have three things you want to hear about and one thing that you could get involved with. According to her, this targeted approach can help make the most of the exposure they get to members of the legal profession. She also recommends sending thank you emails and follow-ups or even something in the post!.

This is especially true regarding interviews. Carter, who enjoyed stints at Theodore Goddard and Linklaters before finally settling down at Ashurst, tells me shes always in contact with trainees and people she has interviewed in the past to give some useful advice. The same applies if you have not been successful. Whether you get feedback, a new connection or no response, the golden rule for aspiring lawyers is always ask.

Located a stones throw away from many top City firms, ULaws Moorgate campus should help its students with this. Carter hopes to really reinvigorate these strong City ties, as the campus reopens.

In Carters career, no two days were ever the same. Resilience and crisis management is therefore a real differentiator among junior lawyers. Carter explains that when picking between two closely matched candidates at training contract interview, she would always ask herself if the chips were down at 2am, who would you want to be there?.

So, how can trainees develop these skills? Carter tells me that doing applications is a test of ones self-reflection. She recommends that candidates reflect carefully on transferable skills and find that most will be amazed at how they can build up a picture of their own experiences when they really think about. A variety of odd jobs and different experiences working in a supermarket, as a teacher, a volunteer abroad or at home can really make the difference and shines through when the going gets tough as a junior. As the former City lawyer points out, academics are only a part of the picture.

In interviews, it is also important to be aware of how you are presenting yourself, which comes with practice. With many interviews taking place virtually at the moment, Carter suggests getting in the zone as though you were really doing the interview in a swanky City office, adding that candidates would be well-advised to avoid any suit-jacket-tie-and-underpants interviews!

Ultimately, Carters objective at ULaw is to make people feel confident about embarking on their legal careers. With a unique passion for education and bags of legal experience, her students certainly look like theyre in good hands.

Caroline Carter will be speaking at The Legal Cheek Summer 2021 Virtual Vacation Scheme, run in partnership with The University of Law, which takes place from Monday 12 July until Friday 16 July. You can apply to attend the scheme, which is free, now.

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Italys Resurgence Leaves Them on the Cusp of European Glory – The Ringer

Posted: at 3:27 am

The road toward triumph in a major soccer tournament must at some point take the form of an epic quest, and so the manner of Italys win over Spain was duly mythical. They defeated their Mediterranean rivals in a penalty shootout, prevailing by four successful kicks to two, and in doing so they showed an astonishing level of resilience. Against Belgium in the previous round, a match many of us thought featured the two best teams at Euro 2020, Italy were supreme for long periods; against Spain, they were thoroughly human. It is hard to imagine a midfield of Marco Verratti, Nicol Barella, and Jorginho being consistently on the back foot against anyone, but this is what they experienced against Spain, assailed by the often majestic trio of Koke, the swiftly aging but still sublime Sergio Busquets, and, of course, the prodigy that is Pedri.

Pedri, Pedri. It is difficult to remember such a young and diminutive figure being so dominant in a fixture of this importance. Following this game, Spain coach Luis Enrique said that he had never seen anyone do what Pedri did, not even Andrs Iniesta. Pedri is a man of deceptive strength: He may be as slim as a candle, but you couldnt extinguish his flame with a whirlwind. At the end of 90 minutes, the teams tied with one goal apiece, Sid Lowepresumably as awestruck as the rest of ustweeted that Pedri has completed, erm, ALL of his passes.

Yet Italy still found a way to prevail. They started this game with the same intensity with which they had shoved Belgium aside, before realizing that Spain were somewhat more resistant to their storm. It was poignant to see Italy create some of their best openings down the left, because, as well as Emerson played, those ventures forward would probably have been all the more efficient had they been led by Leonardo Spinazzola, the wingback who had been in exceptional form before an injury against Belgium ruled him out of the tournament.

After Spain endured Italys early onslaught, they then hatched a possibly lethal scheme of their own, and at the center of it was Busquets. Watching Busquets, even in his later years, is reminiscent of the opening lines of H.G. Wellss The War of the Worlds. Wells, describing the Martians as they plotted their invasion of Earth, observed that:

Across the gulf of space, minds that are to our minds as ours are to those of the beasts that perish, intellects vast and cool and unsympathetic, regarded this earth with envious eyes, and slowly and surely drew their plans against us.

Busquets, every bit as brilliant, calculating, and unsympathetic as a Martian covetously eyeing our Earth, began to prompt attack after attack. The most effective opponent of his scheming was Barella, whose excellent movement showed that he understood the golden rule of every midfield battle: you cannot, under any circumstances, allow Busquets to walk. If you let this man stroll about the center circle, he will destroy you. As regal as Busquets so often was in this game, Barella made sure to unsettle him whenever he could. After all, if you are a young upstart in the presence of an elderly king, it is your duty to keep knocking the crown from his head.

