FIM Hard Enduro heads to Italy for Red Bull Abestone – TMXnews.co.uk

Pizza, pasta, and Hard Enduro! Its time for round four of the FIM Hard Enduro World Championship and Italys Red Bull Abestone.

Husqvarna Factory Racings Billy Bolt holds the lead in this years championship chase as we head to the halfway point in the season.

Gearing up for its second edition, Red Bull Abestone has already become a firm favourite for Hard Enduro fans thanks to its incredible landscape, tough riding, and awesome hospitality. Nestled high up in the Tuscany mountains, its a rare treat to ride these trails on dirt bikes. From deep on the forest floor to the ear-popping mountain peaks of almost 2,000 metres, Red Bull Abestone has Hard Enduro covered from all angles.

After being successfully introduced onto the Hard Enduro calendar by experienced racer Michele Bosi, the event has grown again in stature for 2022. Taking onboard rider feedback, the event will be staged across three days, offering a strong balance of riding to suit all abilities and tastes.

Friday offers the chance for competitors to stretch their legs on the Hard Enduro training loop in the mountains. Saturday will signal the start of the racing with the JUST1 qualification. An enjoyable 15-kilometre-long course will be ridden twice in the morning (Q1) and twice in the afternoon (Q2), with the combination of the fastest lap time from Q1 and Q2 counting towards Sundays racing.

The top 30 riders will advance to the LIQUI MOLY grand final on Sunday afternoon, while those outside the top 30 race the two-hour MITAS final on Sunday morning. As an added bonus, the top 16 from the JUST1 qualification will get the chance to race in the Straight Rhythm shootout on Saturday evening.

Getting down to the business end of the weekend, all eyes will turn to the LIQUI MOLY FINAL to determine the round four winner at Red Bull Abestone. Creating a spectacular backdrop, this years start line will be at 1,953 metres above sea level at the Abetone gondola. Riders will then face two laps of a track thats 31 kilometres long. With multiple signature sections to negotiate, it is set to prove quite the workout.

At the head of the standings, the points race is incredibly close as we enter the halfway point in this years championship fight. Husqvarna Factory Racings Billy Bolt holds the upper hand over his rivals with a two point lead over Sherco Factory Racings Mario Roman, with Red Bull KTM Factory Racings Manuel Lettenbichler just a further three points behind in third.

With numerous injuries to contend with so far this season, Billy has yet to show his true form despite leading. Hungry to pocket a win, hell be aiming to repeat his Red Bull Abestone victory from 2021. Roman is already a race winner in 2022 thanks to his victory at Israels Minus 400. He was a deserving runner-up last time out at Red Bull Erzbergrodeo and will look for more glory in Italy.

Despite missing the season opener in Israel due to injury, Lettenbichler has returned to the championship swinging. Victory at both Xross Hard Enduro and Red Bull Erzbergrodeo puts him as a danger man to both Roman and Bolt. Chasing his third win on the bounce at Red Bull Abestone could also earn him the championship lead too if everything goes his way.

In the Junior class its Rigo Racings Matt Green whos proven to be the rider to beat so far. The young South African has won both Junior rounds at Xross Hard Enduro and Red Bull Erzbergrodeo, while also fighting his way into the top 10 in the overall standings. Mitchell Brightmore (Rieju) and AG Racing Team 89s Suff Sella (KTM) are second and third respectively in points and will try to close Green down in Italy.

Round four of the FIM Hard Enduro World Championship takes place at Italys Red Bull Abestone on July 8-10.

1. Billy Bolt (Husqvarna) 45pts; 2. Mario Roman (Sherco) 43pts; 3. Manuel Lettenbichler (KTM) 40pts; 4. Alfredo Gomez (GASGAS) 34pts; 5. Wade Young (Sherco) 32pts; 6. Graham Jarvis (Husqvarna) 30pts; 7. Michael Walkner (GASGAS) 29pts; 8. Teodor Kabakchiev (KTM) 27pts; 9. David Cyprian (KTM) 24pts; 10. Dominik Olszowy (GASGAS) 21pts

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FIM Hard Enduro heads to Italy for Red Bull Abestone - TMXnews.co.uk

Amy Jackson and Beau Ed Westwick Make Heads Turn as They Walk Their First Red Carpet Together – News18

Ed Westwick, who is known for playing the character of Chuck Bass in Gossip Girl, and British actress Amy Jackson, made their relationship Instagram official earlier last month. They were seen at the 2022 National Film Awards in London recently. This was their first public appearance as a couple as well as the first time they walked the red carpet together. Looks like Chuck Bass has finally found his Blair Waldorf in real life, too.

While Ed looked dapper in a classic black tuxedo, Amy stole the show in a black dress with lace detailing. Amy and Ed reportedly started dating in December of 2021. Sources have it that the duo first met at the Red Sea Festival in Saudi Arabia.

All the rumours were confirmed after Amy posted a cozy picture of the two on Instagram.

Very recently the two were also spotted enjoying at the Wimbledon. Instagram updates shared by Ed Westwick on his birthday also suggest that Amy has been warming up to his family.

Ed had shared a photo of his grand mother and Amy from his 35th birthday party last month.

Amy, who is known in India for her roles in films like I and Singh is Bling, was previously engaged to George Panayiotou, a businessman based in London.

The pair had with great joy welcomed their beautiful son Andreas to the world in 2019. But something seemed to be off as Amy started deleting Georges pictures from her Instagram account. Later, the split between the two was confirmed.

On the other hand, Ed Westwick, who featured in movies like J.Edgar , Bone in the Throat after the end of Gossip Girl, the last being Me You Madness, has dated celebs in Hollywood. The most scandalous, however, remains his infamous so-called encounter with Drew Barrymore. Drew Barrymore and Ed Westwick were spotted and snapped making out at a Kings of Leon concert in Manhattan in September 2008.

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Amy Jackson and Beau Ed Westwick Make Heads Turn as They Walk Their First Red Carpet Together - News18

Using enough mulch is more important than what type you use: Dan Gill explains – NOLA.com

Garden columnist Dan Gill answers readers' questions each week. To send a question, email Gill at gnogardening@agcenter.lsu.edu.

I need to add mulch to my landscaping. I have used crushed pine straw in the past but find it pricey. I like the look, but budgetwise, I need a cheaper mulch. Also, is it necessary to remove the old mulch before adding the new? Ive been told that is the proper way to do it. Ruth Finley

Feel free to use a less expensive option. It is more important that you apply the mulch 2 to 3 inches thick than what type you use.

Do not remove the old mulch before spreading the new mulch. Spread the fresh mulch right over the old decaying mulch so that together the old mulch and new mulch form a layer 2 to 3 inches thick.

The layer of decomposing mulch is beneficial to the soil and the plants growing in the bed. Also, it saves you money because you don't have to add as much new mulch.

I was out of town for a week and returned to see a lot of brown stems where flowers had been on my cannas. I see no evidence that more flowers will open on the stalks with brown flowers. Should I cut the stalk off, and if so, how much? Wilma Stark

In gardening, we remove unattractive, faded flowers from our blooming plants, a process called deadheading. Yes, you may deadhead the cannas. It will make the planting look much neater and attractive.

You may do this two ways. Cut off the old flower stalk with faded flowers and seed pods back just to the first leaf.

But know that every shoot that a canna grows up from the ground blooms only once. New shoots that grow up over the summer will continue the floral display, but shoots that have already bloomed will not bloom again.

So, you also have the option of cutting a shoot that has already bloomed back all the way to the ground, removing it completely. This can be done to shoots that begin to look tired and unattractive or to thin out the growth to make room for new shoots.

Recently, I fertilized my outdoor potted plants with Miracle-Gro brand fertilizer. Several hours later, it rained hard but briefly. I was wondering if the rain likely washed the nutrients out of the soil. Judi

Im sure the rain did leach out some of the fertilizer. But the last time you watered the plants did, too. Minerals provided by soluble fertilizers are leached out of the soil and lost every time you water your container plants (or they get rained on). This is unavoidable.

Soluble fertilizers provide mineral nutrients in solution, and that makes them immediately available to be absorbed by the roots of plants. Thats a good thing. But because they are water soluble, it also means that they leach easily from the soil. That is why you need to reapply a soluble fertilizer every two weeks.

To avoid the need to fertilize containers so often, you can choose to use a slow release or controlled release fertilizer such as Osmocote or other brands. These fertilizers slowly release mineral nutrients over a long period of time. You need to apply them to containers only once at the beginning of the growing season.

Our large live oak was struck by lightning. Both sides of the trunk had bark damage. I don't know if there is anything I need to do for the tree. Phil and Sandra Van

Im so sorry to hear your old oak was struck by lightning. There is not much that can be done to help a tree that has been struck. Sometimes a struck tree will die in the months after the strike, but often they survive.

Remove (cut away) any loose bark, being careful not to pull off any bark still attached. If it survives the strike, fertilize the tree or have it professionally fertilized in February.

Ajuga makes a delightful ground cover, but it may be attacked by Southern blight.

AJUGA BLIGHT:Southern blight will attack plantings of ajuga this time of year, especially if the weather is rainy. Individual plants or whole areas of a planting will suddenly wilt and die. This disease is fairly common, and that makes the extensive use of this otherwise delightful ground cover questionable here.

HEAT STRESS: Some bedding plants may look a little stressed now. Blame the heat, both day and night. Many bedding plants (especially the tender perennials we grow as annuals) can be cut back in August. They will revive as the weather cools and provide color until November or longer.

PROTECT THE DECK: Container plants should not be placed directly onto wooden decks. The moisture underneath can damage the wood (saucers do the same thing). Boost pots off the surface an inch or two with pieces of brick or special pot supports (sometimes called pot feet) available at some nurseries and garden centers and online.

