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  • Norwegian Olympic medalist Audun Grønvold dies after lightning strike | Skiing

    Norwegian Olympic medalist Audun Grønvold dies after lightning strike | Skiing

    The 2010 Olympic ski cross medalist Audun Grønvold has died after being struck by lightning, the Norwegian ski federation announced on Wednesday. He was 49.

    Grønvold won bronze at the 2010 Vancouver Games.

    “It is with great sadness that we have received the news of Audun Grønvold’s untimely passing,” the federation said. “The former national alpine skier and ski cross athlete was recently struck by lightning during a cabin trip.”

    The federation said Grønvold was “quickly taken to hospital and received treatment for the injuries he sustained in the lightning strike” but died on Tuesday night.

    Grønvold was a member of Norway’s alpine skiing team before he moved into freestyle and ski cross. He had one podium finish as a World Cup alpine skier, finishing third in a downhill in Sierra Nevada, Spain, in 1999.

    He also won a bronze medal in ski cross at the 2005 world championships, and the overall ski cross cup in 2007. After his career ended, he became a national-team coach and a TV commentator.

    “Norwegian skiing has lost a prominent figure, who has meant so much to both the Alpine and freestyle communities,” the federation president, Tove Moe Dyrhaug, said, adding that his death created “a huge void”.

    Grønvold his survived by his wife and three children. His wife, Kristin Tandberg Haugsjå, said in a Facebook post that her husband was “my great love and my best friend for 20 years”. She added the accident had happened while they were on their summer vacation.

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  • King Charles’ love for Kate Middleton reaches new heights: ‘Sends him care packages’

    King Charles’ love for Kate Middleton reaches new heights: ‘Sends him care packages’

    King Charles and Kate Middleton mark a monumental milestone in their bond

    King Charles’ love for his daughter-in-law and future Queen Kate Middleton has been revealed once more.

    The news this time around has come from a well placed source, that just sat down with Heat World.

    According to their findings, “The King has always respected Kate,” right from the beginning of her marriage to Prince William.

    Not to mention “he sees her as the glue that holds the family together,” the insider also admitted.

    A big reason for that is because he thinks she’s “level-headed” as well as “intelligent.”

    Even her “compassionate approach to life is hugely inspirational,” to the monarch the source admitted.

    For those unversed the “Admiration is mutual” too. “Kate looks up to Charles and is proud to be one of his most trusted confidants.”

    Near the end the source also explained that cancer was also a big part in bringing them closer together. “They are a big source of strength to each other,” the source revealed as well. “Kate sends him care packages, which means so much to Charles.”


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  • GBH Drama recaps The Gilded Age Season 3

    GBH Drama recaps The Gilded Age Season 3

    As drama fans, it’s honestly kind of wild that we are just now talking about The Gilded Age for the first time. And yet, here we are. Season 3 is currently airing, and now that we’ve reached the midpoint (and an episode with some MAJOR plot developments, which yes, we will be discussing; spoilers ahead) it’s time for GBH Drama to talk over everything that’s happened so far this season: the good, the bad, and the dramatic.

    Jackie: To kick things off: can we talk about this new Ada vs Agnes dynamic? It honestly feels like less of a contest than it should; technically, there’s a clear winner in Ada, but she’s been such a pushover for so long it’s hard to re-conceive of her as the one in charge. Now I sound like Agnes, lol.

    Amanda-Rae: Hahaha, you kinda do sound like Agnes! Although Ada’s crusade is annoying, it’s a good thing for the audience to see that the Temperance movement in the pre-Prohibition context of other social reform movements: settlement houses, suffrage, etc. They missed the fact that complete poverty or self-medication for mental illness were the main root causes for these issues, not individual religion/ethics. In addition, Temperance activists were angry at many recent immigrants for bringing either pub culture and/or Catholic and Jewish religious rituals with wine into mainstream American culture. You can see these threads between the lines at the meetings.

    J: I actually kind of hope they go a little deeper into the Temperance movement as the season goes on. I think because of the way we talk about the impacts of Prohibition (with the benefit of hindsight) it’s easy to forget that alcohol was — and is — a huge driver of violence against women, and in an era where it’s next to impossible to get away from a bad marriage, or control your shared finances, that quickly becomes much more serious than “people should be allowed to have wine at dinner.” Between that and the xenophobia you mentioned, there’s a lot of rich plot to explore!

    Speaking of plots to explore more: I want Peggy to be happy so much, and a cute doctor might be a real win. But his mom’s colorist attitude is concerning.