While Italy went for width as the main emphasis of their attack, Spain went for narrowness, concentrating their forces through the middle. Thats where Dani Olmo and Mikel Oyarzabal, starting in place of the much-maligned lvaro Morata, sought to make their claims as national heroes. But glory evaded them. Both players missed significant opportunities in the first half, and in doing so they reminded us just how hard it is to score at this levelbecause you arent just aiming at the net, you are aiming at history. Their failures in that opening period foreshadowed the pain to come.

It was fitting that, in a match steeped in footballing pedigree, the person to open the scoring should come from some of the games finest lineage. The first goal came after an hour, a magnificent strike from Federico Chiesa, the Juventus forward whose father Enrico had played 22 times for Italy. Chiesa had already found the net in the knockout stages against Austria, breaking the deadlock in extra time. Here he did so after an exhilarating counterattack, Italy surging forward with the urgency of locusts before he steered the stray ball into the far corner of Unai Simns goal. At that point, Spain appeared to be doomed. Italys defense, led by the legendary Giorgio Chiellini, looked as distinguished and immovable as the walls of a medieval city; meanwhile, Spain seemed short of the energy and creativity for a successful siege. At which point, enter Morata.

Oh, Morata. Euro 2020 has been, shall we say, an extraordinary emotional journey for him. It may be some time before he processes it in full: He has given us a spectacular and decisive goal (against Croatia), a series of spectacular misses (against Slovakia, Sweden, and, yes, against Croatia), some superb forward play, but never a sense of reliability. During that run of games, his family was shamefully approached and intimidated by supporters of the national team who were furious at his poor form: eternal proof that even during a deadly pandemic there are still people on this earth who absolutely can be trusted not to retain a sense of perspective. Here, having been dropped to the bench to make room for Oyarzabal as an extra midfielder, Morata was introduced to be Spains savior. It was a role for which he seemed utterly ill-fitted; and yet, with 10 minutes to go, he played it to perfection. Rushing onto a beautifully precise pass from Olmo, he did what no player apart from Romelu Lukaku at Euro 2020 had done to Gianluigi Donnarumma: he calmly sent him the wrong way. Spain 1, Italy 1. Morata was redeemed, his nation was euphoric, and the game advanced to extra timeand then, perhaps inevitably, to penalties.

Never has a form of conflict resolution been both so brutal and yet so utterly just as the penalty shootout. Never have the football gods been so keen to identify someone to have a crucial penalty saved as Morata was here. The strikers joy lasted all of 40 minutes, his effort swatted aside by Donnarumma as Italy swaggered into the final. While Moratas journey ended in tragedy, Italys soared toward legend, their makeover underneath Roberto Mancini complete. They have conceded only two goals from open play all tournament. When Mancini took charge just over three years ago, in May 2018, they had failed to qualify for the World Cup a few months before, a humiliation they had not experienced in 60 years. Now they are back at the games high table, and they have now been so thoroughly battle-tested that they are well-placed to enjoy the banquet. We have seen them in all their guises so far at Euro 2020: showmen in the group stages, elite swordsmen against Belgium, and indomitable survivors against Spain. They can rightly feel confident theyll be conquerors on Sunday.

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Freedom of the Road: What are the Rules of Driving? – Legal Reader

Posted: at 3:27 am

You can only have the freedom of the road by following the rules of good driving. Always buckle up before hitting the road. Make sure to keep your license on you before leaving. Never drive if you think you are high drunk. Know the speed limit and drive safely.

Getting a drivers license doesnt mean you are now free to ride your car like a rollercoaster on the road. Driving means having control over the vehicle and having a sense of responsibility. To some teens, driving may mean freedom as they can go anywhere they want whenever they want.

And so, it is essential to know the rules of driving to avoid accidents and ensure safe driving.

Do you know wearing a seatbelt can lessen the risk of terrible injuries in an accident by 40% to 50%? Wearing a seatbelt is the first very essential thing to do for a driver. It prevents you from being thrown towards the windshield and protects you from other wounds during any misfortune.

Always wait for the light to turn green. Not following the traffic signals can result in accidents that may cause damage to the vehicle but as well as to the driver. Remember, the red signal crossing is prohibited. Traffic signals also include mandatory road signs to be followed.

From teens to grownups, it is compulsory to keep a check on your vehicle. This will ensure the cars safety and prevent it from sudden breakdowns. Always check on the fluids, test the lights, battery, and engine oil. You can also hire the best car expert group to get your vehicle insured just in case of any mishap. The group will also guide you about the proper care of the car and will also help you economize on maintenance and repairs.

