Category Archives: Progress

Two new innovations could make it easier for doctors to decipher when cancers that impact women are present and need urgent attention:

As part of a leading translational research team, it is gratifying and exciting to see the movement of science toward innovations with actionable information that can guide treatment decisions, said Richard Moore, M.D., chief of the division of Gynecological Oncology and director of the Targeted Therapeutics Laboratory at Wilmot.

Richard Moore, MD

Liquid Biopsies Could Simplify Metastatic Breast Cancer Detection

Last month, the U.S. Food and Drug Administration granted a United Kingdom-based company, ANGLE, the first-ever product clearance for technology called the Parsortix PC1 Clinical System. It harvests cancer cells from a patients blood sample, isolating tumor cells based on size and deformity, for analysis. It takes about two hours for results.

Moores laboratory at Wilmot was the sole location nationally to test whether the technology produces the same results each time, a research concept known as reproducibility. He also was an investigator on several clinical trials sponsored by ANGLE, enrolling more than 500 local women during the past few years in breast and ovarian cancer trials.

Technology like this is a big deal because its designed to capture living cancer cells early on, before a tumor is found by conventional means such as a CT scan or a surgical biopsy, Moore said.

And if tumor cells are detected, Moore said, the technology also allows us to test for gene expression to discover if a patient could benefit from a treatment that would target those genes all from a simple blood draw."

Kyu Kwang Kim, Ph.D., research assistant professor of Obstetrics and Gynecology at URMC, and Negar Khazan, Ph.D., performed the work in the Moore lab. All of the data generated at Wilmot was part of the companys FDA submission, ANGLE said. Moore is continuing to work with teams at ANGLE, which is also funding studies using the Parsotix system to detect ovarian and endometrial cancer.

Investigation of liquid biopsies is exploding; in fact, another Wilmot team led by James McGrath, Ph.D., and Jonathan Flax, M.D., is developing a liquid biopsy test to detect cancer-specific cells for colorectal cancer, which disproportionately impacts Black individuals in the 27-county region from which Wilmot draws patients.

What Does Cancer Look Like?

For some types of cancer, such as ovarian, routine screening and early detection is not always possible.

Akshya Gupta, MD

This is why research led by Akshya Gupta, M.D., assistant professor of Imaging Sciences at URMC is important: He validated an accurate way to classify pelvic lesions that show up periodically in women who do not have a high risk of ovarian cancer. The study showed that based on ultrasound appearance, pelvic lesions can be effectively placed into two categories classic and non-classic with 93 percent sensitivity.

Classic is for fluid- or fat-filled cysts that carry a very low risk of being cancerous.

The incidence of ovarian cancer in the general population is very low and the vast majority of lesions that we see as radiologists have classic, benign features where the risk of cancer is exceptionally low, below 1%, Gupta said. Thats reassuring.

But what separates the classic lesions from the ones that need immediate attention?

Non-classic masses usually have a solid component or blood flow within the lesion that can be seen on Doppler ultrasound. Of the 970 lesions analyzed in Guptas study, the non-classic ones had a 32 percent frequency of malignancy in younger women and a 50 percent chance of being cancer in older women.

Gupta explained that algorithms have existed for years to assess pelvic lesions but they are often based on patients who have already been referred for surgery or to a gynecological oncologist. These women have a higher incidence of cancer compared to the general population.

Therefore, he said, the classic versus non-classic approach can help to stratify lesions when radiologists are called upon to triage women of average risk for ovarian cancer. Many of these cases come about when women go to their doctors with concerns about an ovarian cyst, minor abnormal bleeding, or if a small pelvic mass is discovered incidentally during an evaluation for a different health issue.

Read more here:

Concerned about Breast and Ovarian Cancer? Research Brings Progress - URMC

Boris Johnson lost the support of all his key backers in the final months before his resignation, with the Brexiters and rightwing culture warriors who cheered him to victory the first to melt away, followed by once loyal cabinet ministers. But one group will be lamenting the end of the Johnson era: green Tories have seen the prime minister as their best hope for years, and are concerned that his successor will not live up to his promises.

Johnsons premiership has brought more major environmental legislation and arguably greater progress on tackling the climate and nature crises than either of his Conservative predecessors in the past decade.

Three landmark acts of parliament the Agriculture Act, the Fisheries Act, and the Environment Act as well as a plan for reaching net zero emissions, an energy security strategy and the Cop26 UN climate summit in Glasgow last November, have made for an energetic two and a half years. Johnson has also overseen plans to phase out petrol and diesel cars, a boom in offshore wind, and a pledge to protect a third of the UKs land and seas.

Sam Hall, of the Conservative Environment Network, said green policies were always central to Johnson, not an add-on. Despite the political turbulence caused by Brexit and the pressures of responding to the pandemic, the prime minister has delivered an impressive amount of new green policy domestically and prioritised environmental issues in international fora, such as Cop26 and the G7.

Net zero in particular has been viewed as integral to the governments levelling up strategy, with a huge amount of new investment set to flow into the UKs industrial heartlands as a result of our net zero goal. In response to the Ukraine crisis, the prime minister has doubled down on renewables in order to bolster the UKs energy security and ease the cost of living, although he has not been able to unlock further support for energy efficiency from the Treasury.