WATCH THE AZALEAS: Keep an eye out for azalea caterpillars, which are showing up on the north shore. These black and white caterpillars with red heads can virtually strip azalea bushes.

North shore gardeners should monitor their azaleas for damage and the presence of azalea caterpillars regularly. Treat with BT (Dipel, Thuricide) or spinosad these two insecticides are the least toxic choices or one of the pyrethroids, such as permethrin or bifenthrin, for quicker knock down.

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Using enough mulch is more important than what type you use: Dan Gill explains - NOLA.com

Selena Gomez Turns Heads At The Only Murders Premiere In A High-Slit Silver DressShes On Fire! – SheFinds

Selena Gomez just absolutely stunned in a sparkling silver dress with an epic high-slit while gracing the Only Murders In The Buildingred carpet premiere. The Lose You To Love Me hitmaker, 29, showed off her incredible figure at the Los Angeles event last week in a one-sleeve, glistening item from Michael Kors. The curve-hugging frock featured an waist-revealing side cut-out and high slit that flaunted her toned legs.

The Wizards of Waverly Place alum dazzled up her shimmering ensemble even more with matching silver sandal heels by Jimmy Choo and white gold diamond hoop earrings from Effy Jewelry. To complete her look, Gomez tied her long black tresses into a glamorous high ponytail, styled into elegant waves. Her gorgeous makeup consisted of a shiny silver eyeshadow, voluminous lashes, a glossy nude lip, and rosy blush along her cheekbones.

On the red carpet, Gomez spoke to reporters about the second season of her hit Hulu show, Only Murders In The Building, her character Mabel, and also shared her disgust at the Supreme Court overturning of Roe vs. Wade and urged viewers watching the premiere to head to her Instagram account for reproductive rights resources. Its about voting, Gomez said at the event. Its about getting men men needing to stand up and also speak against this issue.

She added, Its also the amount of women that are hurting. Im just not happy and I hope that we can do everything in our power to do something to change that.Later that evening, Gomez joined her co-stars Martin Short, and Steve Martin, for photos and continued to draw eyes to her stunning ensemble.

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Selena Gomez Turns Heads At The Only Murders Premiere In A High-Slit Silver DressShes On Fire! - SheFinds

Comey and McCabe Audits: How Likely That They Were a Coincidence? – The New York Times

The New York Times has reported that the Internal Revenue Service gave one of its most rigorous types of audits to James B. Comey, the former F.B.I. director, and to Andrew G. McCabe, his former deputy.

This has prompted a lot of perfectly reasonable questions, most of them variants of: What are the odds? As the article noted, the chances that two high-ranking political enemies of President Donald J. Trump were audited by pure coincidence are minuscule.

But minuscule is not zero.

If we wanted to believe this was a coincidence, how improbable would we say it was? Here, we try to estimate that probability as seriously as we can.

First, the facts: Both men were chosen for audits under the National Research Program (N.R.P.), a tiny subset of all the audits the I.R.S. performs each year. These audits scrutinize a sample of returns to gather data on tax compliance.

According to the I.R.S., there were about 5,000 such audits in 2017, 4,000 in 2018, and 8,000 in 2019 chosen from about 154 million individual tax returns each year. Mr. Comeys audit was for his 2017 tax return; Mr. McCabes was for his 2019 return.

Many aspects of the N.R.P. complicate our calculations, including the sampling methodology of I.R.S. auditors and the different years of the audits themselves. We will return to these issues later. For now, well assume all taxpayers have an equal chance of being audited and that both men were audited in 2017.

If this problem were to appear in a textbook about probability, it might read like this:

If there are 154 million marbles (the approximate number of tax returns filed each year) in a giant urn, and some small number of them are red (those representing Mr. Comey and Mr. McCabe among them), what are the chances that you will draw two or more red marbles if you randomly draw a few thousand from the urn (the number of audits in that year)?

It may sound complicated, but its a relatively well-studied problem, something many math or stats majors would encounter in their college coursework. People have already derived equations to estimate these probabilities, with names like the hypergeometric distribution, which has applications like election auditing and card counting.

We can simply enter our estimates for the number of total marbles, the number of red marbles and the number of draws, and well get a probability. If we believe there are just two red marbles that is, if we limit the exercise to only Mr. McCabe and Mr. Comey this equation yields a probability of roughly one in 950 million.

Those are considerably steeper odds than your chances of winning the Powerball. Its also an almost meaningless result. At best, its the right answer to the wrong question.

To understand why requires acknowledging an absurdity inherent in our exercise: To best estimate the likelihood of an improbable event, we must set aside the fact that we know that it already happened. (The probability that it happened is 100 percent.)

Jordan Ellenberg, a professor at the University of Wisconsin who has written books about math and reasoning, described it this way: In some counterfactual universe, what is the probability that this thing, which has already happened in our universe, happens?

It might seem odd, but the same issues come up even in probabilistic exercises as basic as flipping a coin.

If you flipped a coin 20 times, your specific sequence of heads and tails is extraordinarily rare, about one in a million, but it did happen. And some sequence of flips will always happen. Its a surprising coincidence only if thats the sequence you set out to get before flipping.

In the same way, its incorrect to narrow our search only to Mr. Comey and Mr. McCabe, because its likely wed be examining these probabilities if we learned that two other notable political enemies of an administration were audited instead of these two men.

A better question is: What is the likelihood that two or more people like Mr. Comey and Mr. McCabe would be audited over this period?

Should this group of people include any two top F.B.I. officials? Any two top Department of Justice officials? Its this framing a subjective decision rather than a factual one that most drives any probability estimate, more than any choice of statistical distribution or sampling weights.

Here is a chart of the probability our equation yields at different choices for the number of red marbles, ranging from two (Mr. Comey and Mr. McCabe and no one else) to 400 (a conservative estimate of the number of Americans Mr. Trump insulted by name on Twitter since beginning his run for the presidency).

The probability increases drastically with the choice of who should be considered a red marble alongside Mr. Comey and Mr. McCabe.

The point is not to decide on a number but to recognize that our choice of group size is what drives our answer. Although some guesses are certainly better than others, many choices are defensible.

Now lets try to narrow down something a touch more realistic, and return to some of the things we ignored in our simple interpretation of this problem.

First, the two men were not audited for the same year. By widening our scope to cover the three-year span from 2017 to 2019, our resulting probabilities increase significantly. This is straightforward: If a person has a certain chance of being audited in a given year, more years means more opportunities to be audited.

Second, we are interested only in the probability that at least two people are chosen. We will not consider the probability that the same person is picked twice; it seems unlikely given that the audits can stretch out over a year, according to Mr. Comeys account. Note that we are looking at the probability of at least two people being selected, not precisely two, since it would also be significant if three or more individuals from a group were chosen.

Finally, the I.R.S. does not select people in truly random fashion. Instead, the agency tends to select some kinds of taxpayers, including high earners, more often than others. For the 2001 tax year, the N.R.P. sample included returns from people around the 90th percentile of income at about 1.7 times the rate one would expect were returns chosen independently from earnings. That rate spiked through the highest income ranks, so that people with income in the top 0.5 percent were more than 10 times as likely to be in the sample as someone closer to the median income.

We can probably assume that any group of Mr. Trumps enemies would earn more than a random sample of Americans. But we cannot realistically estimate the complete incomes of everyone in our group in every year. We also know that the I.R.S. has considered other factors in its sampling, such as the type of returns that taxpayers file, and that sampling methods can change year to year. This leaves us with little in the way of guidance for how to match the I.R.S.s methods. As such, we will leave our estimates unweighted by income. As a back-of-the-envelope exercise, if you are worried about how income affects these results, you can double the resulting probability if you think the members of a group have very high earnings, and multiply it by 10 if you think theyre extraordinarily rich.

Incorporating those choices, the table below provides some estimated probabilities depending on the group size being considered.

Alternatively, if our choices are not satisfactory, we created a simple calculator for you to make your own probabilities:

So which estimate is correct?

Most realistic outputs of this equation could accurately be described as very rare or even extraordinarily rare, yet none is proof of wrongdoing.

Its a little like the irresistible force and the immovable object, said Andrew Gelman, a professor of statistics and political science at Columbia University, when told in the abstract about this exercise. On the one hand, youre saying its completely random. On the other hand, you suspect its not.

Mr. Gelman, like every other statistician who spoke with The Times about this problem, said the biggest hurdle was not any of the details but defining the question itself.

When we try to calculate the probability of a given event because we suspect it may not be random, we end up in the complicated position of trying to imagine how we would have predicted the likelihood of the event before it happened, said David Spiegelhalter. He heads the Winton Centre for Risk and Evidence Communication at the University of Cambridge, an organization dedicated to improving the way quantitative evidence is used in society.

The math is easy, he said, but formulating the question is tricky, bordering on meaningless, in large part because of how hard it is to pin down the group we care about.

Whats the chance of this happening? is an easy statement to make, he said. Its a familiar statement to make. But, actually, its a very difficult question to answer.

Math has its limits. The point of trying to estimate a probability such as this one, Mr. Gelman said, is not to put too much stock in the numbers, but to let the result push you to find out more.

In this case, the best question is not one with an answer you can look up in a statistics textbook.

Instead, Mr. Gelman said, the question to pose is: Whats going on?

Matthew Cullen contributed reporting.

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Comey and McCabe Audits: How Likely That They Were a Coincidence? - The New York Times

E3 2023 Will Return Headed by PAX Organizer With Promise of Titanic AAA Reveals – PlayStation LifeStyle

ReedPop, the production company behind PAX, will be bringing back E3 2023 in partnership with the ESA (Entertainment Software Association). The veteran event host, also in charge of New York Comic Con and Star Wars Celebration, promises that next years E3 will be a week of titanic AAA reveals and earth-shaking world premieres. This news lends more credence to the ESAs prior statement that E3 2023 would have an in-person event.