While driving, make sure you dont follow the car in front of you too closely. Distance prevents collision between vehicles and ensures the passengers safety. Maintaining a safe space will help the driver to react on time if the car ahead makes an unexpected stop or turn. You should at least allow a vehicle to vehicle distance of about 50m at 50km/h and 80m at 80km/h.

Plain view: Man opening bottle behind the wheel; image by energe.com, via Pexels.com.

Drinking then driving isnt worth the risk. It is prohibited and one of the golden rules of driving. Make sure youre not behind the wheel once you are drunk, as alcohol can cause numerous impairments that may lead to a car crash. A high intake of alcohol causes blurred vision and loss of consciousness. Do not drive after taking medicines that include alcohol, which may also lead to the same consequences.

Drunken driving is a criminal offense and it may cost you a significant fine and may also get you behind bars.

Speeding can lead to death or permanent lifetime disabilities. Youngsters now like speeding while enjoying themselves with friends and not knowing the fatal consequences they might face. Make sure to follow the standard speed limit so, in case of any crash, the driver gets time to react accordingly.

Driving requires double the focus than any other tasks. Approximately more than 60% of accidents happen due to getting distracted and taking eyes off the road. Cell phones, loud music, taking hands off the wheel, applying makeup, eating while driving are some of the distractions that cause severe damage to the passengers.

To reduce the risk of a crash, pull over to answer your call or ask for directions.

A very crucial rule of driving is that you stay in your lane and follow discipline. Shifting more than one lane at a time is not permitted and is considered a lane violation.

Make sure you share the road by making way for emergency vehicles such as police, ambulances, and fire engines. You can do it by moving your vehicle slightly to the side while driving. Dont forget to give a signal before changing lanes.

Be very careful when approaching pedestrian crossings. It is possible that some people might not see you coming and how hard you may hurt them. Be extra watchful near schools, parks, and residential areas where children are more likely to be found crossing the road. Do not drive until all the people are off the crossing.

Driving in bad weather requires eyes on the road, especially when its foggy, rainy, and snowy out there. Allow a distance of about 5-6 seconds between cars, maintain the speed limit, and be careful on slippery roads, so you dont end up in a rear-end collision. Dont forget to make sure that the lights (fog lamps) are functioning during fog so it will help other drivers to see you coming.

It is vital to learn how to overtake if necessary without endangering yourself or others while driving. Overtaking is more likely to be banned on narrow roads. If doing so, you will be found guilty and left with a fine. Try avoiding overtaking vehicles at night time as it is more dangerous. Also, make sure that the road ahead is visible while you overtake.

Large and heavy vehicles contribute to a higher risk of accidents. Make sure to watch and look out for bulky turning vehicles and, if not, there are chances of your car getting hit by it. Do not follow trucks too closely as that can result in crashes.

Remember the rules of driving on a one-way road. You are not allowed to drive in the opposite direction except for the one thats permitted.

Expressways and highways are one-way traffic. Accidents caused on these roads can be dreadful if the rules told are ignored.

Conclusion

You can only have the freedom of the road by following the rules of good driving. Always buckle up before hitting the road. Make sure to keep your license on you before leaving. Never drive if you think you are high drunk. Know the speed limit and drive safely.

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Mapping the cellular origin and early evolution of leukemia in Down syndrome – Science

Posted: at 3:26 am

Down with leukemia

Down syndrome is a congenital disorder caused by the trisomy of chromosome 21, and it is associated with a greatly increased risk of leukemia with origins in fetal development. Infants with Down syndrome are often born with a preleukemic condition, which later resolves in most cases. By using gene-edited human cells implanted into mouse models, Wagenblast et al. recapitulated the development of preleukemia and leukemia in the context of Down syndrome (see the Perspective by Roberts and Vyas). A specific mutation triggered a preleukemic condition in the context of trisomy 21 as expected, but progression to full-blown leukemia required a different genetic path and was not dependent on trisomy 21.

Science, abf6202, this issue p. eabf6202; see also abj3957, p. 155

Leukemia is the most common cancer in children, with the first genetic alterations often occurring during fetal development. These initiating events generate preleukemic cells, which are the evolutionary ancestors of leukemia that arises after birth. Because of our inability to directly access human fetal preleukemia, the identity of the cell of origin and the steps of leukemia evolution remain largely unknown. Down syndrome leukemogenesis represents a disease setting to study human preleukemia and the evolutionary steps that lead to fully transformed leukemia. Up to 30% of children with Down syndrome (trisomy 21) exhibit a preleukemic transient abnormal myelopoiesis (TAM) and, overall, have a 150-fold increased risk of developing myeloid leukemia within the first 5 years of life. However, the mechanism by which an extra copy of chromosome 21 predisposes to preleukemia and leukemia remains unclear.