    A: Phylicia Rashad is a Black Hollywood Legend and she usually plays heroines, so it’s been wild for me to dislike Elizabeth so much. I knew immediately Elizabeth was not going to like Peggy for her son. I do hope the good doctor will eventually tell his mother to back off. Peggy and William are so cute together, and the cliff walk was so romantic!

    Phylicia Rashad as Elizabeth Kirkland


    Courtesy of HBO

    J: SO romantic! And Peggy deserves a nice romance! Speaking of Dr. Kirkland’s parents/acting legends, I’m constantly delighted by the Broadway talent on this show, but it was particularly fun to see Brian Stokes Mitchell and Audra McDonald on screen together because I’ve had Ragtime on the brain since the Stanford White cameo back in season one. They are both SO good in that show, and obviously there’s a lot of thematic overlap. Anyway, as ever, I am delighted at how much The Gilded Age casting department loves to bring in heavy-hitter theater people!

    A: The Gilded Age casting department has worked on several Broadway shows so they pride themselves on giving Broadway actors the chance to do something great in between shows. In addition it’s been noted in earlier season cast/crew interviews that The Gilded Age bailed out many actors who were out of work when Broadway was closed due to COVID restrictions.

    J: Yet another reason to stan the casting team. Such a great choice. Kind of a pivot here, but before we get into the details of episode four, we should check in on some of the other major storylines this season. How do we feel about George’s business ventures this time around?

    A: George’s vision of getting into freight railroads is forward-thinking in terms of what we know about technology today, but we also know these mines are on land that was likely stolen from various Native American tribes and groups. Also we know this also comes at the cost of exploitation. This part of his character is easy to dislike. However we also know that he has to pay for Glady’s wedding so he has to succeed. The bad parts of his character are definitely balanced out a bit by the fact he does care about Bertha and the kids so much.

    J: Look, I think we have to admit that George (and all the real-life guys that he represents) is a bad dude overall. These industrialists did make major improvements to American infrastructure, but at the cost of the health, happiness, and safety of their workers. His money is earned on the backs of a lot of people who never got to benefit in a real way from their labor. All that being said: George is probably my favorite character on the show. He’s much more compelling to me than a lot of his contemporaries because he’s got a code and he sticks to it. And I love a male character who clearly respects and values the women in his life. I fear that he might have bitten off more than he can chew with this latest project… but such is the price of boundless ambition.

    A: George is definitely on thin ice, these mine owners and his competitors can easily switch up their tactics and leave him broke.

    J: Speaking of switching up tactics: we have to talk about Aurora’s husband. I thought he was cool! What a horrible reversal! It sucks that she’s being punished for his bad behavior, and I think this is another good reminder that there’s a reason so many of the older women in the show are SO particular about marriages. The idea that you can be doing great for that many years and then lose everything because your husband decides he’s bored, or that you might end up married to a monster like Agnes, or in a permanent separation situation like Mrs. Astor, would make me VERY concerned about the decision-making of any younger female relative.

    A: That “come outside we’re not going to jump you” meme immediately comes to mind for Charles Fane. Half the fandom wants him killed off, and I don’t blame them. He’s being horrifically selfish, and unlike today, Aurora has no power to fight him in court. I agree with you that Bertha’s opinions about Gladys’ suitors makes so much more sense in this context.

    J: And on that note: re: Bertha’s pushiness about the Duke, I don’t like it, but I get it! My very unkind opinion is that Gladys is not a very interesting person, unlike both of her parents, and so I don’t find it that surprising that her VERY intense mother is like… not that interested in what Gladys wants. Gladys very rarely has strong opinions about anything.

    A: I like Gladys but she’s clearly adapted to Bertha’s extremely strong personality via being reserved. I loved her tender moments earlier this season with Larry though, they have such a strong sibling bond. Were you surprised that Gladys went through with marrying the Duke?

    J: Mostly no, although Gladys DID look like she might do a runaway bride for a hot minute there. I just honestly can’t imagine her being bold enough to go against her mom, especially after George was like “you don’t technically have to get married, but let’s be real, it’ll really suck for everyone if you back out.” Also, her new husband is hard to pin down: I think if he seemed really evil and scary I’d have been more inclined to think Gladys would find a way out of the marriage, or George would have tried harder to stop it. I don’t think for a second that that would change anything for Bertha, to be clear. Once she gets a plan in her head there’s no turning back.

    A: I guessed as soon as Season 2 ended that Bertha was going to make the match no matter what. I agree, if George got bad vibes from the Duke, he would have paid him off to go away. Bertha had too much time when he went to Arizona to scheme and make legal promises. Gladys, before the marriage, also didn’t seem headstrong enough to fight after her running away attempt failed. She was, of course, sad that she was leaving everything she knew behind, but we’ll have to see how the Duke treats her. What do you think is behind the Duke’s Stiff Upper Lip?

