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Dr. Salari on family history, germline genetic risk in favorable-risk prostate cancer – Urology Times

In this video, Keyan Salari, MD, PhD, describes the background and notable findings from the recent Journal of Urology study “Impact of Family History and Germline Genetic Risk Single Nucleotide Polymorphisms on Long-Term Outcomes of Favorable-Risk Prostate Cancer.” Salari is a urologic oncologist at the Massachusetts General Hospital and Harvard Medical School.

Transcription:

Please describe the background for this study.

Prostate cancer, as you know, is a high disease burden condition. It’s the second leading cause of cancer death in the United States. But three quarters of patients who are diagnosed today are diagnosed with localized disease, many of whom have favorable prognosis that may not actually warrant treatment. But we know that there’s substantial clinical heterogeneity among patients with even low- or intermediate-risk prostate cancers. Many of the patients that we initially monitor with what we call active surveillance ultimately end up requiring treatment in the long run. There has been growing evidence that family history and germline genetic risk variants contribute to the risk of aggressive prostate cancer. And so in this study, we set out to investigate the impact of both family history as well as germline genetics in a cohort of patients with prostate cancer who had favorable prognosis as defined by standard clinical parameters.

What were some of the notable findings? Were any of them surprising to you and your coauthors?

One of the notable things just to describe about the cohort is that this is called the Health Professionals Follow-Up Study, which is a long-standing prospective cohort study run by the Harvard T.H. Chan School of Public Health. It started in the 80s, and the median follow-up for the patients with prostate cancer in the study is nearly 15 years, which is quite a long time and really allowed us to explore and look at a long-term important outcome, which is prostate cancer death, the likelihood of dying of prostate cancer. So we were able to look at the role of family history. And one of the things we did was not just limited to the family history of prostate cancer, but we also explored family history of breast and pancreatic cancer, other cancer types that we know are genetically related to prostate cancer. We had previously shown in one of our active surveillance cohorts at Mass General here that patients who have this expanded family history of prostate, breast, ovarian, or pancreatic cancer, have a higher risk of having progression of their disease on active surveillance with higher grade disease showing up on future biopsies. So we wanted to look at this more expanded definition of family history in the Health Professionals Follow-Up Study. And what we found is that over a third of patients, 36%, had positive family history of either prostate, breast, or pancreatic cancer. And if you had this type of a family history, there was nearly a two-fold risk of dying of prostate cancer in the long term. And each first-degree relative that you have with one of these family histories added about a 50% increased risk of dying of prostate cancer. That was one of the first notable findings. And then we moved on to start looking at germline genetic risk variants in the study. What we first looked at was something called a polygenic risk score, which is basically a score that aggregates the effect of many, many, many SNPs or single nucleotide polymorphisms, a common type of genetic variation in the human genome, that each individually may contribute only a small amount of risk, but in aggregate together can potentially confer a large risk on your risk of developing prostate cancer or dying of prostate cancer. What we found was that the most commonly used modern polygenic risk score that aggregates 269 different SNPs actually was not associated with prostate cancer death in our cohort. In some ways, this actually wasn’t a surprising finding, just because the initial era of polygenic risk scores were really designed from genome-wide association case control studies where the cases were any prostate cancer vs healthy controls. They weren’t really designed to distinguish aggressive prostate cancers from indolent prostate cancers. And so it wasn’t that surprising that this polygenic risk score in a cohort of our patients who all have prostate cancer didn’t distinguish those who died vs didn’t die. But there are newer polygenic risk scores that are being developed today that are in progress that are starting to look more closely at risk of aggressive vs indolent disease. And so after that, we started to drill down into some specific genetic variants that have been associated with prostate cancer survival, and we found 1 SNP on chromosome 19Q that was associated significantly with the risk of dying of prostate cancer—about an 80% increased risk if you had the risk allele. And then we looked together, combining that with family history and a multivariable model and found that family history and germline genetics – this specific germline genetic SNP—each independently increased the risk of dying of prostate cancer by about 80%. And if you limited the cohort to the patients with really low-risk disease, those that would be eligible for active surveillance under stricter criteria, it actually was almost a three-fold risk of dying of prostate cancer; the hazard ratio was 2.8. And so, it was quite interesting and just notable to see that both family history and this germline genetic risk SNP were independent contributors to that risk of dying of prostate cancer.

This transcription was edited for clarity.

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Apple reportedly using the best OLED panels for 2024 iPad Pro – 9to5Mac

OLED iPad Pro 4TB rumor (existing model shown)

It’s no secret by now that Apple will soon be announcing a new generation iPad Pro featuring OLED displays for the first time in both screen sizes. However, as the announcement nears, we now have more details about what to expect – and a new report claims that Apple is using the best OLED panels on the market for the 2024 iPad Pro.

2024 iPad Pro to use advanced OLED panels

Analyst Ross Young of Display Supply Chain Consultants (DSCC) has once again reported that the new iPad Pro models will indeed be equipped with OLED displays. However, Young was emphatic in saying that Apple has chosen the “best OLED tablet panels on the market” for its new tablets.