Understanding Down syndrome leukemogenesis requires a humanized model that faithfully recapitulates the full developmental spectrum of premalignant and malignant stages of Down syndrome leukemia. Using CRISPR/Cas9mediated gene editing in human disomic and trisomic fetal liverderived hematopoietic stem and progenitor cells and xenotransplantation, we developed a model with which to characterize the genetic events and cellular contexts underlying the preleukemic and leukemic phases of Down syndrome leukemogenesis.

Trisomy 21 hematopoietic stem and progenitor cells (HSPCs) showed reduced proliferation in vitro and generated smaller grafts in xenotransplanted mice, with reduced serial transplant ability, as compared with that of disomic HSPCs. Preleukemia was initiated in trisomy 21, but not disomic, long-term hematopoietic stem cells (LT-HSCs) when mutations in the erythroid-megakaryocyte transcription factor GATA binding protein 1 (GATA1) were introduced, which led to exclusive expression of the short isoform (GATA1s). Subsequent leukemic progression could occur in multiple stem and progenitor populations, was independent of trisomy 21, and induced through deletion of cohesin genes, including STAG2 (STAG2ko). Serial engraftment in mice showed that GATA1s-induced preleukemia underwent spontaneous resolution, which contrasted with the persistent ability of the GATA1s/STAG2koinduced leukemia to engraft serially in mice. Leukemic progression was developmentally restricted to fetal and early postnatal stages; adult-derived bone marrow HSPCs were unable to undergo GATA1s/STAG2ko-induced leukemic transformation. We identified a molecular mechanism by which three chromosome 21 microRNAs (miRNAs) contributed to the predisposition toward preleukemia initiation. Simultaneous overexpression of miR-99a, miR-125b-2, and miR-155 in normal disomic LT-HSCs recapitulated a trisomy 21like hematopoietic state, as assessed through comparable lineage differentiation, reduced self-renewal capacity, and similar gene expression and open chromatin accessibility profile. Removal of these miRNAs in trisomy 21 LT-HSCs inhibited GATA1s-induced preleukemia development. Using secondary xenotransplantations of defined cell populations, we identified CD117+/KIT proto-oncogene (KIT) as a marker of disease-driving cells. Pharmacological KIT inhibition targeted preleukemic stem cells, both in GATA1s-induced preleukemia and in primary Down syndrome preleukemia patient samples.

Collectively, our results provide insight into how human preleukemia and leukemia evolve in fetal life and early childhood. We were able to identify distinct cellular origins and effects of trisomy 21 for preleukemia initiation and leukemia progression. Predisposition to preleukemia in Down syndrome is affected by overexpression of distinct chromosome 21 miRNAs, specifically in the preleukemic LT-HSC cell of origin. Our study reveals the relevance of the cellular and developmental status of the cell of origin during leukemogenesis, which begins to explain why genetic drivers can be distinct between pediatric and adult acute myeloid leukemia. KIT inhibitors targeted preleukemic stem cells, providing proof of principle for early prevention strategies in childhood leukemia that may be able to inhibit leukemia progression, and these results encourage further preclinical and clinical assessment.

Down syndrome preleukemia originated in long-term hematopoietic stem cells (LT-HSCs) through mutations in GATA1, leading to the expression of the short isoform GATA1s. Progression toward leukemia occurred in various stem and progenitor cells through mutations in cohesin factors such as STAG2. Predisposition to preleukemia was affected by chromosome 21 miRNAs, and pharmacological inhibition of KIT targeted preleukemic stem cells.

Children with Down syndrome have a 150-fold increased risk of developing myeloid leukemia, but the mechanism of predisposition is unclear. Because Down syndrome leukemogenesis initiates during fetal development, we characterized the cellular and developmental context of preleukemic initiation and leukemic progression using gene editing in human disomic and trisomic fetal hematopoietic cells and xenotransplantation. GATA binding protein 1 (GATA1) mutations caused transient preleukemia when introduced into trisomy 21 long-term hematopoietic stem cells, where a subset of chromosome 21 microRNAs affected predisposition to preleukemia. By contrast, progression to leukemia was independent of trisomy 21 and originated in various stem and progenitor cells through additional mutations in cohesin genes. CD117+/KIT proto-oncogene (KIT) cells mediated the propagation of preleukemia and leukemia, and KIT inhibition targeted preleukemic stem cells.

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Draymond Green discusses the evolution of Damian Lillard playing with a chip on his shoulder – NBC Sports

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Rip City knows the tremendous value of Damian Lillards skillset and leadership qualities.

But now the world is going to learn more about all of Lillards characteristics.

As Lillard and Team USA gear up for this years Summer Olympics, head coach Gregg Popovich is thankful to have such a Lillard on his roster as Lillard joins the squad for the first time.