    J: GOOD question. I honestly wonder how much of his behavior is that he’s not that into marrying Gladys either but really really needs her money? Unfortunately for Ben Lamb, who has been in a lot of things that I like (Endeavour! Victoria!), he is most recognizable from his turn as the Christmas Prince, which is not a film anyone’s going to be defending as high art any time soon. I want him to bring a little bit more to this role, because so far it’s really hard to figure out exactly what kind of guy he is. While I dislike that the Duke is so uncool about George wanting to give Gladys some of her own money, he’s not obviously, mustache-twirlingly evil either? He’s kind of a non-entity. His sister, on the other hand, I am more worried about. She was fairly unpleasant and, dare I say it, a little overly invested in keeping her brother all to herself?

    A: I definitely spotted Ben Lamb from his past roles in Victoria and Endeavour as well! I believe he’s not actively evil but at the same time not presenting himself as a very warm and friendly person. I sensed when I first watched this episode that the Duke’s sister is probably not happy that Gladys can now tell her what to do. I got the vibe she’s either single or a widow. We’ve seen this family structure in MASTERPIECE dramas before, such as Poldark, where Elizabeth displaced Verity as the lady of Trenwith House. I’m sure future episodes will follow what happens next.

    J: Very good point. I really hope we get more info on whatever’s happening with them, especially since they’re SO far away from the rest of the action.

    Taissa Farmiga as Gladys Russell and Ben Lamb as the Duke of Buckingham

    Taissa Farmiga as Gladys Russell and Ben Lamb as the Duke of Buckingham


    Courtesy of HBO

    A: Is Bertha a villain, technically?

    J: Probably, but I kind of don’t care? I love her. We so rarely get to see ambitious nightmare women on screen, and her commitment to being extremely ruthless is a nice balance to the younger female characters in this show in particular. Also, you get what you expect with Bertha. I wouldn’t want to be her daughter, or her rival, but at least you know exactly what she’s going to do at any given moment, which makes her a lot easier to coexist with (if you’re willing to play the game too, which is why Gladys’ situation is kind of a bummer; she doesn’t even know she’s playing a game).

    A: I love that Bertha is truly a complex female character. Fans want that as a concept but then they don’t like it when they actually see women living in grey areas. It’s too easy to call Bertha a villain by modern standards. I genuinely believe she thinks this marriage was the best decision for Gladys because her future would be secure, and she would influence society, not just be a housewife. She didn’t trust Gladys’ other suitors and it’s understandable because Gladys would be a prime target for fortune hunters.

    J: Facts. While we’re talking about the Russells, let’s chat about the guys. Much the same way that I love Bertha even though she’s a little vilainous, I also love George. I think he did the best he could to help Gladys out in this episode, and I don’t want to take away what little agency she has by arguing that she didn’t have a choice in the matter.

    A: In terms of George with his family, he’s far more likable. Bertha made it hard to keep his promise to Gladys. He’s invested in Gladys and Larry’s lives in a way that’s rare for someone of his class.

    J: Larry inviting his aunt to the wedding is one of the more interesting things he’s done; love that chaos energy, hope he keeps it up. It was fun to see him channel his parents a bit during the clock negotiation too. Speaking of the clock stuff, what a fun interlude? Since the show talks such a big game about the accessibility of the American dream, it’s nice to see that actually reflected with Jack. Also I just actually looked up that deal on an inflation calculator and holy smokes; man just walked away with a cool $9.5 MILLION. That is an unhinged amount of money!

    A: I love Larry so much this season. Inviting the aunt they don’t talk about because it would reveal Bertha isn’t a WASP was a lovely bit of chaos. Larry helping Jack is a fun interlude between all of the serious plot lines as well.

    Audra McDonald as Dorothy Scott and Denée Benton as Peggy Scott

    Audra McDonald as Dorothy Scott and Denée Benton as Peggy Scott


    Courtesy of HBO

    J: Speaking of serious plot lines… Peggy is such a cool character; she’s for sure the most interesting person on the show in my opinion. I very much dislike how much awful stuff keeps happening to her! I just want her to be happy and get some peace! She deserves both professional success AND personal happiness.

    A: Agreed, Peggy has been my fave character since the beginning. You can see just how much care the creative team has taken to make sure we see Black lives after the Reconstruction Era. I’ve interviewed the cast and crew about next week’s episode in particular so I’m excited for everyone to see what’s next for her!