Ben Goldsmith, a prominent green Tory supporter and brother to Zac, the Foreign Office minister elevated to the Lords by Johnson, said: I have not seen a prime minister before who has placed such importance on the climate and nature recovery. It has been greater than we have seen from any previous government.

Goldsmith emphasised Johnsons genuine interest in nature and animal welfare issues, shared by his wife Carrie Johnson. He has a sense of the sacred, said Goldsmith. Nature really matters to him. Im not sure many political leaders share that.

Even diehard green campaigners give Johnson credit. Dave Timms, head of political affairs at Friends of the Earth, said: As prime minister, Johnson increasingly made the climate crisis part of both his personal and the Conservative partys public narrative. His rhetoric at moments such as the UN climate negotiations, while idiosyncratic, did not shy from acknowledging the level of catastrophe the world was facing, nor the urgency of action needed.

But campaigners also said Johnsons green achievements were fragile, flawed and undermined by U-turns and omissions. Along the way there have also been victories for the Tory partys rightwing Net Zero Scrutiny Group, set up to obstruct climate policies. And alongside announcements such as a 10-point plan to build back better from the pandemic, there have been policy failures and gaps, as well as many measures road-building, airport expansion, new North Sea oil and gas licensing and a mooted new coalmine that run counter to Johnsons professed green ambitions.

It is a tragedy that he seemed incapable of turning [his rhetoric] into decisive and consistent domestic action across government to address this crisis, said Timms. Key departments were allowed to act as if the climate crisis were an optional extra or in the case of Rishi Sunaks Treasury, actively undermine efforts with tax breaks for short-haul flights, cuts to insulation programmes, and a road-building bonanza.

The windfall tax on oil and gas companies is another example: the way it is being implemented means it could, perversely, boost fossil fuel production as companies can largely escape the tax by investing in new oil and gas development in the North Sea.

On nature protection, too, rhetoric has outstripped reality, according to Richard Benwell, chief executive of the Wildlife and Countryside Link charity. Johnson has made some excellent promises But there remains a major gap between promise and practical action, he said.

Urgent investment was needed, on water quality and habitat restoration, and to improve the UKs farmed land, but these were all unfinished, unenforced and underfunded, said Benwell, and some proposals would weaken our most important nature conservation laws.

Those failures will be what counts, added Timms. The cost, in economic and social terms, of not acting [on the environment] will completely overshadow money spent now moving us towards a zero-carbon future. Measures like comprehensive home insulation programmes will save money on fuel bills, investing in green energy will free us from the tyranny of volatile fossil fuel prices. Hundreds of thousands of new and long-term jobs can be created, but the longer we leave action the more expensive and more damaging the final bill will be.

Johnsons inability to keep a grip on his party has opened up an even greater danger: the prospect that his successor could ditch his green slant to appease the Tory right. His scandals have already given space for some who were always unhappy with green policies to air their grievances.

The Net Zero Scrutiny Group of about 20 Tory MPs has suggested that net zero should be pushed back as it is too expensive, and that more investment in fossil fuels is needed to combat energy price rises. Hall called the Net Zero Scrutiny Group a noisy minority within the party, while the Conservative Environment Network counts more than 100 MPs as members. Their impact, however, means the would-be green prime minister leaves a confused legacy, and environmentally minded Tories must scramble to salvage what they can from the policy wreckage.

Their claims have little basis in fact: the UKs energy price crisis is down to the overreliance on gas fostered by the failure to invest in renewables and energy efficiency, and seeking further reliance on gas just stores up problems for the future. But the anti-green rhetoric gained traction in the rightwing press, and appears to be influencing Johnsons potential successors: Rishi Sunak and Liz Truss have been notably cool on green issues.

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Joshua Marks, of the BrightBlue thinktank, which advocates green policies from a Conservative standpoint, warned that Johnsons failures would mark the UK for years to come. Johnson envisaged himself as a green tsar whose lasting legacy is the decarbonisation and levelling up of Britain through a transition to a low-carbon economy. With distractions such as coronavirus, I suspect he wont be remembered as such, he said.

Read more here:

Green Tories fear lurch away from progress on climate after Johnson - The Guardian

All eyes are on James Wiseman as the third-year center gears up for Summer League action.

Golden State Summer League head coach Jama Mahlalelajoined 95.7 The Games Willard & Dibs to give the latest update on the 21-year-old, who didnt appear in the teams three California Classic games at Chase Center last week.

So, when can we expect to see Wiseman return to the floor? The Warriors open Summer League action on Friday at 5 p.m. PT against the New York Knicks before coming back on Sunday at 4:30 p.m. PT, which you can hear on 95.7 The Game.

I think hes not gonna play the first game of Summer League, we all know that, Mahlalela told Mark Willard and Larry Krueger, filling in for Dan Dibley. But he's trending well to play after that. I'm not sure if it'll be Game 2 or Game 3, but the guy's really put his head down and his body's doing really great. So well see. In the coming days hell definitely get out on the court. Were so excited for it.

Mahlalela also detailed what Wisemans workload is currently like, as he is about 15 months removed from a tear in his right meniscus.