Unlike the past several E3 showcases which were either cancelled or only had a digital version of the event, ReedPop plans E3 2013 to keep the digital showcase along with in-person consumer components, according to a press release. Lance Fensterman, President of ReedPop, is excited to be able to give E3 a much-needed comeback:

Its a tremendous honor and privilege for ReedPop to take on the responsibility of bringing E3 back in 2023. With the support and endorsement of the ESA, were going to build a world-class event to serve the global gaming industry in new and broader ways than we already do at ReedPop through our portfolio of world-leading events and web sites.

Kyle Marsden-Kish, ReedPop Global VP of Gaming, will lead the team responsible for the E3 2023 and promises that it will be recognizably epic and a return to form that honors whats always worked. ESA President Stanley Pierre-Louis is looking forward to having ReedPops assistance with its world-class talent and a keen understanding of the video game industry.

While its unclear if E3 2023 will be open to the public, media registration for the event will start in late 2022. ReedPop will provide more information on the events schedules, exhibitors, and travel guides at a later date.

These past few years, numerous publishers and developers have established relationships withGeoff Keighleys Summer Game Fest, which is also planning a larger in-person event in 2023, while E3 has been absent or diminished due to the pandemic and other reasons. So it will require quite an effort from ReedPop and ESA to revitalize the former premier video gaming event in the year, but it appears that E3 2023s return is more credible than before.

In other news, Rockstar Games admits that Red Dead Online will be affected by GTA 6 development, and the November God of War release date is best for team to avoid crunch.

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E3 2023 Will Return Headed by PAX Organizer With Promise of Titanic AAA Reveals - PlayStation LifeStyle

Aaron Judge out of Yankees’ lineup vs. Red Sox with calf ‘soreness’ – New York Post

BOSTON Aaron Judge was held out of Thursdays series-opening, 6-5 win over the Red Sox due to lower-body soreness, Aaron Boone said specifically his calves, something the slugger has dealt with in prior seasons.

Judge said hes been dealing with the discomfort was stuff Ive been feeling for a week and said his absence was just precautionary.

The Yankees exited the victory with a 15-game edge over Boston and a 14/-game lead on the second-place Rays in the AL East, but can still hardly afford to lose Judge for an extended period of time. Both Boone and general manager Brian Cashman said Thursday they expect it to be a day-to-day situation.

The last couple nights there was tightness in his lower calf, Boone said before the game at Fenway Park. The idea is for him to be back in there [Friday]. Its not something Im overly concerned about. Its more important to get out ahead of it and make sure it doesnt turn into something big. Its not something we wanted to mess around with.

Certainly not with a sizable lead in the division and with Judge in the midst of an MVP-caliber season.

Judge added playing center field has nothing to do with the soreness.

After being given a scheduled day off Sunday in Cleveland, when he was limited to a pinch-hit appearance in a loss to the Guardians, the Yankees had an off day on Monday before Judge played both games in Pittsburgh.

Hes grinding through a lot in this half [of the season], Boone said. Well make sure its not a bigger issue. You dont want to mess with it, especially where we are in the season.

On Wednesday, Judge hit a grand slam for his MLB-best 30th homer.

With the season hes having, Judge has been at the forefront of the AL MVP conversation, along with the Angels Shohei Ohtani, and Cashman said he was pulling for Judge to win it as he potentially heads towards free agency.

Obviously, no one wants him to win the MVP more than we do, Cashman said. We want our players to be the best they can possibly be and hes standing tall. I look forward to him leading us the whole way, hopefully.

Judge had been 2-for-16 before his three-hit night in Pittsburgh on Wednesday, which included a grand slam.

Hes been as integral as anyone to the Yankees improvement over last season, and Cashman said he was happy to avoid an arbitration hearing with the star by agreeing to a $19 million deal for this season, with Judge having an opportunity to earn $500,000 in bonuses as World Series MVP and, yes, AL MVP.

Its nice to get something like that behind you, Cashman said of arbitration.

And he reiterated that there would be no public discussions of any potential extension talks between the two sides during the season, per Judges wishes.

That doesnt mean a conversation will or will not take place, the GM said.

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Aaron Judge out of Yankees' lineup vs. Red Sox with calf 'soreness' - New York Post

OPINION: The legislature heads home now what? – The Richmond Observer

The North Carolina General Assembly brought its 2022 short session to a close last week. Well, at least, it kinda, sorta did.

Unlike in decades gone by in which the legislature generally adjourned in early summer, not to return until the following year, the current leadership on Jones Street prefers to keep the states supposedly part-time lawmakers yo-yoing back and forth to the state capital. And so it is that the adjournment resolution approved by both houses last week calls for senators and representatives to return to Raleigh for a series of mini-sessions that will take up at least part of each of the six months remaining in the year.

As for what legislators will do during those half dozen forays back into the Legislative Building, the resolution lists a number of possibilities, including consideration of gubernatorial vetoes, so-called conference reports on bills that have been at issue between the two houses, and rather ominously, any bills relating to election laws. Those who have followed the General Assembly in recent years are well aware that resolutions like this serve more as guideposts than hard and fast restrictions.

As a practical matter, lawmakers will consider whatever Republican leaders want to consider and think they have the votes to pass. And this could be bad news, good news, or both.

Among the most worrisome possibilities is that leaders will once again renew their decade-long commitment to partisan gerrymandering and voter suppression. Buoyed by the U.S. Supreme Courts deeply disturbing announcement last week that it will consider their frightening argument that state courts should be powerless to review the election law decisions of state legislatures, it seems at least plausible that Republican leaders will try at some point to pass some new limits on voting, and perhaps, even try to rearrange the states congressional district maps to provide House Speaker Tim Moore with his long-coveted congressional district.

In the hope springs eternal department, it seems there remains at least a chance that the legislature could revisit Medicaid expansion in order to, at long last, close the states yawning health insurance coverage gap. While Senate and House Republicans remained at loggerheads at last report on the specifics of what should and should not be included in such legislation, its clear that they continue to inch, ever so slowly and painfully, in the right direction on this front. And now that the majority of lawmakers are on record as having endorsed some version of this widely popular concept, its hard to imagine that it will remain stuck in suspended animation for too much longer.

Sadly, however, on most other important fronts, the prospects for meaningful progress look distressingly slim.

Despite incremental headway in Washington in which North Carolinas GOP senators played an important role, passage of meaningful gun safety laws even a modest red flag bill of the kind specifically promoted by Sens. Tillis and Burr seems all but impossible.

And medical marijuana another issue on which many Republican lawmakers have experienced a welcome epiphany of late also appears stalled for the foreseeable future.

And then, of course, there is the overarching issue of state spending on core public services and structures. While Republican legislative leaders did, at almost the last minute, push through a new, secretly crafted budget bill, the proposal comes up woefully short in numerous ways.

First and foremost, despite the presence of a multi-billion-dollar reserve, the proposal fails yet again to comply with longstanding court directives in the Leandro case to adequately fund the states public schools. As veteran education policy analyst Kris Nordstrom detailed last week, the budget proposals much-ballyhooed teacher pay raises are actually more akin to cuts when one adjusts for inflation. The same is true for supposed pay increases for state employees.

And while its true that the measure, for once, includes no new regressive tax cuts that would further shift the responsibility for funding government away from rich individuals and large, profitable corporations, and onto low- and moderate-income households, this is only because multiple cuts of such an ilk were already scheduled by previous legislative action cuts that will reduce state revenues by $1.5 billion in 2023.

Now add to this that the budget bill is packed with pork spending on dozens of highly questionable items ($15 million for the ACC?!), and does little, if anything, to aid families struggling to recover from the pandemic recession, and the proposal looks maddeningly familiar.

The bottom line: Even with the modest check on their power thats provided by a Democratic governor whose vetoes they cannot currently override, North Carolina Republican lawmakers show few signs of backing off from the aggressive right-wing agenda thats marked their 11-plus years in power. And with a mid-term election looming that favors the party not in control of the White House, the chief policy question for the years second half appears to be whether North Carolinians will see more of the same or the prelude to something even more darkly ambitious.

Rob Schofield, director of NC Policy Watch, has three decades of experience as a lawyer, lobbyist, writer and commentator. Republished from NCPolicyWatch.org.

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OPINION: The legislature heads home now what? - The Richmond Observer

Red Sox SP Chris Sale Expected to Return from Rib Injury for Tuesday Start vs. Rays – Bleacher Report

The wait for Boston Red Sox starting pitcher Chris Sale's season debut could end soon.

Red Sox manager Alex Cora told reporters that Sale is set to pitch Tuesday "somewhere" as he makes his return from a rib injury that has kept him out for the first few months of the season.

Cora added, "Theres a good chance hell pitch with us."

Sale made a rehab start for the Triple-A Worcester Red Sox on Wednesday in a 4-2 loss to the Scranton/Wilkes-Barre RailRiders. The 33-year-old allowed five walks, three hits and one unearned run while notching five strikeouts in 3.2 innings.

After exiting the game, Sale apparently wasn't happy with his performance as he had an angry outburst in the clubhouse tunnel. On Thursday, Sale apologized for what he called a "seven-year-old temper tantrum" and added he "acted like an idiot" during the incident.

A seven-time All-Star, Sale was once the ace of Boston's pitching staff. He underwent Tommy John surgery in March 2020 and missed the entire pandemic-shortened season. He returned to the mound in August 2021, posting a 5-1 record with a 3.16 ERA and 52 strikeouts in nine starts.

Sale looked poised for a bounce-back season in 2022, but he suffered a stress fracture in his rib cage in March that has kept him sidelined.

The Red Sox got off to a slow start this season, but they have since righted the ship and are tied for second in the AL East with a 45-37 record. A return by Sale is sure to benefit the team as the second half of the season approaches.