    J: It’s a real breath of fresh air that the show has made an opportunity to talk about race (especially in terms of what would be realistic in this era) and really embraced that; I feel like that’s a nice evolution from Downton Abbey, which had a few storylines covering class and gender, but to my memory didn’t touch on race at all.

    A: It’s funny you mention that because Julian Fellowes in his own way took those critiques about Downton Abbey and conducted his own research into this era. The very first version of The Gilded Age plot line that was publicly released nearly a decade ago had Peggy as a servant, and we’ve obviously moved far away from that thanks to the historical consultant Dr. Erica Dunbar.

    J: While we’re talking about Downton… The Duke bagging a rich heiress to save his probably bankrupt estate sure did feel familiar. Hopefully, for Gladys’ sake, the two of them come to have a nice relationship like the Crawleys! Beyond that, what are you looking forward to for the rest of the season? I personally can’t wait for Agnes to find out about the clock money. She’s gonna lose it. I’m also excited, as ever, for more costumes and sets; half of watching this show is me pausing to admire one of the dresses. Speaking of which: you mentioned to me that you were working on a cosplay for this… can you tell us a little bit about the project?

    A: I’m sure Agnes is going to crash out about the clock money! Yes, the cosplay is technically finished but it’s a spoiler for a future episode so I haven’t posted too much about it.

    J: Can’t wait to see it! I think stuff is gonna get messy between Bertha and Mrs. Astor, just based on that interaction at the wedding. I think Bertha’s sister is going to stick around and cause trouble. Not so much for Bertha, honestly, although I do think that’s a fun tension to explore — I think Mrs. Winterton/Turner is going to have a really hard time resisting the urge to poke around there, which might bite her in the ass.

    A: Those are good predictions. I’m also going to predict that we’ll see another scene like the cliff walk from Peggy and William, and get an update about Gladys and the Duke. I’m also really hoping we see more of Pumpkin. I miss seeing him snuggled up with Ada. Did he refuse the temperance pledge? 😉

    J: An incredible question, and one I really hope we get an answer to soon. Obviously there’s still the rest of the season ahead of us, and if folks are looking for even more Gilded Age goodness, make sure to check out our American Experience documentary on the real story of this era. The full documentary is free on YouTube right now and also streaming on GBH Passport.


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  • Threads is testing Facebook account sign-ups

    Threads is testing Facebook account sign-ups

    Threads is testing letting you sign up with a Facebook account rather than an Instagram account. The new option, spotted by Social Media Today, doesn’t appear to be widely available yet, but is already mentioned in a Meta support article.

    Besides making it easier for people who don’t have an Instagram account to quickly create an account on Meta’s X and Bluesky competitor, this new Facebook sign up option should influence the kind of posts and ads that get recommended to you.

    “Signing up to Threads with your Facebook account helps unlock features that work across Threads and Facebook, like using the same login info to access both apps,” Meta writes in a support article. “If you create a Threads profile with your Facebook account, we’ll combine your info across Threads and Facebook.”

    Encouraging users to build their Threads profile using the information and followers they had on Instagram was one of the ways Meta quickly grew its Threads user base. It hasn’t always led to the best experience on Threads, though. As it turns out, growth-obsessed Instagram users produce fairly shallow text posts. And because most people’s Instagram accounts are associated with their Threads profile, they get served a lot of that subpar engagement bait by default. If you came to Threads looking for the relative wit of X, you’d come away pretty disappointed.

    Letting you sign up with Facebook will likely have its own shortcomings (namely, modern Facebook is pretty spammy, too), but it at least acknowledges that what people want from Instagram is different from what they want from Threads.

    Meta has made a concerted effort as of late to establish Threads as more of an independent entity. Adam Mosseri, the head of Instagram at Meta, shared that the company planned to remove “the Instagram graph import from the onboarding flow” back in November 2024. Threads also started testing using its own separate direct messaging inbox in June, after relying on Instagram DMs since launch.


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  • Tailoring CLL Treatment with BTK Inhibitors in a Community Setting

    Tailoring CLL Treatment with BTK Inhibitors in a Community Setting

    Treatment-naive chronic lymphocytic leukemia (CLL) requires careful consideration of efficacy, safety, and patient-specific factors when selecting initial therapy. The discussion was moderated by Dr. Andrew H. Lipsky, an assistant professor at Columbia University Medical Center and hematologist/oncologist at Columbia University Herbert Irving Comprehensive Cancer Center, alongside community oncologists in North and South Carolina at a virtual Case-Based Roundtable. The group debated the use of Bruton’s tyrosine kinase (BTK) inhibitors such as acalabrutinib (Calquence) and zanubrutinib (Brukinsa) vs venetoclax (Venclexta)-based regimens, weighing factors such as dosing flexibility, tolerability, and fixed-duration therapy preferences.