The guys making amazing progress, Mahlalela said. Were doing scrimmages with some guys on our roster and some guys on our Summer League team. Hes been playing a day, resting a day, playing a day, resting a day. Hes doing really well.

The Warriors shared video of Wiseman sinking a 3-pointer in Thursday's scrimmage.

The Athletic's Marcus Thompson II tweeted out his observations from Thursday's scrimmage in Las Vegas, saying Wiseman had good touch but still needs to improve his conditioning.

Wiseman appeared in three G League games in March before being shut down for the season, wiping out his entire second NBA season. He seemed to hit a wall in his rehab in November of last year and underwent a cleanout procedure in December. Warriors president/general manager Bob Myers also reportedly flewto London with Wiseman in April so he could get a platelet-rich plasma injection to stimulate recovery in his knee.

In 39 games during his rocky rookie campaign, the No. 2 overall pick averaged 11.5 points and 5.8 rebounds per game while shooting 51.9 percent from the floor. The Warriors would love to add the 7-footers length and athleticism to their bench as a solid backup for Kevon Looney, who returned to the Warriors on a three-year deal last week.

Obviously, his size is the first, most impressive thing, Mahlalela said. We all know that and can sense that right away. But I think as he starts to scrimmage more, were starting to really learn some of the nuances of the game. His hands are really good, he can shoot the ball, which we all knew, but hes finding when to shoot the ball a bit better. And then obviously, the ability to protect the rim. Thats what will be the focus for us, as we start to be able to move more, well continue to coach him up and work on his rim protection and ability to protect the paint.

On Thursday, Mahlalela reportedly was promoted from player-development coach to a front-of-bench assistant coach role, so hes had a close on Wisemans growth behind the scenes.

Link:

James Wiseman 'making amazing progress' expected to play Vegas Summer League - 95.7 The Game

President Biden on Wednesday insisted that his administration has made incredible progress on the economy and said the blame for inflation rests squarely with Russian President Vladimir Putin, as he made a pitch to workers in a longtime bellwether state.

Mr. Biden, who faces strong political headwinds amid 40-year high inflation and skyrocketing gas prices heading into Novembers midterm elections, delivered the remarks on his sixth visit to Ohio since taking office in a bid to woo blue-collar union voters frustrated by the countrys economic woes.

We made incredible progress on the economy from where we were a year and a half ago, Mr. Biden told a room full of ironworkers at a union training center in Cleveland, arguing that the disruptions to world oil and food markets caused by Russias invasion of Ukraine were the primary culprit behind rising prices.

Weve got a long way to go because of inflation, he said. I call it the Putin tax increase.

The presidents trip was organized around the rollout of a program under the $1.9 trillion American Rescue Plan, which Mr. Biden signed into law in March of last year, designed to shore up multiemployer pensions which have faced significant cuts in recent years. Democrats have struggled to bank a major political payoff from the giant spending plan.

More than 200 multiemployer pension plans are on track to insolvency in the near future, according to White House figures. Without the Special Finance Assistance program, which allows pension plans to apply for federal assistance, up to 3 million workers who paid into their pensions would see their benefits cut in retirement, the administration warned.

SEE ALSO: Bidens woes on display as Ohio Democratic candidates beg off joint appearance

But the presidents visit to Ohio, which former President Donald Trump carried in both 2016 and 2020, was a clear bid by Democrats to get out in front on pocketbook issues and claw back voters.

Its pretty clear Democrats and the president have some problems with blue-collar voters, at least blue-collar White voters, said Democratic strategist Brad Bannon. The very fact that he has issues with blue-collar voters is a good reason to go there and talk about blue-collar issues like jobs and pensions.

But the president has significant ground to recover as Americans economic fears grow and as his poll numbers sink.

Critics have blasted the administrations domestic spending agenda, including the $1.9 trillion legislation that included the pension assistance program that Mr. Biden unveiled on Wednesday, as a key driver behind inflation.

Mr. Biden has scrambled to control skyrocketing gas prices by pressuring Congress and the states to temporarily suspend gas taxes. He has also accused oil companies of profiteering with outsized price hikes at the pump as Americans hit the road for the summer driving season.

Congress has yet to act on the presidents proposal on the gas tax, but after reaching record highs last month world gas prices are on the decline in recent days.

The White House has also touted what it says is a strong labor market the U.S. unemployment rate was just 3.6% in June and Ohios was only slightly higher at 3.9% as a sign that Mr. Bidens economic policies are having a positive effect.

But there seems little chance Democrats will be able to sidestep voter anger over inflation in upcoming elections, especially when it comes to lower-wage workers who are feeling the pinch.

If [inflation] continues to rise, as it has been, thats obviously a big problem for the president and Democrats, Mr. Bannon said. If its down significantly between now and Election Day, I think the other aspects of the presidents economic success will come more into play.

Mr. Biden on Wednesday almost pleaded with Ohio voters to stick with the Democrats, in a state where the party thinks it has a chance of winning the open seat held by retiring Republican Sen. Rob Portman.

He warned of what he said were Republican plans to cut social programs and raise taxes on the middle class, and blamed the GOP for standing in the way as Democrats fight to lower costs for the middle class.