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Whenever I talked to Dame it was about letting him know that he was valued and we'd love to have him on the time. Period, Popovich said following Thursdays practice.

Coach Pop also discussed the value and importance of having two Teammates of the Year recipients in Lillard and Jrue Holiday.

We have such a short time together and somebodys got to lead. Somebody has to take on the responsibility to understand, to keep everybody focused.

Team USA head coach Gregg Popovich

Those kind of leadership skills are necessary, mandatory, Popovich added. It makes everything a lot more difficult if everybody is just looking around at everybody else and they dont know who to look to. So, guys like Jrue and Damian are very valuable in that sense.

With the videos on social media of Team USA scrimmages in Las Vegas, it seems Lillard and Warriors star Draymond Green are working well together both on and off the court.

Green, who earned a gold medal with Team USA during the 2016 Olympic Games,undoubtedlyrespects Lillards game, but from the sounds of it, he may respect the Trail Blazers point guards mind even more.

We all know that Dame has carried a huge chip on his shoulder, Green began to explain. From being a guy who was not recruited by many high-majors if maybe one or two. Going to Weber State, coming into the draft, a lot of people knowing that this guy is good, but doubting him because he went to a small school, the story goes on and on.

Green also explained the importance of the evolution of Lillard playing with a chip on his shoulder.

I think one of the great things about Dame is he still carries that chip on his should, but the way you carry a chip on your shoulder, you cant carry the same chip on your shoulder that you had as a rookie You have to learn how to wear that chip differently and one of the most powerful things about Dame has is he continues to wear that chip on his shoulder, but knows how to wear it.

Draymond Green

After leading the Blazers to a sixth place finish in the Western Conference last season with a 42-30 overall record, while averaging 28.8 points and 7.5 assists, Lillard says he had a sour taste in his mouth after an early First Round playoff exit.

As eager as Lillard is for Olympic play to tip-off, Green sounds just as excited to play alongside Dame.

Obviously one of the best shooters in our game, one of the most prolific scorers in our game, and also an incredible leader and an incredible point guard, Green said.

Hes from Oakland, and he embodies that, he carries that, he carries that toughness. And that makes all the difference when he takes the floor.

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Eaton: The Evolution of Taylor Swift The Minnesota Daily – Minnesota Daily

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We can learn more from the pop icon than just how to write a killer breakup anthem.

Taylor Swift is an icon. Regardless of your opinion on her music, her impact on popular culture is hard to ignore. Now, shes re-recording her first five studio albums made under the music label Big Machine, with the public reason being to reclaim rights over her previous work after it was sold to music executive Scooter Braun. But, these re-recordings are reflective of her growth, not only as an artist, but as a public and political figure.

Swift largely stayed out of politics early in her career, and white supremacist groups latched onto her silence as support for their cause. It wasnt until 2018 that Swift began to come into her own in the political sphere. Now, in 2021, Swift is a prominent advocate for LGBTQIA+ rights, gun control and the freedom to choose. Shes an outspoken feminist, dropping tracks like The Man and Mad Woman which speak to the trials of misogyny in everyday life.

Re-recording her albums is more than just a f you to Scooter Braun. By Swifts account, Braun has repeatedly bullied her. He also closely associates with Kanye West, who Swift has a contentious relationship with following the 2009 MTV Music and Video Awards. In re-recording her albums, her goal is to override her previous work keeping Braun from profiting off of her music. Its a manifestation of how she has changed and grown as an artist, a reclamation of her identity and reputation. She exerts control over her music, releasing all of the songs she wants, not simply the ones deemed good enough for the album by producers.

In the era of cancel culture, proving personal growth by literally going back over your past is an influential move.

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For a long time, Swift remade herself with each album. She didnt just release songs, she changed her personal style, altered her public image and curated a musical theatre production for each world tour. As she grew from a teenage country singer to the 31 year old pop icon she is now, her sound grew with her.

Her last two albums, Folklore and Evermore, have been a departure from that. They tell the stories of other people, real and make-believe, and have none of the pomp and circumstance of her earlier work. Swift is no longer conforming to the music scene. Shes not a malleable teen girl listening to the whims of producers and agents trying to make her famous; shes come into her own. That sense of self allows her to re-record all of these previous albums in a way that is true to who she truly is.

Swifts actions do more than provide her fans with content to consume. Not only does she regain the rights to her previous songs, shes able to alter her earlier music to accurately reflect who she has become and leave behind who she is not. She is no longer a politically silent poster child for neo-Nazis and white supremacists, nor is she an innocent teenage girl singing country ballads about heartbreak. Taylor Swift is simply Taylor, without the perceptions and misconceptions of society.

I am looking forward to Taylors new tunes and seeing the path she continues to carve for herself, both politically and personally. And, as my roommate said, Im surprised its taken you this long to write about Taylor Swift.