    Join a Case-Based Roundtable near you—register today!

    DISCUSSION QUESTIONS

    • Considering the data for acalabrutinib, zanubrutinib, and venetoclax, how do you interpret the efficacy and safety data and use it in your practice?
    • What is the balance between efficacy and safety that leads you to choose between available treatment options?

    Margaret Howard, MD, MSc: In terms of the acalabrutinib study [ELEVATE TN; NCT02475681] looking at acalabrutinib alone vs addition of obinutuzumab [Gazyva], I have to give that thought with regard to the specific patient population and their comorbidities and such. But I am definitely inclined based on the burden of disease to do 2 agents in that setting.

    Andrew H. Lipsky, MD: Have you ever given obinutuzumab with acalabrutinib? Or is that just single-agent acalabrutinib?

    Charles Kuzma, MD: Always as a single agent.

    Lipsky: Do you have any opinions about obinutuzumab, or those data?

    Kuzma: I'm intrigued by the data with the progression-free survival benefit,1 but a lot of times patients vote for that as compared with the BCL-2 because it doesn't contain intravenous therapy, and the convenience of it practicing here in a rural setting. The more recent trial did demonstrate an OS benefit with the addition of it, so I try to keep it simple.2

    Rajesh Bajaj, MD: I generally give acalabrutinib alone.

    Lipsky: We find that [makes sense]. I have given plenty of acalabrutinib in my day as well, and the number of times I've given it with obinutuzumab is only once. Sometimes people might say if you have someone with hemolytic anemia or autoimmune cytopenia and it's not well controlled, then you need an anti-CD20 or you need rapid debulking, maybe you might do that.

    What do you think about the safety of BTK inhibitors in general?

    Viral Rabara, MD: I think all of these BTK inhibitors are so good. I think a lot of the patients don't even need a full dose to get the effect in CLL. I rarely run into any major adverse events [AEs] with the BTK inhibitors, especially with lowering the dose initially.

    Lipsky: Have you started a BTK inhibitor in the last 6 months at a lower dose than the initial label dose? Why did you do that, and who's the kind of patient you would do that for? I've also done that, but what made you think to do that?

    Rabara: A lot of it also depends on if the patient is found to have CLL and is not very symptomatic, or if they're old and have lot of comorbidities. I practice in a rural part of the country, so a lot of the patients are also hesitant about taking all these drugs. Instead of scaring them away with the possibility of AEs at a higher dose, I'll start them lower, and if I need to, I'll slowly titrate it up. I haven't had to do titration up on the majority of the patients.

    Lipsky: If you're doing zanubrutinib, are you starting at 2 pills or 1 pill?

    Rabara: I'll start off at 1 pill.

    Matthew S. McKinney, MD: We've had a couple of 90-year-old or older patients where that was just the plan. There are not high-level data. Zanubrutinib, especially if you can do 2 pills just once a day, is probably as good as acalabrutinib or ibrutinib [Imbruvica] in terms of BTK inhibition with the data we have. Whether that changes the AE profile, we don't know. But sometimes I'll start low and then try to increase or start low and keep it there if the disease is controlled.

    Alexandra Stefanovic, MD: I think most of us at Duke Cancer Center prefer the BTK inhibitors in the first line, and that has to do with the fact that a lot of our patients come from far away. The logistics of using venetoclax are very difficult practically. The BTK inhibitor is easy to prescribe, and with zanubrutinib, we can titrate if there are AEs, such as diarrhea; one can easily go down to 1 or 2 capsules per day and either keep it at the lower dose or go back up when AEs subside. It's relatively more easily managed. With venetoclax, with the cytopenias, it is a little bit more difficult to titrate. Not everybody tolerates the full dose there, and that's a little bit more challenging.

    Lipsky: Who's your ideal venetoclax/obinutuzumab patient, where you might move away from the BTK inhibitor, if you had to?

    Stefanovic: I think the ideal venetoclax/obinutuzumab patient is somebody who lives close enough, but also from the risk profile has no TP53 mutation or deletion, and who wants the time-limited approach, who doesn't want to be taking medication on a daily basis for the rest of their lives. So that idea is sometimes predominant for patients. We do work with patient preference.

    Lipsky: Dr Madadi, what about your practice with BTK inhibitors? Are you an acalabrutinib or zanubrutinib person, what's your preference there?

    Anusha R. Madadi, MD: Mostly zanubrutinib, [because it is] better tolerated, and also you could do once daily for patients who find twice daily an issue. I've also done mostly venetoclax/obinutuzumab, because in younger patients, sometimes they just prefer the limited duration. They don't want to be on a pill forever, unless there are high-risk features.