Now Im fighting like hell to lower costs on things we talked about around your kitchen table, he said. Thats why elections have consequences. Thats why they matter.

Read more:

Biden touts 'incredible progress' on economy in bid to salvage Ohio's blue-collar vote - Washington Times

(Photo by Jamie Sabau/Getty Images)

The Baltimore Orioles are slowly but surely taking steps back towards respectability.

Since reaching the postseason in 2012, 2014, and 2016, the Orioles have not been the same and have fallen on hard times, finishing at the bottom of the American League East in every season since then, save for the pandemic-shortened 2020 season.

But last night, they picked up win No. 40, which is their fifth consecutive win.

Their 4-1 win over the slumping Los Angeles Angels put them to within four games of the .500 mark and netted them their first five-game winning streak since August of 2020.

StatMuse on Twitter posted about the Orioles recent accomplishment and how theyve made a little incremental progress.

The Orioles have won their 5th straight game tonight after defeating the Angels.

This is the first Orioles 5-game winning streak since August 12, 2020.@OriolesMuse_ pic.twitter.com/29nPMwlIdQ

StatMuse (@statmuse) July 8, 2022

Baltimore still sits at the bottom of the AL East division, 20.5 games back of the surging New York Yankees, but theyve come to within five games of the final AL Wild Card spot, which is currently held by the Toronto Blue Jays.

Slowly, but surely, the Orioles are making a little progress and coming closer to becoming a contender again.

Anytime you can win five games in a row, its a big step forward, especially for the Orioles, given that they had yet to do that since 2020.

Its been a while since the Orioles were close in the playoff race.

Even in 2020, when they had their most recent five-game win streak, they werent ever close in the postseason race.

But now, theyve inched ever so closer to a Wild Card spot.

Perhaps that will be enough for them to ultimately decide to go out and pick up some pieces at the trade deadline to either prepare for a stretch run or add some stars for 2023 and beyond.

Visit link:

Orioles Making Progress By Piecing Together Wins - The Cold Wire

Heart failure with preserved ejection fraction (HFpEF) can arise from a range of genetic and physiological triggers, but the common denominatorelevated left atrial (LA) pressurehas spawned a host of investigational interatrial shunt devices aimed at LA decompression. After nearly a decade of research, most single-arm studies have showed improvements in exercise capacity and quality of life, along with reductions in pulmonary capillary wedge pressure (PCWP) at rest or during exercise.

The first randomized, controlled trial in this space, however, showed no benefit to shunt implantation versus a sham procedure, begging the question: is hope still afloat for the theory that making a hole in the heart can help in HFpEF?

A flurry of recent studies imply that the field is forging on. The EuroPCR, European Society of Cardiology Heart Failure (ESC-HF), Society for Cardiovascular Angiography and Interventions (SCAI), and TVT meetings this spring all featured new study results, new technologies, or updated analyses from prior presentations and publications. Thats despite the fact that REDUCE LAP-HF II, the largest trial to date, testing the Corvia interatrial shunt in HFpEF, came up short. The trial was presented at THT 2022 in February and published simultaneously in the Lancet.

I think there's still a lot of excitement, the lead investigator for REDUCE LAP-HF II, Sanjiv Shah, MD (Northwestern University Feinberg School of Medicine, Chicago, IL), told TCTMD, citing examples of other, earlier-stage innovations and approaches that are moving forward. There's still a lot of interest and we're just going to have to see, he said.

While most of the studies to date have been small, single-arm series with surrogate endpoints, results have been more or less consistent in demonstrating that the procedure is safe, reliably reduces LA pressures, and improves exercise capacity, Shah noted. There remains a lot of industry investment in the field, as well, he said.

There's still a lot of interest and we're just going to have to see. Sanjiv Shah

The idea that an iatrogenic shunt could be helpful in this setting stems from the fact that elevated LA pressure tends to cause similar symptoms in HFpEF as it does in mitral stenosis, as Lars Lund, MD, PhD (Karolinska Institutet, Stockholm, Sweden), explained to TCTMD. More than a century ago, researchers noted that mitral stenosis progression tended to be delayed or attenuated in patients who also had a congenital atrial septal defect. That led to the theory that creating a hole in the septum of heart failure patients with elevated LA pressures might also alleviate their heart failure symptoms.

Daniel Burkhoff, MD, PhD (Cardiovascular Research foundation, New York, NY), who has also been involved in the REDUCE-LAP HF trials with the Corvia device, estimates that there are at least seven companies working in this spacefour developing implantable devices (Corvia, V-Wave, Edwards Lifesciences, and Occlutech) and three working on shunt-creation approaches that leave no device behind (Alleviant, NoYa, and InterShunt).

The Edwards and Occlutech devices are both in early feasibility studies, ALt FLOW US (55 patients) and PRELIEVE (106 patients), both with estimated completion dates in 2022.

Ive found it encouraging that most of the projects I'm aware of are continuing, Burkhoff said. There are none that I've heard are stopping. Enrollment continues in other studies aside from the Corvia study. The farthest along, he noted, is RELIEVE-HF, testing V-Waves Ventura interatrial shuntdevice across the spectrum of ejection fraction. The study aims to enroll 500 patients at 120 sites internationally, with a plan to scale up to 1,000 patients based on interim analysis findings.