Boston begins a four-game series against the rival New York Yankees on Thursday at Fenway Park and then heads to Tampa on Monday for four games against the Rays.

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Willow Crossing Trail, Coconino National Forest: How to find it – The Arizona Republic

Mare Czinar| Special for The Republic

Tucked into a sliver of space in the canyon-addled watershed of West Clear Creek, Willow Valley is a calm oasis of green in awater-carved landscape.

Within the shallow canyon, a sketchy trail known as Willow Crossing descends from an airy plateau littered with toppled trees from past wildfires, wildflower meadows and a smattering of tall pines into a narrow canyon with a totally different character.

Bound by chalky limestone walls chiseled into layer-cake-like formations, the ecozone inside the miniMogollon Rim gorge transforms from a sunny, lightly wooded mesa into a jungle of greenery.

This tiny Eden isnt easy to find or follow, but careful explorers are rewarded with many surprises.

Near Payson: This hike is a not-too-tough way to reach the East Verde River

A series of rough dirt roads near Clints Well in Coconino National Forest northeast of West Clear Creek Wildernesslead to a barely-there trailhead. Four-wheel drive is recommended.

To pick up the historic route, follow the old barbed wire fence to a gate near the edge of the canyon. Pass the gate (close it behind you) and pick up the obvious path leading downhill.

Near Sedona: This favorite hike has flowers and iconic red-rock formations

As the short, rocky trail descends among hairy stands of common mullein that can sprout corn-like shoots to over 6 feet high, riparian vegetation closes in on the trail.

Gambel oaks, boxelder, New Mexico locust and a tangle of the eponymous willow trees clutter the slopes. Where the trail bottoms out at a drainage, look for water-loving wildflowers and shrubs like larkspur, wild roses and red-osier dogwood.

Like all crossing trails on the Rim, this one hops the drainage and heads up to the opposite lip of the canyon. In between the rims, the hikes signature attraction stands nearly obscured by tree cover and wild grapevines woven among thickets and boulders.

A delicate natural arch carved from the canyons sedimentary rock walls forms a fragile bridge over a fold in the disintegrating wall, revealing a glimpse of sky and ponderosa pines 400 feet above.

Length: 2-3miles round trip.

Rating: Moderate.

Elevation:6,400-6,800 feet.

Getting there:From Payson, go north on State Route 87 to Lake Mary Road (County Road 3). Turn left and go northto Forest Road 81 (past mile marker297). Turn left and go3.1 miles to FR81E. Set your odometer, thengo left on FR 81E for 1.14 miles to FR 9366M an easy-to-miss, unmarked dirt road on the left. Go 0.5 mileon FR 9366M to a cattle guard and gate. The trailhead is just past the gate on the left near the generic trailsign and rock cairns. A high-clearance vehicle is recommended.

Details:Coconino National Forest,https://www.fs.usda.gov/coconino.

Read more of Mare Czinar's hikes athttp://arizonahiking.blogspot.com.

Support local journalism. Subscribe to azcentral.com today.

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Willow Crossing Trail, Coconino National Forest: How to find it - The Arizona Republic

Visions of Jane Eyre: On Mothers, Labor, and the Places Children Hide – Literary Hub

Crying does not indicate that you are weak.Since birth, it has always been a sign that you are alive.Charlotte Brnte*

A friend of mine tells me she remembers the womb. The womb was a red room, and in it, only a mirror made of blood in a frame made of tissue in which my friend watched her face become her face.

I heard how a woman I work with witnessed her own birth (though shes well past forty), by participating in a ritual: Buddhist meditation, Native American peyote, Catholic transubstantiationwhatever it was in whatever combinationshe was shown an apparition of the red room turned inside out, the mirror made of blood shattering, the frame that held the mirror ripped to shreds.

She was terrified, also in awe. Trembling, weeping, she called her mom and said, Mom, thank you. Her mom replied, Honey, Im sorry you had to see that.

Jane Eyre was locked in a red room when she was naughty. It shared some architectural details with other red rooms, but it was into its drawers and secret crevices that Mrs. Reed stuffed remembrances, not of her children, but of her husband and her money. Weve all heard those legends about women who cram guns into their vaginas and are surprised when the guns go off. I might say the same of Mrs. Reed. By cordoning off her red room for punishment, she condemns Jane to a life of apprehension.

Looking back on her time at Gateshead Hall and in particular the red room, Jane says, The housemaid alone came here on Saturdays, to wipe from the mirrors and the furniture a weeks quiet dust. Where Jane might have found comfort, she finds divers parchments. Where she might have found a mothers heart, she finds a painted miniature. Isnt it rumored that Queen Elizabeth I carried with hereven unto her deathbeda miniature of her own criminal mother? When Jane is locked inside the red room, shes forced to recall what she doesnt remember. How horrible. For both my friend who remembered and my coworker who saw the insides of their mothers, their mothers hearts appeared as enormous as the Koh-i-Noor diamond, and as inelegantly cut.

Of course, a fetus wouldnt be able to see her mothers heart; this is what I mean when I say no memory and no vision can ever be absolutely trueat least not scientifically. The insides of our mothers bodies are the only places that are most certainly past.

From then on, from there on, every room is just an echo of that first, red room, and we drift through them as women drifted through the Great Exhibition of 1851, pausing to look at the Koh-i-Noor no matter what humble station they occupied, whether kitchen maids or schoolteachers, daughters of businessmen or bakers. They stopped and looked because that diamond was a prize theyd never get their fingers on, or get on their fingers. Or wear on their heads. Or sparkling at their throats. That diamond is a memento of underground transformation, unseen processes proving theres still mystery abroad, but to own it requires the luck of a good birth.

After the exhibition was over, Prince Albert hired a jeweler to recut the Koh-i-Noor into sixty-six facets, and in the process a large percentage of the diamonds caret-count was lost. He was frustrated by that fact, but he softened when he saw the Koh-i-Noor nestled inside the queens brooch, and how what it lacked in heft it gained in light refraction. A mothers heart, over time, is bowdlerized to meet the latest fashion.

The Great Exhibition of 1851 left in its wake a cache of oddities with nowhere to go. These days, call an artist after the show and shell come fetch her paintings. Naturally, the British refused to telegraph India and tell it to come get its sovereignty. So, in order to house unclaimed artifacts, new museums were built across Londona project spearheaded by Prince Albert himself, whose crowning achievement would become the Victoria and Albert Museum in South Kensington.

In Bethnal Green another building went up, first as a matter of storage and later as means of educating the neighborhoods working poor. Its black-and-white tile floors were made by women prisoners in Eppingthe fish-scale motif meant to give wayward female inmates a sense of purpose and pride, and to delight, even hypnotize, museumgoers into a state of intellectual curiosity.

But many of these criminal women were mothers and sometimes fudged the pattern, until, well into the 20th century, the Bethnal Green Museum was renamed the Museum of Childhoodnot a childrens museum in the way we understand it (STEM activities, interactive exhibits) but a museum about childhood.

Childhood to the English must be sad. There are objects in this museum that existed before childhood existed. But even before childhood existed, people must have considered how their offspring liked dolls, and how those dolls liked little houses. They must have discovered how their offspring liked to play at things like tea parties and matrimony, meanness and profiteering. They considered their offsprings affinity for daydreams, aliases, and alliances. One child, for example, made his mother wake him twice each morning. The first time he would be himself, and the second time hed be a fairy child lost in the wood. The mother grew exasperated after months of this, and so employed an automaton-mother to take over, thus saving time and psychic energy.

This mother is now on display at the Museum of Childhood, along with a picture book in which Circle, Square, and Triangle are playing hide and seek. Circle tells the others not to hide behind her waterfall, but Triangle is a rule-breaker and hides there anyway. When Circle searches for Triangle, she encounters another shape in the darkness, an unknown shape that must be conjured by her imagination, and soif were being honestthe conjuring of a shape out of perceived darkness is just another way of saying I own you.

II. I Shall Rise Again

We might say these are my children or this is my country, but in saying so were only fooling ourselves. In another heartbreaking act of foolishness, a woman in Korea, through the magic of virtual reality, was able to see her dead child again.

In the mothers VR goggles, her daughterwho died of leukemia in 2016had only been in a park, crouching behind a camphor tree. Now she materializes, leaving off her long game of hide-and-seek. Wasnt it Marianne Moore who said poetry is imaginary gardens with real toads in them? If neither the girl nor the park is real, then the camphor must bethe camphor tree behind which the imaginary girl hides. But the girl used to be a real girl, and this is the scope of her mothers poetry:

Mom, where have you been? she asks. Ive missed you a lot. Have you missed me?

I dont know whether the game is played solely in the park, or if it moves inside, into a house, maybe the very house where the mother and daughter lived together, or maybe some other housethe palace little girls dream about, filled with enough rooms for a most sumptuous game of hiding and seeking: wardrobes, attics, off-limit wings. She might hide inside a red room.

She might tiptoe barefoot down a back stair, get lost in a box of very old things, never to be heard from again, only to rise again, now in Jane Eyres Lowood School, built to accommodate perspicuous observation but, against all odds, allowing for fine, shimmering secrets like silkworms in a lacquered box. Just out of sight, around corners, hidden inside the high rhetoric of religious obedience, in the shadowy oligopticon of Lowoods communal bedroom, girls have their private visions, especially Jane Eyre herself who

wandered as usual among the forms and tables and laughing groups without a companion, yet not feeling lonely: when I passed the windows, I now and then lifted a blind, and looked out.

I remember the tumult of school. I was meant to be formed by teachers scrutiny, but really it was the diagonal looks, the trapezoids of laughing groups, notes passed surreptitiously in the shifting hierarchy children build, that gave me my shape, that and occasional glimpses out windows; through them, the scenes diegesis becomes a collection of disconsolate images, my bored, sullen reflection pasted onto snow grassstreet, whatever world it is. No wonder I turned to poetry.