    Join a Case-Based Roundtable near you—register today!

    DISCLOSURES: Lipsky previously reported consultancy, membership on an entity's board of directors, or advisory committees with Abbvie, Loxo-Lilly, Synthekine, Beigene, and AstraZeneca.

    References:

    1. Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Lancet. 2020;395(10232):1278-1291. doi:10.1016/S0140-6736(20)30262-2

    2. Brown JR, Seymour JF, Jurczak W, et al. Fixed-Duration Acalabrutinib Combinations in Untreated Chronic Lymphocytic Leukemia. N Engl J Med. 2025;392(8):748-762. doi:10.1056/NEJMoa2409804


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  • More Than Maple Syrup: Foreign Bank Opportunities in Canada | Insights

    More Than Maple Syrup: Foreign Bank Opportunities in Canada | Insights

    In this webinar, the Mayer Brown team will be joined by Torys LLP to discuss the ways in which US and other foreign banks can engage in business in Canada.

    Canada has a vibrant economy and abundant natural resources that present opportunities for global corporates and financial institutions. It is one of the United States’s largest trading partners, with over $2.5 billion in goods and services crossing the border each day. Over $110 billion in assets sit in the Canadian bank subsidiaries and branches of US banks.

    US and other foreign banks have been permitted to own banking subsidiaries in Canada since the 1980s and there are no restrictions on foreign ownership of shares in domestic Canadian banks. Today, Canada’s bank regulatory requirements apply equally to all banks in Canada regardless of their ownership structure or whether the bank is owned by Canadians or non-Canadians. However, there remains a perception that foreign banks are not welcome in Canada.

    This webinar will explore the legal framework for foreign banks to engage in business in Canada and address some of the misunderstandings about the functioning of the Canadian banking sector.

    CLE credit is pending.

    Monday, July 28, 2025

    United States
    12:00 p.m. – 1:00 p.m. EDT
    11:00 a.m. – 12:00 p.m. CDT
    10:00 a.m. – 11:00 a.m. MDT
    9:00 a.m. – 10:00 a.m. PDT

    Europe
    5:00 p.m. – 6:00 p.m. BST
    6:00 p.m. – 7:00 p.m. CEST

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  • FDA Grants Fast Track Status to ZEN-3694 Plus Abemaciclib for Unresectable or Metastatic NUT Carcinoma

    FDA Grants Fast Track Status to ZEN-3694 Plus Abemaciclib for Unresectable or Metastatic NUT Carcinoma

    The FDA has granted fast track designation to ZEN-3694 for use in combination with abemaciclib (Verzenio) for the treatment of patients with unresectable or metastatic NUT carcinoma who have received at least 1 prior line of chemotherapy.1

    The agent is currently under evaluation in a phase 1 trial (NCT05372640) in combination with abemaciclib in adult and pediatric patients with unresectable or metastatic NUT carcinoma, breast cancer, and other solid tumors.2

    “We are thrilled that the FDA has recognized the strong potential of ZEN-3694 in benefiting patients with NUT carcinoma, an extremely aggressive, deadly cancer, for which there are no effective or approved treatments,” Donald McCaffrey, president and chief executive officer of Zenith Epigenetics, stated in a news release.1 “Fast track designation will accelerate ZEN-3694’s clinical NUT carcinoma program by expediting its development and review, and allow us to deliver this potentially life-saving drug to patients sooner.”

    Mechanistic Rationale

    In NUT carcinoma, the NUTM1 gene is fused with a transcriptional regulator such as a BET protein in most cases, driving expression of cancer-causing genes. This leads to unregulated growth of tumors.

    ZEN-3694 is a potent, selective, orally administered BET inhibitor that interrupts the activity of the NUT fusion protein, which has translated to antitumor activity alone and in combination with abemaciclib in NUT carcinoma. Notably, the combination of ZEN-3694 and abemaciclib has shown improved responses compared with BET inhibitors alone by inhibiting common resistance mechanisms. The agent has also proven tolerable with long-term use, showcasing a favorable adverse effect profile.

    Trial Enrollment Criteria, Design, and Objectives

    To be eligible for enrollment in the phase 1 trial individuals must be at least 12 years of age or older with a histologically confirmed malignancy that is unresectable or metastatic and for which standard curative or palliative interventions do not exist or are ineffective.2 Patients could have received any number of prior lines of therapy in the metastatic setting, including prior BET inhibitor therapy and prior CDK4/6 inhibitor therapy. Additionally, any acute effects from prior chemotherapy and/or radiotherapy must have resolved. An ECOG performance status of 2 or below was also required for patients at least 16 years of age and a Lansky score of at least 50% was required for patients under 16 years of age.