It's almost as though the Corvia study had minimal impact on the momentum, at least for the companies, to continue, Burkhoff said.

Corvias Setback

As reported by TCTMD, REDUCE LAP-HF II, conducted at 89 sites internationally, randomized 626 patients (out of 1,072screened) to an atrial shunt device or a sham procedure. All patients had to have an ejection fraction of 40% or higher and exercise PCWP 25 mm Hg while exceeding right atrial pressure by at least 5 mm Hg. Patients with right ventricular enlargement or dysfunction were excluded.

At 12 months, there was no significant difference in the cumulative rate of cardiovascular death or stroke between groups, although it was numerically lower in the sham-treated patients. By 24 months, however, there was no difference in cumulative rates of heart failure events or a composite safety endpoint, but patients in the shunt group had experienced more cardiac events than those in the sham: 4% versus 1% (P= 0.025).

Delving deeper into this signal, investigators found that patients who did not have evidence of latent pulmonary vascular disease (PVD) based on invasive exercise hemodynamics appeared to benefit from shunt placement, whereas those with latent PVD fared worse. Patients with prior pacemakers also appeared to do poorly with shunt placement.

The pacemaker is almost like a sign that the right heart is sick and even if it didn't show up on the echo, even if patients met the inclusion criteria, that right ventricle is more vulnerable and they do worse, at least with the Corvia device, Shah explained.

As a result, he added, patients with pacemakers will be excluded in the next Corvia trial.

Gaining More Insights

Whether and how much the presence of PVD can or should be used to define the patients best suited to this procedure is unclear. An unblinded snapshot of patients participating in the nonrandomized roll-in phase of the RELIEVE-HF trial of the V-Wave device, also presented at THT 2022 back in February, suggest that shunt sizepotentially in relation to PVDmay also be key. RELIEVE-HF investigators at THT were quick to point out that the shunt created with the V-Wave is smaller than that of Corvia (5 mm vs 8 mm), which might help explain their promising, albeit unblinded, early results.

There are many patients who subjectively suffer a lot from their poor quality of life and functional capacity. Lars Lund

That theory was further explored in a presentation by Julio Nuez Villota, MD, PhD (University ofValencia, Spain), at the ESC-HF meeting in May. In an analysis derived from echocardiographic data, investigators estimated that the 5-mm shunt produced by the V-Wave creates just the right amount of shunt flow, said Nuez Villota in Madrid, decompressing the left atrium without adverse effects on the right heart or pulmonary circulation. By contrast, he explained, an 8-mm shunt leads to double the amount of shunt flow at any gradient, with deleterious effects on right ventricle function.

Patients treated with the V-Wave shunt, he noted, also showed significant gains in left ventricular ejection fraction at 1 year, as well as improvements in RV systolic function and left and right ventricle dimensions.

To our delight, we found multiple indicators that the right ventricle was actually getting better, Nuez Villota is quoted in a V-Wave press release summarizing the ESC-HF presentation. This may be clinically important considering the recent negative REDUCE-LAP-HF II trial that used a different and larger 8-mm interatrial shunt that has about twice the flow as the 5-mm V-Wave Ventura Shunt.

RELIEVE-HF, said Nuez Villota, is expected to finish recruitment this fall.

The Ideal Patient

Whats clear is that the accumulating data are carving away at the patient population best suited to this type of device therapy.

You really cannot have right-sided heart failure at all, if you're going to benefit from this intervention,because the increased flow of blood to the right is going to compromise your right-sided function further, Lund told TCTMD. Add to this the emergence of latent pulmonary vascular disease and pulmonary resistance as a contraindication, not to mention the dearth of centers capable of performing the invasive tests required to definitively diagnose these conditions, and the pool of patients shrinks further.

Thats a further subgroup of a subgroup of a subgroup, so to speak, Lund said. Going forward, companies need to pick patients who have a normal or good right-sided function at rest. That was already known, and that still applies. Also, patients who do not have resistance in the lungs at rest: that was known, and that still applies. But thirdly, they need to pick patients who also do not get increased resistance during exercise and that was previously not known, but that is known now as a result of [REDUCE-LAP HF II].

Investigators moving into next stage testing will likely consider all of these factors in refining their upcoming or ongoing clinical trials, Lund added.

Worth noting, said Burkhoff, is that V-Wave is not only focused exclusively on HFpEF patients, but has not embraced exercise testing as part of its clinical trial/patient selection process.

I suspect if they have a negative trial like Corvias, they will be able to find another subgroup that doesn't rely on that, that's just the way subgroup analyses work, he said. They'll find some resting or other noninvasive thing thatalso correlates with outcome.

And whether that, in turn, proves to be a good or comparable way to hone patient selection will again need confirmation in further studies.

Shah pointed out that even if the patient population shrinks, it is by no means small. In REDUCE-LAP HF II, even after excluding patients with a pulmonary vascular resistance greater than 1.74 Wood units at peak exercise and/or a pacemaker, that still leaves more than 50% of patients eligible.