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Evolution of the dad – Ars Technica

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Enlarge / The "bearded hipster dad," as documented by Getty Images, is a particularly unique creature in the larger animal kingdom. (Well, technically, all human dads are.)

Jessie Casson / Getty Images

Lee Gettler is hard to get on the phone, for the very ordinary reason that hes busy caring for his two young children. Among mammals, though, that makes him extraordinary.

Human fathers engage in really costly forms of care, says Gettler, an anthropologist at the University of Notre Dame. In that way, humans stand out from almost all other mammals. Fathers, and parents in general, are Gettlers field of study. He and others have found that the role of dads varies widely between culturesand that some other animal dads may give helpful glimpses of our evolutionary past.

Many mysteries remain, though, about how human fathers evolved their peculiar, highly invested role, including the hormonal changes that accompany fatherhood (see sidebar below). A deeper understanding of where dads came from, and why fatherhood matters for both fathers and children, could benefit families of all kinds.

If you look at other mammalian species, fathers tend to do nothing but provide sperm, says Rebecca Sear, an evolutionary demographer and anthropologist at the London School of Hygiene and Tropical Medicine. Moms carry the burden in most other animals that care for their kids, too. (Fish are an exceptionmost dont tend their young at all, but the caring parents are usually dads. And bird couples are famous for co-parenting.)

Even among the other apes, our closest relatives, most dads dont do much. That means moms are stuck with all the work and need to space out their babies to make sure they can care for them. Wild chimps give birth every four to six years, for example; orangutans wait as long as six to eight years between young.

The ancestors of humans, though, committed to a different strategy. Mothers got help from their community and their kin, including fathers. This freed them up enough to have more babies, closer togetherabout every three years, on average, in todays nonindustrial societies. That strategy is part of the evolutionary success story of humans, Gettler says.Enlarge / Don't let this male gorillas scowl fool youhe likely lets kids hang around.

Paul Zinken/picture alliance via Getty Images

Some clues about the origin of doting fatherhood come from our close primate relatives. Stacy Rosenbaum, a biological anthropologist at the University of Michigan, studies wild mountain gorillas in Rwanda. These gorillas provide intriguing hints about the origins of ape dads, as Gettler and coauthors Rosenbaum and Adam Boyette argue in the 2020 Annual Review of Anthropology.

Mountain gorillas are a type of eastern gorilla. They differ from western gorillasa separate species, more often seen in zoosin their habitat and diet. Rosenbaum is more interested in another thing that sets mountain gorillas apart: Kids spend a ton of time around males, she says.

Those males may or may not be their dads. Male mountain gorillas dont seem to know or care which young are theirs. But nearly all males tolerate the company of kids. Unlike any other great ape thats been studied in the wild, these malesbruisers twice the size of females, with huge muscles and teethare essentially babysitters. Some pick up the kids, play with them and even sleep cuddled together.

This male company can protect very young gorillas against predators, and it keeps the young from being killed by intruding males. Another important benefit might be social, Rosenbaum speculates. The young gorillas mingling around an adult male might pick up social skills like human toddlers do from their peers at daycare. Additionally, research has shown that the relationships between young gorillas and adult males persist as those kids grow up.

Another tantalizing hint about how male gorillas benefit the young in their group comes from a recent paper on young mountain gorillas whose mothers died. Losing their mothers didnt make these orphans more likely to die themselves, the researchers found. Nor did they experience other costs, such as a longer wait before having their own young. The orphans relationships with others in their group, especially dominant males, seemed to protect them from ill effects.

Mountain gorilla males arent the only primates to ally with kids. Adult male macaques also spend time with young. And baboon males form friendships with females and their young, which are often (but not always) their own offspring. These behaviors cost the male primates almost nothing. So while the males may give their own kids a survival boost, its not a big deal if they spend time with some unrelated kids too.

But babysitting may benefit male gorillas in another way, too: by making them more attractive. One of our speculations is that females actually prefer mating with males who do a lot of interacting with kids, Rosenbaum says. Shes found that male gorillas who do more babysitting earlier in life go on to father many more children when theyre older. Macaques, too, seem to be more attractive to females if theyve spent more time hanging out with kids.

Anthropologists used to assume that fatherly behavior could evolve only in monogamous animals, Rosenbaum says. Species like the mountain gorillas undermine that assumption. They also show that, despite what scientists have long thought, male animals dont have to choose between spending their energy on mating or parenting. It seems taking care of kids can be a way of getting mates.

Studies of human dads and stepdads have hinted at the same idea. A lot of guys will willingly enter into relationships with kids they know arent theirs, says Kermyt Anderson, a biological anthropologist at the University of Oklahoma. That investment might seem paradoxical from an evolutionary perspective. But Andersons research suggests that men invest in stepkids and even biological kids partly as an investment in their relationship with the mother. When that relationship ends, fathers tend to become less involved.