OLED panels use organic materials that emit light when an electric current is applied. These panels don’t need a backlight, unlike LCD displays, and each pixel is illuminated individually. This results in more contrast and deeper blacks, since the display can simply reduce the brightness or completely black out pixels in dark areas of the image.

However, OLED also has its downsides, such as reduced brightness compared to backlit panels and being susceptible to burn-in. When Apple brought OLED to the iPhone X in 2017, the company said it had addressed these concerns.

Young had previously said that the launch of the new iPads was partly delayed due to Samsung facing “technical challenges” with the production of these advanced OLED panels. It’s no surprise that Apple wants to have the best panels to show that the new technology is better than what it currently offers in the iPad Pro.

“The OLED iPad panels are expected to be by far the best OLED tablet panels on the market with LTPO, 120Hz refresh, a tandem stack and glass thinning resulting in ultra-thin and light displays with high brightness, extended battery life and long lifetime,” the analyst said in a note to investors.

What does that mean for consumers?

Apple OLED display panel — Phil Schiller on OLED displays

To make these displays brighter and also more efficient, Apple opted for panels with a two-stack tandem structure. This means that the display has two emission layers, which doubles the brightness compared to traditional OLED panels. The two-stack tandem structure panel also significantly increases the lifespan of the display, which is important for a product like the iPad.

Young also notes that OLED panels are much thinner than LCD panels due to the lack of backlighting. Rumors suggest that the 2024 iPad Pro models will be much thinner, which is probably due to the new display technology.

Apple currently uses a regular LCD panel in the 11-inch iPad Pro and a mini-LED panel in the 12.9-inch iPad Pro. For those unfamiliar, mini-LED uses multiple points of backlighting for increased contrast – but it’s far from reproducing perfect blacks like OLED. An OLED panel can also help save battery life in some situations.

Apple has set an event for May 7 to announce the new iPads.

More rumors on the new iPads

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International Audiences Drive ‘Fallout’ to Big Showing on Amazon – Hollywood Reporter

Fallout has become one of Prime Video‘s biggest series ever — according to Prime Video.

The well-reviewed show, based on the video game franchise of the same name, has become the second-most-watched title ever on the Amazon streaming service over its first 16 days of release, the company says. Prime Video says 65 million viewers worldwide have watched at least some of Fallout since its April 10 premiere, putting the show behind only The Lord of the Rings: The Rings of Power in the streamer’s catalog.

Global audiences have powered a majority of that viewing: More than 60 percent of Fallout’s audience is outside the United States. The (limited) data from Amazon jibes with that from outside sources like Samba TV, Luminate and Reelgood, all of which have tracked a strong start for the series (Nielsen’s streaming data lags by several weeks).

Prime Video has already renewed Fallout for a second season, picking up the series about a week after its premiere. At that time, the streamer said the show was among its top three titles to date.

Like the video game, Fallout is set some 200 years after a nuclear war and features a retro-futuristic design and heavy doses of dark humor. Season one focuses on three characters — a naive “vault dweller” (Ella Purnell) exploring the above-ground world for the first time; a warrior member of the Brotherhood of Steel (Aaron Clifton Moten); and an undead Ghoul (Walton Goggins). Moisés Arias, Kyle MacLachlan, Sarita Choudhury, Michael Emerson, Leslie Uggams, Frances Turner, Dave Register, Zach Cherry, Johnny Pemberton, Rodrigo Luzzi, Annabel O’Hagan and Xelia Mendes-Jones also star.

Geneva Robertson-Dworet and Graham Wagner created the series and serve as showrunners. They executive produce with Jonathan Nolan (who also directed the first three episodes), Lisa Joy and Athena Wickham of Kilter Films; Todd Howard of Bethesda Game Studios; and James Altman for Bethesda Softworks.

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Act Fast to Grab a Samsung Galaxy Tab S9 FE Plus for Only $500 – CNET

Samsung tablets have frequented our top tablets list pretty often. And right now on Amazon, you can get a decent discount on Samsung’s Galaxy S9 FE tablets, part of the company’s latest lineup. Prices are as low as $500 for the Plus version in the color silver, a $100 savings.

Those on the hunt for a new midrange tablet might want to consider Samsung’s Galaxy Tab S9 FE. It has an IP68 rating for water- and dust-resistance, making these tablets durable, and you can choose 128GB or 256GB of storage. The S9 FE standard tablet has a 10.9-inch display, and the S9 FE Plus version has a display that’s a bit bigger at 12.4 inches.

You likely won’t have to worry about your tablet running out of juice while you’re using it, as you’ll get battery life of 18 hours for the S9 FE and 20 hours for the S9 FE Plus. Both versions have an 8-megapixel camera, allowing you to take better pictures than previous models were capable of. The two versions of this tablet also come with the Galaxy Connected Experience feature, which lets you use the tablet to take calls and messages sent to your Galaxy phone.

If the Galaxy Tab S9 FE or S9 FE Plus models aren’t exactly what you were looking for, check out our roundup of the best tablet deals currently available.

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