People might say, well thats just a sliver of the population, but it turns out it's about 2 million people in the US that fit the inclusion criteria for the next trial. So this still could have a major benefit for a lot of patients, Shah argued. And who's to say, it could be that in patients with an exercise pulmonary vascular resistance above 1.74, we might be able to treat them with pulmonary vasodilators like sildenafil to get that number down and then they'll be candidates for the device, potentially.

Whether that population is sizeable enough to be attractive to the companies trying to bring these shunts to market is another thing entirely, Lund noted.

If indeed a future trial showed that a subgroup of a subgroup of a subgroup benefits from this treatment, the implementation is going is still going to be limited, Lund said. But it's such a large population and there are many patients who subjectively suffer a lot from their poor quality of life and functional capacity. . . . I don't think any investigator or sponsor or company anticipates that this is going to be a large [market], but I think many do consider the possibility that it'll be a small and specific item that helps a not insignificant proportion of patients.

The question of ideal shunt size, device, or technique also awaits more data. At ESC-HF in May, Lund presented early results with Alleviant Medicals no-implant interatrial shunt technology in the ALLEVIATE-HF 1 and 2 first-in-human, nonrandomized trials. The same data were presented by Peter Fail, MD (Cardiovascular Institute of the South, Houma, LA), at TVT 2022 in June.

As both Lund and Fail showed in their presentations, patients treated with the Alleviant no-shunt technique had statistically significant improvement in peak exercise PCWP and NT-proBNP and sustained improvement in symptoms and NYHA functional class. The system excises tissue via mechanical compression and a short pulse of radiofrequency energy to create a roughly 7-mm shunt with smooth, rounded edges, stable patency, and uniform endothelialization.

Investigators are moving forward with a pivotal study, Lund said.

Next Horizons

For now, all eyes will be watching for the randomized V-Wave results, anticipated for late 2022 or early 2023. If positive, the narrow inclusion criteria implied by the REDUCE-LAP HF II findings will be revisited, particularly given the inclusion of HFrEF patients in the study.

According to Shah, the truly HFpEF patients in REDUCE-LAP HF IIthose with ejection fractions greater than 50%appear to have gleaned the most benefit from a shunt.

I think it will be really interesting to see, throughout the full spectrum of EF, does it work better in HFpEF or HFrEF or somewhere in the middle? That still needs to be determined, Shah said, but I do think that it's going to be tough to do studies in HFrEF and even moderately reduced EF, because there are so many medical options already.

Its also not clear when in the disease process an interatrial shunt might work best.

Normally later-stage patients, once they start progressing, the right heart gets sicker, the pulmonary vascular resistance goes up, so you can't wait too long. In that sense, earlier may be better, Shah speculated. On the other hand, typically we reserve devices for later on, when somebody has failed medical therapy. So I think there's going to be a sweet spot for devices like this, where patients are not too sick in right heart failure, but you've tried SGLT2 inhibitors, youve tried mineral corticoid receptor antagonists, and theyre still struggling.

It's almost as though the Corvia study had minimal impact on the momentum, at least for the companies, to continue. Daniel Burkhoff

At that point, he continued, if you do a right heart catheterization and their pulmonary capillary wedge pressure at rest is normal, but it goes way up with exercise, medically there's nothing we have for treatment. . . . Thats the kind of patient that I think we really struggle with, that could potentially benefit from a shunt device.

For the large majority of heart failure specialists more comfortable with drug therapies than with interventional devices, interatrial shunts have a long road to travel. Lunds prediction is that with the right, highly selected trial population, interatrial shunts will likely prove to enhance quality of life and functional capacity but not have an impact on heart failure hospitalizations or death. Regulators, he noted, are increasingly open to accepting patient-centered endpoints in trials, so this may not be a barrier.

Reimbursement may be a separate hurdle, particularly in places like the United States, he predicted. Yet this may ultimately help ensure that only patients who meet the strict conditions established by trials end up being the ones who get the devices.

The biggest stumbling block, he said, may be among the heart failure doctors themselves.

There needs to be awareness and willingness and capabilities, broadly in the community, and I think that that will also exist but be very limited, said Lund. My prediction is that this approach will become clinically available, approved, and reimbursed, but will be utilized poorly or little and that will be a concern for the companies.

Burkhoff said REDUCE-LAP II was undoubtedly a setback, and there were certainly some in the heart failure community at large that did not think this would work, from the beginning, and obviously this reinforces their thinking.

But for now, physicians eager for new therapies, particularly for HFpEF patients are, appropriately, awaiting more data. The heart failure community in general is very conservative, Burkhoff said. They are willing to participate in clinical trials, [but] they are reticent to endorse or express premature enthusiasm, for any therapy.

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A Hole in the Heart for HFpEF? Setbacks, Progress for Interatrial Shunts - TCTMD

Have you dined in a downtown SLO parklet? Maybe you sat on Monterey Street and enjoyed some Italian fare from Giuseppe's Cucina Rustica, whose parklet helped turn Monterey into a one-way street between Chorro and Morro. Or maybe you grabbed a slice at Woodstock's Pizza and ate along Higuera. Or maybe you enjoyed a farm-to-table nosh from Big Sky Caf on the side of Broad. Or maybe you refuse to go to downtown SLO because parking sucks and San Luis is elitist and you remember the good old days. Wah!