A human dad who cares for his children or stepchildren is different, of course, from an ape or monkey who just lets kids hang around. But Gettler and Rosenbaum wonder whether our own ancestors had similar habits to a mountain gorilla or macaque. Under the evolutionary pressures they faced, these friendly tendencies toward kids could have ratcheted up into devoted fatherhood.

Its clear human fathers are unusual in their attention to their children. However, its also clear that fatherhood in humans is quite variable, Sear says. Not all dads are doting, or even present.

But that doesnt necessarily affect basic survival. In a 2008 paper, Sear and coauthor Ruth Mace asked whether children with absent fathers are likelier to die. They reviewed data on child survival from 43 studies of populations around the world, mostly those without access to modern medical care. They found that in a third of the studies looking at fathers, kids were more likely to survive childhood when their dad was around. But in the other two-thirds, fatherless kids did just as well. (By contrast, every study of children without mothers found they were less likely to survive.)

That is not what you would expect to see if fathers are really vital for children to thrive, Sear says. Rather, she suspects that whats vital are the jobs fathers perform. When a father is missing, others in the family or community can fill in. It may be that the fathering role is important, but its substitutable by other social group members, she says.

What is that role? Historically, Gettler says, anthropologists have viewed fatherhood as all about provisioningbringing home the bacon, literally. In some foraging communities, more successful hunters also father more kids. But Gettler hopes to help expand the definition of a dad. Research has shown that fathers can have important roles in directly caring for their children, for example, and teaching children language and social skills. Fathers may also help their children by cultivating relationships in their communities, Gettler says. When it comes to survival, Networking can be everything.

A dads job also varies culturally. For example, in the Republic of the Congo, Gettler works with two neighboring communities. The Bondongo are fishers and farmers; they value fathers who take risks to gain food for their own families. Their neighbors, the BaYaka, are foragers who value fathers who share their resources outside their families.

In the West we have this idealization of the nuclear family, says Sear: a self-reliant, heterosexual couple in which Dad does all the provisioning and Mom all the childcare. But worldwide, she says, families like this are very rare. A childs biological parents may not live together exclusively, for life or at all, Sear writes in a recent paper. Childcare and food can come from either parentor neither. Among the Himba of Namibia, for instance, children are often fostered by extended family.

Possibly the key defining feature of our species is our behavioral flexibility, Sear says. Assuming that certain roles are natural for fathers or mothers can make parents feel isolated and stressed, Sear writes. She hopes research can broaden our understanding of what fathers are for, and what a human family is. That might help societies to better support families of all kindswhether they have dads like Gettler who are busy chasing the children around, or dads who are away fishing, or no dads at all.

I think we need to take a much more nonjudgmental view of the human family, and the kinds of family structures in which children can thrive, Sear says, to improve the health of mothers, fathers and children.

Editor's note: This story was updated on June 16, 2021, to correct the name of the country where the Bondongo and BaYaka live. It is the Republic of the Congo, not the Democratic Republic of the Congo, as was originally stated.

Elizabeth Preston is a freelance science journalist who lives in the Boston area with her husband and two small, highly dependent primates.

This article originally appeared in Knowable Magazine, an independent journalistic endeavor from Annual Reviews. Sign up for the newsletter.

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New fossil sheds light on the evolution of how dinosaurs breathed – UMN News

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Using an exceptionally preserved fossil from South Africa, a particle accelerator, and high-powered x-rays, an international team including a University of Minnesota researcher has discovered that not all dinosaurs breathed in the same way. The findings give scientists more insight into how a major group of dinosaurs, including well-known creatures like the triceratops and stegosaurus, evolved.

The study is published in eLife, a peer-reviewed open access scientific journal for the biomedical and life sciences.

Not all animals use the same techniques and organs to breathe. Humans expand and contract their lungs. Birds have air sacs outside their lungs that pump oxygen in, and their lungs dont actually move. For a long time, paleontologists assumed that all dinosaurs breathed like birds, since they had similar breathing anatomy. This study, however, found that Heterodontosaurus did notit instead had paddle-shaped ribs and small, toothpick-like bones, and expanded both its chest and belly in order to breathe.

Heterodontosaurus is the oldest dinosaur in the Ornithischian line, one of three major dinosaur groups that includes Triceratops, Stegosaurus, and other duck-billed dinosaurs. The other groups are sauropods, or longnecks, and theropods like the T-Rex.