And the oligopticon is poetrys friend, for unlike the panopticon it resists absolute surveillance, offering a space where not everything can be seen, but what can be seen is seen at close range: girlhood friendships, puberty, death, the mingling of social classes, democratic exchange. At Lowood, Jane Eyre sees the minute details of disease, malnutrition, abuse, hears conversations unspool themselves in doublespeak, learns to play hide-and-seek.

The oligopticon is French sociologist Bruno Latours term, coined in 2005 to describe the smaller, intimate spaces inside which larger systems are reified. The oligopticon seems to me an opportunity for both submission and resistance; if, for instance, Lowoods intention is to solidify longstanding notions about the spiritual fragility of children generally and lower-class female children specifically, its administration will look for and find that fragility.

If, instead, the girls themselves want to see spiritual bravery, then theyll see it, if only in a very small, three-inch-long mirror, for example. If they want to see a girls capacity to learn, to demonstrate complexity of thought, strength of character, then theyll see that too, and, little by little, connections, however tremulous, will be made. Little by little, the master narrative will change.

Its inside the oligopticon that Jane witnesses Helen Burnss deathnot just witnesses but absorbs it, hugging it close to her own body. This is Helen Burns who

looks as if she were thinking of something beyond her punishment beyond her situation: of something not round her nor before her. I have heard of day-dreamsis she in a day-dream now? Her eyes are fixed on the floor, but I am sure they do not see ither sight seems turned in, gone down into her heart: she is looking at what she can remember, I believe; not at what is really present.

Poor Jane. Shes only just heard of day-dreamswhat my daughter calls the thing she does at night to put herself to sleep, the seeing-and-not-seeing she engages in. But engages is not really the right wordits more passive than that, like looking out a window onto a snowy street and letting the eyes cross slightly, lose focus.

After Helen dies, after Jane is lifted, weeping and brokenhearted, from the bed they shared, she tells us,

Her grave is in Brocklebridge churchyard: for fifteen years after her death it was only covered by a grassy mound; but now a grey marble tablet marks the spot, inscribed with her name, and the word Resurgam.

The tablets inscription means resurrection in the Christian sense (as a gift bestowed), but the Latin is translated, I will rise again, giving Helen herself some agency in the matter. Maybe Helen is telling Jane shell come out of hiding someday. Maybe Helen is speaking directly to Jane the skeptic who wondered aloud while Helen was still living, What is God? to which Helen responded, My maker and yours, who will never destroy what He created.

The creator of the city of toys in Consonno, Italy, never destroyed it, only abandoned it, though he (Count Mario Bagno) razed the original medieval town in order to build it. When bulldozers began demolition in 1965, the residents had little, if any, notice. Several residents reported learning of the plans when they first heard the sounds of the bulldozer engines. The villagers gathered what they could and fled, narrowly escaping with belongings before the walls came down.

This account comes from a website called Sometimes Interesting, which attempts to uncover the history of the abandoned, forgotten, and unexplaineda triptych of words each in its own sad, little frame, hung in the sky for Consonnos refugees to point to. See, they said. See how they took our home and gave us daydreams instead?

All thats left of the first Consonno is its 13th-century church and its little graveyard filled with so many Helen Burnses, so many promises of resurrections, that the earth itself decided to show; having been leveled by dynamite, its rock pulverized, the earth let loose landslides so devastating that Bagnos second Consonno was deserted and left to rot deep in Lombardy, plans for Italys folly-rich playground permanently delayed, until they came. They came to Count Bagnos Italian Las Vegas, his fantasyland, his city of toys, to spray-paint graffiti on Doric columns. To have sex on top of cannons. To dance in empty storefronts.

As Helen Burns says, no creator would (absolutely) destroy what he created, and if we know where to look, the fountains, pagodas, the minaret-topped arcade reveal themselves, rising from the subalpine forest like the spires of a church inside which there is, as Bruno Latour tells us, no control and no all-powerful creator, eitherno more God than manbut there is care, scruple, cautiousness, attention, contemplation, hesitation and revival.

In the context of Consonno what I mean is this: graffiti, bird shit, bonfire parties in the ashram of an old hotel lobby, the ritual of discovery and revivalas if every pilgrim is the first to see and recognize the place for what it isis the gorgeous reverse of a shining city on a hill. Care, scruple, cautiousness, et cetera: these are intimacies gone unseen panoramically, gone unrewarded systematically, but revealed by delicate negotiations between whats hidden and whats found.

In 2017 the Nascondino World Championship in hide-and-seek was held at Consonno, followed by hidden concerts in the city of toys ruined buildings, though they remained structurally unsound and possibly dangerous, rendering every happened-upon musician as vulnerable as a child. The games players themselves werent children, though they had been once and wanted to be again, all four hundred of them confined to an obstacle course just beyond Consonnoa rolling lawn with hay bales, plastic rocks, barriers for hiding behind, and, of course, trees: cypress, cherry, laurel, spruce. There were food trucks, live feeds, men and women decorating their bodies with dirt and leaves, announcers giving the play-by-play in lush northern Italian accents.

And watching the footage from very far away, I can still see the specific joy in their faces; everything else falls away. I see a young woman crouching behind a pile of firewood tapped on the head by a young man sprinting past her, and sheshining in her Day-Glo shortsrises to full height and strides, disappointed surely but laughing, to center field, shaking out her long hair and shouting, Ti sono mancato? Ti sono mancato? And all of Consonnothe ancient town thats gone, the newer town only half there, and the town yet to be builtcalls back, S, mia cara! S, and she, simply by rising, raises me with her.

III. Even in Arcadia, Here I Am

The blemishes and irregularities in the floor at the Museum of Childhood are likely glossed over by the casual visitor, but if one looks closely, every line begins to move. Every tile is, in some way, wrong.

Inmate Florence Maybrick said, In the winter the prisoners get up in the dark, and breakfast in the dark, to save the expense of gas. The sense of touch becomes very acute, as so much has to be done without light. Until I had served three years of my sentence, I had not been allowed to see my own face. Then a looking-glass, three inches long, was placed in my cell.

When the mirror arrived at last, it only showed Maybrick pieces of herselfsome forehead, a slice of chindepending on the tilt of her head. The prisoners at Epping who mended clothes and made tiles were missing their own mothers, their own children, and some were tossed into solitary confinement where the only thing they saw was the days residue on the back side of an eyelid.

Looking into her mirror, Maybrick saw, instead of a nose or a mouth, a stitch, then another stitch. The women who made the tiles saw, instead of a cheek or a brow, the kiln and the fire. The fire and the kiln. No wonder the floors pattern fails at precision. No wonder they couldnt see the overall effect. They werent, in fact, allowed to.

When Jane Eyre is tossed into the red room, she sees dust on the mirror instead of herself. She sees the massive bed like a tabernacle and a white chair like a pale throne. She sees the divers parchments and jewel-casketthe whole room under the spell of the last words that kept it so lonely. She means Mrs. Reeds miniature of her dead husbandnot words at all, but an icon, though she requires words to describe it. It isnt a stretch to imagine Jane is thrown into a kind of church, made to stare at its symbols, then articulate them in the only way she can. Shes an outsider suddenly inside, trying to remember something there is, in fact, no way to remember. Like the womb. Like the mothers heart.

Only in this moment, Jane is trying to remember a god shed never met, and the red room as that gods inner sanctum. Its terrifying to her, blinding in its effect. I suppose I had a species of fit: unconsciousness closed the scene, she tells us, then a new chapter begins. Its a chapter about losing one kind of vision but gaining another.

Once, during Mass, I followed my classmates up to the altar and let the priest drop a wafer in my hand. Body of Christ, he said, and made the sign of the cross over me. I put the wafer in my mouth, letting it dissolve rather than chewing; this is how I saw the other kids do it.

It wasnt until a few days later that I learned Id committed a sin. I wasnt confirmed. I had no right to take the wafer, put it in my mouth, and let it dissolve, as the other kids had done. Id been, for all intents and purposes, an outsider suddenly inside, trying to remember something there is, in fact, no way to remember. And the effect on me was a species of fitnamely, the feeling that I was a splinter of glass under the skin, an irritant in the eye born of my own badness, a terrible girl.

After thismy foundational mistakeI felt myself irrevocably described as an outsider whod somehow wormed her way in. And if, as the priest said, Id indeed eaten the body of Christwhy, then, Christ was swimming inside a sinner, my body holding his body in a sort of prison, and when he looked in my own red rooms mirror, he saw only pieces of himself. How could he be whole now, in me, here?

Erwin Panofsky, German American art historian and refugee, wrote a monograph on Arcadia, that miraculous pastoral place, arguing that the Latin phrase Et in Arcadia ego has been wrongly translated by some poets and artists as I once lived in Arcadia too, when it was King George IIIthat madmanwho said it actually means, Even in Arcadia, here I am. Panofsky tells us that, according to Georges interpretation, in Arcadia human suffering and superhumanly perfect surroundings create a dissonance. This dissonance, once felt, had to be resolved, and it was resolved in that vespertinal mixture of sadness and tranquility.

But resolution is a forced conversion, or, at best, false speech in a lonely room. The dissonance Panofsky describes is love, and love must be allowed to spread, to seep under doorways, over dormers, to creep inside the bowdlerized heart, unconfined and unconfirmed, given access to everywhere.

But since theres no such place as everywhere, someone gave it an address, called it the Museum of Childhood, and now displays its impressions behind glass. It categorizes its holdings not necessarily by time period but by kind: all the sight gags are grouped togetherthe 19th centurys myriorama, thaumatrope, and kaleidoscope along with the 20th centurys View-Master. And all the dollsan ancient wooden figure, an 1850s Autoperipatetikos (the Walking Doll), an 1880s Johnny the Dunce that plays a sad tune on his toy violin, and a 1980s Cabbage Patch baby with a face like a prune.