    Patients with treated brain metastases are eligible if there is no evidence of progression on follow-up brain imaging after central nervous system–directed therapy and disease has been clinically stable for at least 1 month. Notably, patients must be able to swallow oral medications.

    Eligible patients received ZEN-3694 once daily on days 1 through 28 or 5 days on and 2 days off, plus oral abemaciclib twice daily on days 1 through 28 of each 28-day cycle. Treatment will continue until disease progression or unacceptable toxicity.

    The primary outcome measures include defining the maximum-tolerated dose or recommended phase 2 dose of ZEN-3694, the incidence of AEs, overall response rate, clinical benefit rate, and duration of response. Additional parameters with which investigators are using to define efficacy include time to response, overall survival, and progression-free survival. Secondary objectives include pharmacokinetic and thymidine kinase assessment.

    The developer of the agent, Zenith Epigenetics is also seeking orphan drug and breakthrough therapy designations for ZEN-3694 in NUT carcinoma.1

    References

    1. FDA grants Zenith’s ZEN-3694 fast track status. News release. Zenith Epigenetics. July 14, 2025. Accessed July 15, 2025. https://www.zenithepigenetics.com/newsroom/news-releases?article=63
    2. Testing the safety and efficacy of the combination of two anti-cancer drugs, ZEN003694 and abemaciclib, for adult and pediatric patients (12-17 years) with metastatic or unresectable NUT carcinoma, breast cancer and other solid tumors. ClinicalTrials.gov. Updated April 9, 2025. Accessed July 15, 2025. https://clinicaltrials.gov/study/NCT05372640?term=bromodomain%20inhibitor&viewType=Table&rank=7

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  • How Family History Distinguishes Bipolar Depression From MDD, With Gerald Maguire, MD

    How Family History Distinguishes Bipolar Depression From MDD, With Gerald Maguire, MD

    Gerald Maguire, MD

    Credit: University of California, Riverside

    At the 2025 Southern California Psychiatry (So Cal Psych) Conference from July 11 – 24 at Huntington Beach, California, Gerald Maguire, MD, director of the residency training and chair of psychiatry at the College Medical Center in Long Beach, California, presented on how to detect bipolar depression from major depressive disorder (MDD). It comes down to 1 thing: family history.

    Maguire is also the founder and president of the Stuttering Treatment and Research Society (STARS), a non-profit organization that has raised over $10 million to help people who stutter and raise awareness for this neurological condition. In this interview, Maguire shared how to differentiate bipolar depression from MDD, causes and treatments for agitation, and how to treat anxiety or depression caused by stuttering.

    HCPLive: Today at the conference, you’re talking about the difference between bipolar depression and MDD. Can you tell our audience how they tell the difference?

    Maguire: The key is cross-sectional. When you see someone and they’re depressed, you can’t tell necessarily. I wish in psychiatry we had blood tests or biomarkers, but [it] wouldn’t be as much fun.

    The best way we differentiate is by history, and sometimes not just from the patient, but from the family members or others around them. We look longitudinally back; if there’s ever been a history of mania, then this depressive episode that we’re looking at now would be a bipolar I depression. If there’s history of only hypomanic episodes, and now we’re looking at a depressive episode, then that would be bipolar 2 depression.

    There are certainly other clues in our diagnostic schema. One, if a patient has had a… misadventure on an antidepressant, if they’ve been prescribed an antidepressant and they got worse, they got more agitated…that may be a clue that what you’re dealing with is a bipolar depression. If there’s a family history, unfortunately, of people passing from suicide, that may be a clue as well, and even sometimes coexistent substance use that patients with bipolar may, at times, self-medicate. It’s important to look into these other co-existing factors that may give us clues that this is a bipolar depression, as opposed to a major depressive episode of major depressive disorder.

    HCPLive: Once you’ve made that determination, what kind of treatments are you going to consider?

    Maguire: We tailor our therapies based upon the diagnosis. One thing I’ve always tried to teach my residents, if your known treatments aren’t working, is a diagnosis correct? Sometimes [after] 3 or 4 antidepressants… patients aren’t responding, or they’re getting worse. Is it really major depressive disorder? That’s 1 clue.

    Keep in mind that not many agents are approved for bipolar depression. Most of our agents that we talk about as mood stabilizers may be effective in preventing a manic episode or treating mania or mixed states. Our options are more limited when it comes to bipolar depression, and we do have some agents that are FDA-approved specifically for bipolar depression.