We actually have never known how these [Ornithischians] breathed, said Viktor Radermacher, lead author of the study and a Ph.D. student in the University of Minnesotas Department of Earth and Environmental Sciences. The interesting thing is that Heterodontosaurus is the ancestor of this group and it has these [newly discovered] pieces of anatomy, but its descendants don't. What that means is that Heterodontosaurus is a missing link between the ancestors of dinosaurs and the bigger, charismatic species we know. This gives us a whole bunch of information and fills in some pretty glaring gaps in our knowledge of the biology of these dinosaurs.

The researchers analyzed the new Heterodontosaurus specimen with high-powered x-rays generated from a synchrotrona giant, donut-shaped particle accelerator that spins electrons at the speed of lightat the European Synchrotron Radiation Facility (ESRF) in France. Using those x-rays, they were able to digitally reconstruct the skeleton and identify the dinosaurs unique features.

Heterodontosaurus lived in the early Jurassic period, about 200 million years ago, surviving an extinction at the end of the prior Triassic period. Understanding how this dinosaur breathed could also help paleontologists figure out what biological features allowed certain dinosaurs to survive or caused them to go extinct.

The takeaway message is that there are many ways to breathe, Radermacher said. And the really interesting thing about life on Earth is that we all have different strategies to do the same thing, and we've just identified a new strategy of breathing. This shows that utilizing dinosaurs and paleontology, we can learn more about the diversity of animals on Earth and how they breathe.

In addition to Radermacher, the research team included Vincent Fernandez, an ESRF beamline scientist and X-Ray technician at the Natural History Museum, UK; Emma Schachner, an associate professor at Louisiana State University; Richard Butler, a professor of palaeobiology at the University of Birmingham, UK; Emese Bordy, an associate professor at the University of Cape Town, South Africa; Michael Naylor Hudgins, a grad student at the University of Alberta, Canada; William de Klerk, emeritus curator of the Department of Earth Sciences at Rhodes University in Makhanda, South Africa; Kimberley Chapelle, a postdoctoral fellow at the American Museum of Natural History in New York; and Jonah Choiniere, a professor of comparative palaeobiology at the University of the Witwatersrand, South Africa.

The research was funded by grants from South Africas National Research Foundation (NRF) and Department of Science and Technology (DST), the Palaeontological Scientific Trust, and the Durand Foundation for Evolutionary Biology and Phycology.

Read the full paper entitled A new Heterodontosaurus specimen elucidates the unique ventilatory macroevolution of ornithischian dinosaurs on the eLife website.

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The Evolution of the Cruise Ship Safety Drill – Cruise Industry News

Posted: at 3:26 am

The pandemic is pushing for an evolution of the muster (safety) drill procedures on cruise ships.

To avoid gatherings of large passenger groups in confined spaces and maintain social distancing, the cruise lines are now reinventing the traditional process, using technology and other innovations.

Cruise Industry News has studied the new approaches taken by three major cruise lines.

Royal Caribbeans Muster 2.0

Royal Caribbean Groupannounced the replacement of the safety drill with Muster 2.0 in 2020.

The new program transforms the process originally designed for large groups of people into a faster, more personal approach that encourages higher levels of safety, the company previously said.

With Muster 2.0 guests will review safety information individually, using their stateroom TV or a smartphone before visiting their assigned assembly station, where a crew member will verify that all steps have been completed and answer questions.

Each of the steps will need to be completed prior to the ship's departure, as required by international maritime law.

In addition to Royal Caribbean Groups brands and joint ventures, the new Muster 2.0 may also be used by other cruise operators through licensing. Currently, patent licenses have already been granted to Norwegian Cruise Line Holdings Ltd. the parent company of Norwegian Cruise Line, Oceania Cruises and Regent Seven Seas Cruises.

Carnivals Hub App

Restarting service in July, Carnival Cruise Line recently revealed more details on its new safety drill procedures. The drills will now be divided into two parts, leaving the large-gathering safety briefings behind.

First, the guest will need to go to its muster station, using instructions received via Carnivals new smartphone app the Hub App. Crew members will be positioned around the ships to help guide the passengers. The crew will also make sure everyone visits their assembled muster stationsin the first hour and a half of being onboard.

The second part of the safety drills with Carnival is watching a safety video, which will be available in all staterooms and must be watched before the ship sails.

A protocol will be in place to control the attendance of the passengers in the new safety procedures. If a guest fails to complete the mandatory steps, he will be limited in what he can do on the ship.

While temporary for now, the new method may be implemented on a permanent basis if it proves to be effective and working, according to Carnival.

MSCs Safety Video

The first major cruise line to resume guest operations, MSC Cruises, has been in service in the Mediterranean since August 2020. To ensure social distancing during safety drills, the company has also changed its method.

Now, safety drills are carried out as soon as all the passengers board the vessel. To complete it, guests are asked to watch a five-minute video shown in their cabins and then head to their assembly stations.

At the muster points, a crew member scans each passengers cruise card, completing the process.

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