It was a tranquil Christmas morning in the 1980s when I walked up the hill with my new Cabbage Patch doll to show Melanie, who answered the door holding her own Cabbage Patch doll. I was looking into a very sad mirror.

And it was in the 1980s when nurses came to elementary schools and systematically screened children for scoliosis, though theyd been doing it for nearly a century, first to catch disease-made spinal curves, then to surveil for the idiopathic version, meaning: no discernible cause. Because no one knows where idiopathic conditions come from, they are prime opportunities for moralizing. Government programs branded scoliosis a sort of slippery slope, a dangerous curve that with time and lack of intervention might become a deeper twist, a disastrous turn of events that, like drugs or sex, could lead to severe pain, maybe even death. I was never consigned to a back brace, though I heard some kids were. Looking at my X-ray was like looking into a very sad mirror.

In 2014 when an anesthesiologist felt my back before plunging the epidural needle deep in the middle of the night, I was reminded that my spine isnt right. Did anyone ever tell you, he said, that you have Because of my crooked spine, the epidural didnt take, and I spent all night vibrating in paina pain so righteous that when I closed my eyes, I saw red, red, red, red, pulsing. I thought to myself then, I really must write a book someday. Itll be about Jane Eyre and mirrors and wombs and toys and researchers in China who constructed a classroom made entirely of glass because, they hypothesized, exposure to natural light would help prevent myopia in children, and it workedsomewhat.

But the classroom was hot, sometimes uncomfortably so, and the children grew luminous, and the pages of their books far too bright to see. From the outside, their parents looked in (because they could) and saw the children put their hands over their eyes. Bet you cant see me now, the children said, and though all the parents agreed that they in fact could see their children, they lied and said (because this is a game, after all) that they couldnt, calling out, Where, oh where did my little baby go? and with that, their childrenabsolutely and without flourishvanished from view.

________________________________________

This essay was originally published in Issue 113 of Image under the title Labor.

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Visions of Jane Eyre: On Mothers, Labor, and the Places Children Hide - Literary Hub

Schools: the big problems facing heads – Tes

It has been easy, this week, to get suckered into a pre-occupation with Westminsters collapse and forget that many dont have the time, inclination or reason to watch every turn and stall.

A good example: on Tuesday, as the first resignations hit and the education secretary departed, most teachers were too busy plugging the holes in a broken system to ruminate upon Nadhim Zahawis real reasons for ditching the Department for Education (DfE)in favour of the Treasury. They were doing the same when Michelle Donelan resigned from the post after just 35 hours in the job and James Cleverly then became the third education secretary in a week. .

Of course, any event that leads to a DfE empty of ministers (barring Baroness Barran) is a disgrace. And, yes, I could spend this leader writing about that. But to do so would be of no real help to those who work in schools.As a trade publication, sometimes our role is to work within the political arena to force transparency and push for change. But right now, our role must be to highlight the desperate situation schools are in and shout about it repeatedly until people listen.

Politics so often side-steps, drowns out and dilutes these issues. Right now, we have to tell it like it is, in all its raw brutality, so they cannot be ignored.So if parts of this leader feel repetitive, I make no apology for it.

Lets start with Covid. It ravaged education - through staff and pupil absence, through the collapse of support services, through long-term illness, and through a complete change in not just the way teaching had to happen but the willingness of some to be taught. The government simply hasnt got to grips with the scale of the problem and the damage done, nor the ongoing disruption.

And thats not because school leaders havent told them. Our recent Education Insights Expert Panel webinar- with a multi-academy trust leader, a headteacher and a special school principal - lays out clearly what many have been saying for some time. Wider society needs to recognise that schools are in desperate need of help. The only reason things are not worse (as our reporter Matilda Martin pointed out in her Twitter thread on the absolute shambles of the SATs process this year) is because school staff are going above and beyond.

Then there is the funding. Schools simply dont have enough money. Even those not in the red predict that energy price rises, non-educational spend on filling social or health service gaps, building costs, extra intervention spend owing to Covid impacts and supply costs resulting from open vacancies will send them into financial trouble.

Quite simply, calling it a school budget is inaccurate: that money is now meeting health, social, community, wellbeing and outreach needs. It simply cant go on.

Recruitment and retention is a mess. There are not enough people who want to be teachers and there are not enough teachers currently doing the job who want to carry on. The early career framework and establishment of the Institute of Teaching are not likely to make enough difference to change this situation. The handling of the re-accreditation of initial teacher training providers will likely make it worse. Come September, some parents will find that their children dont have permanent teachers. The workforce experts will tell you that, in 2023, there will likely be even more parents in that situation.

And the special educational needs and disabilities (SEND) system? It has been abysmal for years and the SEND Review - which shows so much promise in fixing some of its worst problems - is likely now dead in the water. Children with additional needs will continue to suffer throughout school and their life chances post-school will continue to be poor, despite the best efforts of their teachers.

Each of these things alone should be a national scandal. But enough smoke has been poured out in the form of swerves and meaningless statements and distractions, that your average member of the public has no idea that things are this bad. Worse, they think its being overplayed.

The real danger now is that - with new faces and new teams coming into the DfE - once again, nothing will be done. It will take months for the complexities to be understood, months for ideas to form, months for proper consultation and, at the end of it, so many of the problems cited here will be left on the too complicated, too expensive, or I dont believe its that bad piles. And then the faces will change once more and it will all start again.

Of course politics is important. Of course it is at the root of the change needed to solve these problems. But sometimes the politics gets in the way. Sometimes we need to ignore the political distractions and keep saying the same thing, without wavering, until someone listens.

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Schools: the big problems facing heads - Tes

Gretchen Rossi Turns Heads With Four Of July Star-Spangled Bra Gretchen Rossi Turns Heads With Four Of July Star-Spangled Bra – Gretchen Rossi Turns…

Is Gretchen Rossi ready to celebrate the Fourth of July? She certainly seems so!

The Real Housewives of Orange County alum took to her Instagram page on Sunday to share a snap of her and her daughter, Skylar Gray Smiley, looking truly patriotic in red, white, and blue outfits!

On Sunday, the 43-year-old mom sported a stars-and-stripes bra with matching bottoms and topped off the look with red sneakers. She wore her blonde hair in loose waves around her shoulders and tied her hair back out of her face with a white ribbon. Her daughter, Skylar, looked equally festive in a red-and-white crop top and a denim jean skirt. She topped off the look with Western boots, star-shaped sunglasses, and blue ribbons around her pigtails.

Ready for the 4th of July Rossi captioned almost two identical shots of the two standing side by side. Love dressing up with my mini me! Her outfit is tagged in my highlight reels & my outfit is from @shopxthecloset.

Kelly Leventhal commented, Shes so cute.

Bravos Dina added, The little hand on her hip!

Lindsay Albanese wrote, Omg

Marysol Patton added, You two are so precious.

Lizzie Rovsek commented, Omg!!!! CUTENESS OVERLOAD!!!!

The cutest Happy 4th!! another follower commented.

Omg Sky is so adorable!! another wrote. You are too, of course.

So so cute! said another fan. Luv how did ur daughter hair

Could not be any cuter! another shared.

Two absolutely awesome beauties!!! another follower commented.

Plenty of fans chimed in to say, sHappy 4th weekend !

Last year, Gretchen Rossi continued to channel her patriotic vibes in an equally cute outfit! She donned a knit short-sleeve sweater stitched to look like the American flag over short white shorts. She again tied back her blonde hair with a bandana a red one this time and matching red sneakers.

Skylar traded out her Western boots for simple sneakers, along with heart-shaped sunglasses, dark slaps, and a red-and-white striped top.

Hope you all had a wonderful 4th of a July! Rossi wrote in an Instagram post on July 5, 2021. We are up at the lake with our family for the week & are having such a great time Slade took a bunch of fun pics of me & Sky just chilling at the local Jones Store.

I basically look the same in each picture but her different littles expressions in each picture just make me giggle! she added. We have so much fun together She wrapped up the post, saying, She is full of so much sass & personality #sogratefultoliveinamerica#lovetheUSA.

So freakin cute!!!!!!!!! one follower commented. Many fans echoed shouts of ADORABLE! Another called her snaps Precious!!

Wow. You and your daughter are fabulous. Well done maam! another follower wrote.

I love that sweater!!! said another fan.

America was blessed by these outfits another shared.

Ok the cutest mom/ daughter outfits ever! Love Skylars sun shades. Hope you enjoyed your 4th of July holiday!!! another wrote.

With so many stylish outfits in her closet, fans cant wait to see what kind of patriotic outfit Gretchen Rossi will don next year!

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Gretchen Rossi Turns Heads With Four Of July Star-Spangled Bra Gretchen Rossi Turns Heads With Four Of July Star-Spangled Bra - Gretchen Rossi Turns...

Rangers branded packaging has Newcastle fans scratching their heads as Castore ask them to ‘Follow Follow’ – Daily Record

Castore were reportedly forced to send out Rangers kits in bags without the club logo after claims that thousands were sabotaged while out for delivery to supporters by courier company Hermes.

Hermes launched a probe into the issue while the Ibrox clubs kit manufacturer offered a refund to those who were affected. But choosing to despatch the strips in packaging without the Rangers logo looks to have created a new problem, leaving the Liverpool-based company - who signed a five-year deal with the Light Blues - with quite a few spare bags.

And Newcastle United fans reckon Castore, run by brothers Tom and Phil Beahon, might just have discovered a solution for any excess packaging. The English Premier League side agreed a deal with the Merseyside company to produce their strip and some Magpies supporters have taken to social media to post images of their new kit arriving in RANGERS-branded bags.