    HCPLive: You’re also talking about agitation and dementia, which has been a big topic lately, right?

    Maguire: With agitation and dementia, our hands have been really tied as clinicians, because unfortunately, for years, patients [were] getting older, and we had nothing FDA approved to treat them. If anything, agents we were using were given a box warning not to use about the risk potentially of increased mortality, cerebrovascular adverse events with antipsychotic agents in patients with agitation associated with dementia.

    Fortunately, we have one agent that is on label now, and that’s been FDA approved for the treatment of patients with agitation associated with dementia due to Alzheimer’s. It’s nice to know that we have that option. Fortunately, it appears that we may have other options, BFD approved in the fairly recent future.

    HCPLive: Could there be something that’s leading to the agitation? Has a patient, say, had a change in environment?

    Maguire: When we change the environment [of patients with dementia], they may become more restless, more agitated. Look for other things that could be leading to it. For instance, a co-morbid medical condition. Perhaps they have a urinary tract infection. Maybe this is a delirium, that there’s some drug interaction [playing] a role. Maybe there’s a slight infection, maybe there’s a metabolic issue. So, before we go adding on another medicine, make sure that we know medically what’s also going on for that patient. Make sure our patients are not in pain before we add something else [to the] board.

    HCPLive: What’s the long-term prognosis and treatment strategy for someone with agitation dementia?

    Maguire: Right now, we have data that shows that we can treat this acutely. We do know that agitation, in and of itself, leads to a poor prognostic outcome for patients with dementia. We know our goal is to keep our patients in the least restrictive, most supportive environment we can. The longer we can keep them at home, surrounded [by] their family members, the better. The key is preventing those agitation episodes and treating them allows these individuals [to] have a better quality of life and to spend more time with their loved ones.

    HCPLive: For patients who come in and see a psychiatrist, maybe they are dealing with depression and anxiety as a result of their stuttering. What can psychiatrists do to help?

    Maguire: It’s so important because [among] people [who stutter], over 80% may struggle with social anxiety. We also know that it’s coexisting. Stuttering is a basal ganglia condition.

    The key [is] to understand what treatments may make the underlying stuttering worse, and how best we can treat the underlying depression and anxiety, and attention issues. It’s going to be a comprehensive approach, understanding we’re developing, hopefully, newer treatments, that can help the core features of stuttering and then work toward cognitive behavioral and other forms of therapy, and even agents to treat the social anxiety or treat with the ADHD or the obsessive compulsive symptoms without worsening the underlying stuttering.

    HCPLive: Anything else that you want to talk about this, or anything else in psychiatry that you think is important for readers?

    Maguire: Well, I think what’s important for individuals that psychiatry…is [often] misunderstood because we’re dealing with really the most complex organ system, and that’s the human brain. It’s more difficult to understand than, say, the heart, the kidney.

    As we learn more about neuroscience, the understanding will grow among healthcare professionals, and compassion will grow. We need better targeted treatments, and they’re going to be personalized, not one size fits all, and so the diversity of what we see in psychiatric conditions will require that diverse treatment approach as well.

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  • Copilot is coming to cars — and so are Teams calls

    Copilot is coming to cars — and so are Teams calls

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  • Sabrina Carpenter Is Living La Dolce Vita—With Vacation Style to Match

    Sabrina Carpenter Is Living La Dolce Vita—With Vacation Style to Match

    Following the globe-spanning Short n’ Sweet tour and ahead of her forthcoming album, Man’s Best Friend, Sabrina Carpenter is on a well-deserved vacation. The singer jetted off to Italy, where—to nobody’s surprise—she brought a fabulous, La Dolce Vita-inspired wardrobe to match.

    For an itinerary that consisted of lounging on balconies, drinking goblet-sized spritzes, eating bowls of pasta, and petting stray cats, Carpenter brought along whimsical summer staples: minidresses, bikinis, bloomers, and matching sets galore. Like her tour wardrobe, the singer embraced a delicate color palette, mainly sticking to white, baby pink, and butter yellow, but every so often she punctuated her pastels with sporadic splashes of black and red.

    Courtesy of @sabrinacarpenter on Instagram

    Lightweight pieces were central to Carpenter’s Euro summer wardrobe. (Because, when forgoing air conditioning…) See: the open knit off-the-shoulder long-sleeve she wore over a polka-dot bikini top, and the semi-sheer black and white minidress she paired with a black newsboy cap.

    Image may contain Sabrina Carpenter Clothing Hat Accessories Jewelry Ring Adult Person Bag Handbag Head and Face

    Courtesy of @sabrinacarpenter on Instagram

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