The city's temporary parklet program grew out of the COVID-19 pandemic as an attempt to save struggling restaurants during state-mandated lockdown orders. Depending on how you feel about al fresco dining, the parklets were either ingenious or a debacle that made the city's already challenging parking situation even worse.

Can we at least all agree that cocktails-to-go was brilliant? Of course we can't, because we can't agree on anything.

So who wants a permanent parklet program? Not letter writer Rene Scarnegi, who implored the SLO City Council: "This is something that can't be approved! The parklet program served our businesses downtown when they were needed during the pandemic. Nowalmost post-pandemicthey are not needed and we need to get our streets and parking spaces back ... parklets are eyesores!"

Well, bad news, Rene, because parklets are officially here to stay. The council just voted to make the program permanent ... for a price. A steep one at that. How does $8,710 per parking space per year sound?

Woodstock's is going to need to sell a lot of slices if it hopes to keep its three-plus parking space dining parklet open, and co-owner Laura Ambrose couldn't quite get her head around the proposed fees in her letter to the City Council.

"With our current set-up, we will be looking at an annual cost of nearly $28,500 starting next year. A rate of $4.54/square foot for a spot in the street is considerably higher than what we're paying for our fully built-out restaurant building!" she said.

Lucky for her, City Council knocked that fee back to $6,760! Still, a lot. Not only are the new fees exorbitant, but the parklet program now comes with new requirements such as Americans with Disabilities Act compliance and dedicated bicycle parking. She went on to break down the city's fees such as manual street sweeping, which would be $11,700 for Woodstock's three spaces.

"We frequently sweep our outside dining area and will be happy to maintain this without city staff coming in with brooms," she wrote. "We find it hard to believe that sweeping around our parklet alone is costing the city $225/week."

Then Ambrose took umbrage with the city's estimated parking revenue loss of $12,000 for Woodstock's parklet: "This assumes that people will not come downtown and park any longer," she posited. "No, they will just park in other parking spotseither on the street or in one of the city-owned parking structures. So no revenue loss."

She may have a point here. According to the city, there are a little more than 1,000 downtown street parking spaces, and only 50 are currently used by parkletsless than 2 percent of total.

And then there's the charge for tree trimming around parklets$930 a year for Woodstock's: "I realize this is an estimate," Ambrose continued, "but we don't actually have any trees around our parklet."

Sad. Some trees would be nice!

The city has a new parking structure it's trying to finance, which is why about six weeks ago it proposed doubling parking meter fees downtown. According to councilmember Andy Pease, that change is about a year away as the city looks for other options. As far as Big Sky Caf owner Greg Holt is concerned, he's starting to feel he is the other option.

"Perhaps, finding another method of balancing the budget without the individual business covering the entire lost city parking income might be a good thing," Holt wrote.

Perhaps, indeed.

Here's a philosophical thought: If nearly 4,000 oak trees fall in Nipomo's Dana Reserve and everyone is around to hear it, how loud will the protest be? Well, hang on to your hearing aids, because we're about to find out.

Local development firm NKT Commercial wants to build 1,289 single- and multi-family units on Caada Ranch, a 288-acre site off Highway 101, but that means cutting down 76 percent of the parcel's oak forest. According to the draft environmental impact report (EIR): "Hey, no biggie!"

Just kidding! It will be horrible! The woodland "provides important native habitat for plants and wildlife" and "contributes significantly to ... the region's overall biological diversity," supporting eight special-status plants and four special-status nesting birds.

Go away, special-status plants and birds! People need to live here!

Let's estimate 3,000 new people will live in these 1,289 units. Can Nipomo absorb these new humans? The EIR says nope, not really: The project is not "specifically projected or planned for in local and regional county planning documents" and would "induce substantial unplanned population growth in the Nipomo area."

In the immortal words of Joni Mitchell, it looks like we're about to pave paradise and put up a parking lot. Ah, progress!

The Shredder is tone deaf. Yell by emailing shredder@newtimesslo.com.

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The price of progress? - New Times SLO

A new research conducted by the Pew Research Center has found that most employees who quit their work in 2021, did so due to low pay, lack of opportunities for advancement and because they felt disrespected at work.

2021 saw one of the highest quit rate among employees, America reporting an almost 20 year high. Widespread job losses in the early months of the pandemic gave way to tight labor markets in 2021, driven in part by whats come to be known as the Great Resignation.

The employees who quit their previous organisation have also said that they are now employed elsewhere and are more likely than not to say their current job has better pay, more opportunities for advancement and more work-life balance and flexibility, according tot he survey.

The study conducted by Pew Research Centre found majorities of workers who quit a job in 2021 say low pay (63%), no opportunities for advancement (63%) and feeling disrespected at work (57%) were reasons why they quit, according to the Feb. 7-13 survey.

the research also saw that roughly half say child care issues were a reason they quit a job (48% among those with a child younger than 18 in the household). A similar share point to a lack of flexibility to choose when they put in their hours (45%) or not having good benefits such as health insurance and paid time off (43%). Roughly a quarter say each of these was a major reason.