One, sharing a picture a bag with the Gers Follow Follow slogan and the Ibrox clubs crest on the bag wrote on Twitter: @NUFC tops arrived today. Was worried that #castore had sent out the wrong strips before opening. Another, showing the Rangers crest on the despatch note, asked: Anyone elses Newcastle shirt come from Rangers Football Club?

Castore have come in for some criticism from Rangers fans since their deal which banked the Ibrox club around 4 million in their first season but were forced to apologise early on over quality control issues.

Commercial chief James Bisgrove addressed some of the issues at the time and said: The first year of the partnership had some fantastic highs but also threw up some challenges, later adding at the clubs AGM I think it hasnt been perfect, particularly at the beginning when we came out of Covid and there were certain issues with customer service.

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Rangers branded packaging has Newcastle fans scratching their heads as Castore ask them to 'Follow Follow' - Daily Record

Inflation never far away as PM Jacinda Ardern heads to Sydney to sell New Zealand – Stuff

SUNGMI KIM/Stuff

New Zealand Prime Minister Jacinda Ardern

As Prime Minister Jacinda Ardern prepares to fly to Sydney on Wednesday, the Reserve Bank of Australia delivered a reminder of the Covid-induced cost of living crunch back in New Zealand, lifting Australias official cash rate target by half a basis point to 1.35%.

Ardern said on Monday that she expected the scourge of inflation to be widely discussed on this trip. Australian Treasurer Jim Chalmers greeted the news of rate rises with a warning: dont expect things to improve quickly.

While the trajectory of rising interest rates was set before the election, this rate rise is another blow to workers and families already under significant cost of living pressure, Chalmers said.

Australias inflation grew by 2.1% in the first three months of the year, higher than New Zealands growth in the past quarter of 1.8%. And Chalmers thinks the cost of living will rise further still in Australia.

READ MORE:* Reserve Bank's interest rate ratchet will be new - and worrying - to a lot of voters* Sharemarket ends week at lowest level in more than 7 months* Covid 19: Government faces cost-of-living crunch as Auckland stuck in lockdown

When it comes to inflation, we expect it to get worse before it gets better and the Reserve Bank has flagged further rate rises, Chalmers said.

In comparison, Finance Minister Grant Robertson has leaned on Treasury and other forecasts of falling inflation in New Zealand.

Luke Malpass/Stuff

Jacinda Ardern and Victorian Premier Daniel Andrews.

Meanwhile, Ardern fielded a series of questions about both New Zealands immigration settings and Covid-19 as back in New Zealand Covid cases crept up towards the 10,000 mark.

Ardern will complete the trade-heavy part of her trip to Australia on Wednesday, giving a short speech at an unusual joint New Zealand-Australia tourism event and a New Zealand food and products launch at David Jones original flagship store in central Sydney.

For the Discover New campaign, New Zealand wares will take up a whole floor at the Sydney department store.

But inflation and Covid have never been far away on this trip whether it is shuttered shops in Australian cities, the continued fear of inflation or even of the daily Covid numbers.

Ardern was firm in her Governments view that, even with the hike in case numbers, the red traffic light setting was not required.

We have no expectation at this stage. We have recently done a review and decided to stay in the settings that we had, Ardern said while taking questions from media after meeting Victorian Premier Daniel Andrews.

The question here is, would gathering limits right now make a marked difference to the case rates that we have? There is a real question mark over that, she said.

The Government is hesitant to move back to red on public health grounds but also because it would risk driving the economy further towards a recession, further placing pressure on businesses already struggling with an uptick in Covid cases.

The NZIER Quarterly Survey of Business Opinion on Tuesday showed business confidence at its lowest level since the onset of the pandemic in March 2020. ANZ bank economists warned that it was not a good sign for the economy.

For broader economic momentum, it seems the only way from here is down. That is not to say the economic fundamentals have suddenly broken; rather, the economy is running out of resource to grow, they said.

The Reserve Bank of Australias decision to push up its cash rate target still leaves the Australian rate lower than New Zealands at 2%. New Zealands rate is widely expected to be pushed up to 2.5% when the Reserve Banks monetary policy committee meets next week.

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Inflation never far away as PM Jacinda Ardern heads to Sydney to sell New Zealand - Stuff

Growing Prevalence & Recurrence Of Rheumatoid Arthritis Is Expected To Growth Of The Rheumatoid Arthritis Stem Cell Therapy Market Designer Women…

The Global Rheumatoid Arthritis Stem Cell Therapy Market is replete with new growth opportunities and expansion avenues. There has been an increase in the use of products and services falling under the ambit of Rheumatoid Arthritis Stem Cell Therapy, giving a thrust to the growth of the global Rheumatoid Arthritis Stem Cell Therapy market. The unprecedented use of these products can be attributed to the increasing paying capacity of the masses.

Furthermore, in the absence of robust or utilitarian alternatives, the demand within the global Rheumatoid Arthritis Stem Cell Therapy market is projected to reach new heights of recognition. It is worthwhile to mention that the global Rheumatoid Arthritis Stem Cell Therapy market is treading along a lucrative pathway due to favorable government legislations.

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The COVID-19 pandemic has changed narratives related to growth and expansion across several key industries. Therefore, the Rheumatoid Arthritis Stem Cell Therapy market is also battling the cons of supply chain disruptions and procurement issues. Over the course of the next quarter, market players could be investing in new technologies to recover from the shocks of the pandemic.

The global market for rheumatoid arthritis stem cell therapy is highly fragmented. Examples of some of the key players operating in the global rheumatoid arthritis stem cell therapy market include Mesoblast Ltd., Roslin Cells, Regeneus Ltd, ReNeuron Group plc, International Stem Cell Corporation, TiGenix and others.

Through the latest research report on Rheumatoid Arthritis Stem Cell Therapy market, the readers get insights on:

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Tentatively, the global rheumatoid arthritis stem cell therapy market can be segmented on the basis of treatment type, application, end-user, and geography.

Based on treatment type, the global rheumatoid arthritis stem cell therapy market can be segmented into:

Based on application, the global rheumatoid arthritis stem cell therapy market can be segmented into:

Based on the distribution channel, the global rheumatoid arthritis stem cell therapy market can be segmented into:

Based on geography, the global rheumatoid arthritis stem cell therapy market can be segmented into:

The study further identifies major manufacturing trends, technologies that will be commercialized

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Growing Prevalence & Recurrence Of Rheumatoid Arthritis Is Expected To Growth Of The Rheumatoid Arthritis Stem Cell Therapy Market Designer Women...

Diabetic foot treatment: Here’s all you need to know about stem cell therapy – Hindustan Times

Diabetes is nothing less than a pandemic as according to the World Health Organization, about 422 million people have diabetes worldwide. High blood sugar levels affect different organs and tissues of the body leading to a compromised quality of life for example, you might have experienced or heard of tingling sensation, numbness, or pain in the legs/feet of patients with diabetes which as per the health experts, occur due to nerve and blood circulation-related problems caused by the negative effects of high glucose levels on cells and tissues.

Foot-related problems occur commonly in patients with diabetes like if we hurt our toe/foot and have an open wound or cut, the nerve endings from the affected part send signals to the brain and cause pain. In case a person with uncontrolled and long-standing diabetes, the sensation of pain may not be transmitted properly due to nerve issues, leading to the patient ignoring the problem and in such cases, even a small cut can progress to a large size wound (as we know wound healing is affected in diabetic patients).

Infection can spread from the feet through the blood to other parts of the body as well and in the feet specifically, increased severity of the issue can lead to gangrene, ultimately necessitating amputation of the toes/foot. It is therefore important to look out for issues such as cuts, bruises, red spots, warm areas, swelling, blisters, corn, etc. in the feet to identify any issue at the earliest and initiate treatment.

From an advanced treatment perspective, Dr Pradeep Mahajan, Regenerative Medicine Researcher at Navi Mumbai's StemRx Bioscience Solutions Pvt Ltd, talked about regenerative medicine for diabetic foot in an interview with HT Lifestyle. He explained, Regenerative medicine is about using biological molecules to enhance the healing potential of the body. These molecules are cells, growth factors, exosomes, peptides, all of which function to enhance the function of other cells in the body, reduce inflammation, regulate the immune system, provide a constant pool of healthy cells, and clear tissue damage, among other functions.

He highlighted that the treatment for diabetic foot includes a combination of mesenchymal stem cells, growth factors that improve nerve health and blood vessel formation, oxygen therapy, as well as allied stimulation-based treatments. He said, We have seen successful outcomes in diabetic foot conditions following cell-based therapy. Patients experience relief from abnormal sensations in the feet, better wound healing and pain along with better control of diabetes.

Dr Mahajan added, When we target the pathology, we get more definitive treatment outcomes. Our patients with diabetic foot do not progress to develop gangrene. In fact, they even achieve better control of blood glucose levels, which prevents further complication and improves their quality of life. The key is a regenerative (not symptomatic) treatment along with lifestyle modifications.

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Diabetic foot treatment: Here's all you need to know about stem cell therapy - Hindustan Times

Catherine S. Diefenbach, MD, Talks Future of CAR T-cell Therapy Following Liso-Cel Approval in Second-Line LBCL – Cancer Network

Catherine S. Diefenbach, MD, spoke about refining understanding of CAR T-cell therapies after the approval of lisocabtagene maraleucel for patients with relapsed/refractory large B-cell lymphoma.