Further, the Per Research Centre survey found that adults younger than 30 are far more likely than older adults to have voluntarily left their job last year: 37% of young adults say they did this, compared with 17% of those ages 30 to 49, 9% of those ages 50 to 64 and 5% of those ages 65 and older.

Meanwhile, the Great Resignation is most likely to continue in 2022 in India with a whopping 86 per cent of employees planning to resign in the next six months, recruitment agency Michael Page stated in a report.

Almost 60% Indian employees in India are willing to accept a lower salary or forgo a pay rise and/or a promotion to focus on better work-life balance, overall well-being and happiness, found the Michael Page report.

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Low pay, disrespect, no progress are top reasons why workers quit their jobs in 2021, finds survey | Mint - Mint

GLACIER NATIONAL PARKThe full opening of Glaciers Going-to-the-Sun Road has been pushed back due to a cold and wet spring, but snowplows continue to make steady progress.

It took us two weeks to get through a spot that normally only takes a week at the most, said Glacier National Park Road Crew Lead Christian Tranel.

Tranel said heavy spring snow and avalanches caused his team to backtrack on snowplowing the road at least four times this spring due to dangerous conditions.

Sean Wells/MTN News

Typically, we would be open right now, even with how the snow looks right now, its just nature didnt cooperate very well with us, added Tranel.

USGS Physical Scientist Zachary Millers main job is forecasting avalanche conditions on Going-to-the-Sun Road.

"Its not a bad front office view, added Miller who noted that 50 avalanches have hit the road this spring.

Sean Wells/MTN News

What was different about this year compared to the last couple years is just that we saw that season in our main bulk of our avalanches come through, and the timing of them pushed back by two weeks to a month, said Miller.

Tranel said his main concern is the safety of his dozen or so snowplow drivers.

It can definitely wear on your mind after a while because thats the first thing you are always thinking of is all the what-ifs, what could happen, said Tranel.

Sean Wells/MTN News

Tranel has been working on Going-to-the-Sun Road for the past 11 years, an adrenaline rush like no other.

You have to have a healthy fear, you dont want to be so confident that youre not aware of what could happen, added Tranel.

Going-to-the-Sun Road through Logan Pass will open no sooner than July 13.

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Snowplow crews making progress on Going-to-the-Sun Road - KPAX News

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The Jaguars have wrapped up organized team activities and are set, ready to head into the mandatory minicamp portion of the offseason just before a five-six-week hiatus in preparation for training camp.

One player that has been in the crosshairs of plenty of media and fan observers is second-year running back Travis Etienne who spent his rookie season on the teams reserve/injured list due to a Lisfranc injury suffered during the teams preseason last year.

Since the media has been present at OTAs this year, plenty of clips and musings have come out about his speed and recovery from his devastating mid-foot injury. On the first day of OTAs, Etienne was given the vote of approval from head coach Doug Pederson, officially clearing him for full participation in on-field activities.

That part of the process was big; there was question regarding whether or not Etienne would make it back by training camp, let along being able to be a full go less than a year since he originally underwent surgery. Since his return to full participation, there hasnt appeared to be a drop-off in his ability. In fact, it appears according to many observers Etienne might have an opportunity to get back to his original self.

Thats huge, and Pederson echoed those same sentiments during the last media availability, just prior to the teams seventh OTA session on Monday, stating that hes progression really well.

Gosh, its just exciting to get him out here and get him on the grass this whole offseason and really work with him, Pederson said. Hes doing a great job handling a lot of information were throwing at the guys and putting him in different spots. [Were] just seeing what he can do right now.

Last year, former Jaguars head coach Urban Meyer drew some criticism amongst many observers and fans for putting Etienne at receiver, taking away his time from his best position as a running back. Well, that much hasnt change (though, perhaps the narrative surrounding it has). Etienne has taken snaps as a receiver, and moving him around the field is something the Jaguars hope they can continue throughout camp and into the season. It is fun. This is the time to do that stuff, to really experiment on both sides of the ball and just kind of see what the guys can do, and hes one of those guys, Pederson stated when asked about Etiennes ability to play at multiple spots on the field.

Part of the thought process with moving Etienne around is the ability to create mismatches for the opposing defense. Being able to have a couple of different players run around at different spots creates some confusion and allows for the offense to succeed. A player of Etiennes caliber, given his size, speed and agility, makes sense to utilize in that capacity.

For Jaguars quarterback Trevor Lawrence, getting Etienne back is significant. The two have had plenty of success in the past, playing together for three years at Clemson. Now, Lawrence might finally have the opportunity to repeat the success they had, just in the NFL.

It feels good, Lawrence said of getting Etienne back lining up with him Obviously last year, [we] didnt get to do much of that besides the first two preseason games, so its really nice having him back there. Just like Ive said about some other guys, he just adds another element to our offense.

Lawrence echoed the sentiments shared by Pederson; having different types of players giving opposing defenses a different look on a down-by-down basis allows the offense to take advantage of mismatches and confusion. Though its early, theres some progress and Etienne returning to what he once was is something important to keep an eye on.

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Travis Etiennes recovery and progress is encouraging - Big Cat Country