Lisocabtagene maraleucel (liso-cel; Breyanzi) was recently approved for the second-line treatment of patients with relapsed/refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma not otherwise specified; high-grade B-cell lymphoma; primary mediastinal LBCL; and grade 3B follicular lymphoma.1 CancerNetwork spoke with Catherine S. Diefenbach, MD, director of both Hematology and Translational Research and the Clinical Lymphoma Program of Perlmutter Cancer Center at NYU Langone Health, about data from the phase 3 TRANSFORM trial (NCT03575351) that led to the approval and how the indication for this and other similar therapies may be expanded in the future with better understand regarding how to tailor the therapy.2

There are a couple of steps that are going to be important. One is to get a better idea of who benefits so we can tailor this therapy to the patients who are going to benefit the most. We need to get better at understanding the mechanisms of relapse and nonresponse to CAR T-cell therapy so that we [avoid subjecting] patients to this toxic therapy who are unlikely to benefit and/or design a next-generation CAR T-cell treatment that is going to allow more patients to have a durable response and be cured than what is currently approved. We need to get better at managing the toxicity of CAR T cells because this is still a fairly toxic therapy, and design next-generation CAR T cells that are less toxic. We need to get better about improving access so more patients can have access to CAR T cells. There are still many issues around insurance and payments for commercial CAR T cells. From a drug development, a clinical, and a public health standpoint, theres still much work that we can do to optimize this therapy.

This is an exciting time in lymphoma. We have a new therapy that was approved initially in the third line thats now moving to the second line and other exciting therapies that are nearing approval. We have more ways than ever to cure patients with lymphoma or extend the lives of people with incurable lymphoma. The challenge going forward is going to understand who benefits from which therapy and understand how to optimize response for all patients with these exciting therapies that we now have. This is an absolutely wonderful and transformative development.

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Catherine S. Diefenbach, MD, Talks Future of CAR T-cell Therapy Following Liso-Cel Approval in Second-Line LBCL - Cancer Network

Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study | Blood Cancer Journal…

Preclinical evaluation of FasT CAR-T cellsFasT CAR-T (F-CAR-T) proliferation in vitro

To characterize the in vitro proliferative capacity of F-CAR-T cells, F-CAR-T and C-CAR-T cells were manufactured in parallel (Supplementary Methods, and Fig. S1) using T-cells from 6 B-ALL patients. To investigate the ex vivo proliferation of F-CAR-T, frozen CD19 F-CAR-T and C-CAR-T cells from each patient were thawed and stimulated with irradiated CD19-expressing K562 cells. The number of CD19-targeting CAR-T cells was then determined during the course of cell expansion in vitro. As shown in Fig. 1A, upon CD19 antigen stimulation, F-CAR-T proliferation was much more robust compared to C-CAR-T proliferation. On day 17 post co-culture, F-CAR-T expanded 1205.61226.3 fold (MeanSD), while C-CAR-T expanded only 116.437.2 fold (MeanSD), (p=0.001). To characterize the mechanism underlying the superior proliferative ability of F-CAR-T, we purified CD19+ CAR-T cells from both F-CAR-T and C-CAR-T. The expression of genes involved in cell proliferation, cell cycle, and apoptosis was analyzed using Nanostring (detailed gene sets are in Table S2). Gene expression profiles showed higher F-CAR-T expression scores for genes associated with cell cycle regulation (F-CAR-T vs. C-CAR-T, p<0.01) and lower expression scores for apoptosis-related genes (F-CAR-T vs. C-CAR-T, p<0.05) in F-CAR-T cells (Fig. S2A).

A Ex vivo cell proliferation of F-CAR-T and C-CAR-T derived from B-ALL patients (n=6) (***P=0.001, F-CAR-T vs. C-CAR-T, d17, unpaired student two-tailed t-test). B Tscm, Tcm, and Tem were characterized by surface staining of CD45RO and CD62L and analyzed with flow cytometry (***P<0.001 comparing F-CAR-T and C-CAR-T). C T-cell exhaustion was characterized by PD-1, LAG3, and TIM-3 staining; Statistical analyses of the percentage of PD1+ LAG3+ Tim3+ (***P<0.001, comparing F-CAR-T and C-CAR-T), unpaired student two-tailed t-test). D RTCA assay was used to examine the specific killing of HeLa-CD19 cells. Growth of target HeLa-CD19 or HeLa cells were monitored dynamically. E CD19+ target Nalm6-Luc cells or F Raji-Luc cells were co-cultured with either F-CAR-T or C-CAR-T for 6h. Target cell killing efficacy was calculated by luciferase activity. NS, P>0.05 F-CAR-T vs. C-CAR-T (unpaired student t-test, two-tailed). F-CAR-T FasT CAR-T, C-CAR-T conventional CAR-T, Tcm (CD45RO+CD62L+) T central memory cells, Tem (CD45RO+CD62L) T effector memory cells, Tscm (CD45ROCD62L+) T stem cell memory, PD1 programmed cell death protein 1, TIM-3 T cell immunoglobulin and mucin domain containing-3, LAG3 lymphocyte-activation gene 3, RTCA real-time cell analyzer, E:T effector cells: target cells, NT normal T-cell.

Phenotypes of unstimulated F-CAR-T from three healthy donors were analyzed by flow cytometry. The CD45ROCD62L+ population was 45.7%2.2% which was comparable to the un-transduced T-cells (data not shown). Upon stimulation with CD19+ tumor cells for 9 days, C-CAR-T central memory cells (Tcm, CD45RO+CD62L+ and effector memory cells (Tem, CD45RO+CD62L) were 56.62%11.97% and 40.48%9.70%, respectively, among the C-CAR-T cells (Fig. 1B and Figs. S2B and S2). In contrast, Tcm cells (87.92%4.36%) was predominant in F-CAR-T, with only a small fraction of Tem (7.84%3.79%). In addition, F-CAR-T cells demonstrated more abundant T stem cell memory (Tscm) (3.841.22% vs 2.342.48%, p<0.05) than C-CAR-T cells. We also examined the exhaustion status of the stimulated CAR-T cells. A higher percentage of PD-1+LAG3+Tim3+T-cells were detected in the C-CAR-T (11.19%2.54%) compared to F-CAR-T (3.59%2.51%, p<0.001) (Fig. 1C). Together these data indicated that the F-CAR-T exhibited a younger phenotype and was less exhausted compared to C-CAR-T.

We used a real-time cell analyzer (RTCA) assay to measure the cytotoxicity of F-CAR-T and C-CAR-T against CD19+ cells in vitro. F-CAR-T and C-CAR-T killing of Hela-CD19 target cells were comparable using this assay (Fig. 1D). Similar levels of IFN- and IL-2 production were also observed (Fig. S2D). In a luciferase-based cytotoxicity assay, CD19+ B leukemia cell lines, Raji and Nalm6, were both effectively killed to similar or better levels at different E:T ratios (Fig. 1E, F).

To compare the in vivo cytotoxicity of F-CAR-T and C-CAR-T, severe immunodeficient NOG mice were engrafted with Raji-luciferase cells. One week after the tumor grafts were established, F-CAR-T and C-CAR-T were intravenously injected at various doses. The engrafted tumors progressed aggressively in control groups with either vehicle alone or control T-cells (Fig. 2A). In contrast, F-CAR-T or C-CAR-T treatment greatly suppressed tumor growth in a dose-dependent manner (Fig. 2A). In the high dose group (2106/mice), both F-CAR-T and C-CAR-T eliminated the tumor rapidly. However, in the low dose group (5105/mice), F-CAR-T showed more effective tumor-killing compared to C-CAR-T. On day 20, mice in the low dose F-CAR-T group became tumor-free, while C-CAR-T treated mice exhibited tumor relapse (Fig. 2A). We examined the CAR-T cell expansion in vivo after infusion. As shown in Fig. 2B, both F-CAR-T and C-CAR-T began to expand in the peripheral blood 7 days after infusion. C-CAR-T cell numbers reached their peak on day 14 and receded on day 21. In contrast, the F-CAR-T cell number peaked on day 21 and declined to a baseline level on day 28. F-CAR-T not only persisted longer but also underwent 26 folds greater expansion than C-CAR-T (Fig. 2B).

A Raji-Luc cell engraftment NOG mice were given high dose (2106/mice, n=3) and low dose (5105/mice, n=3) F-CAR-T/C-CAR-T along with control groups. Tumor growth was monitored with IVIS scan once every 3 days; B CAR-T expansion in peripheral blood of mice was analyzed by flow cytometry (n=6). ***P<0.001 for F-CAR-T HD vs. C-CAR-T HD; F-CAR-T LD vs. C-CAR-T LD; F-CAR-T HD vs. F-CAR-T LD; C-CAR-T HD vs. C-CAR-T LD (two-way ANOVA statistical analysis); C Schematic of the Nalm6 (1106) xenograft model, CAR-T (2106) infused 1 day after cyclophosphamide (20mg/kg) treatment. Bone marrow infiltration of F-CAR-T was analyzed 10 days after CAR-T infusion (n=3); D CD45+CD2 F-CAR-T vs. C-CAR-T in peripheral blood of mice were analyzed by flow cytometry; *P<0.05 (unpaired student two-tailed t-test). IVIS in vivo imaging system, PB peripheral blood, i.v. intravenous, HD high dose, LD low dose, Cy cyclophosphamide; *p<0.05; #: number.

We examined the BM infiltration of F-CAR-T cells after infusion into Nalm6-bearing mice (Fig. 2C). A larger population of CAR-T cells was observed 10 days after infusion in BM in F-CAR-T infused group than that in the C-CAR-T group (p<0.05) (Fig. 2D), suggesting F-CAR-T cells possessed a better BM homing capability than C-CAR-T.

The chemokine receptor CXCR4 is known to be critical for BM homing of T-cells [25, 26]. Indeed, a higher percentage of CXCR4+ T cells were detected in F-CAR-T than in the C-CAR-T. Interestingly, this phenotype was more pronounced for CD4+ T cells than CD8+ T cells (Fig. S3A). In a two-chamber system, more F-CAR-T cells could be detected in the lower chamber than their C-CAR-T counterparts (Fig. S3B).

Between Jan. 2019 and Oct. 2019, 25 pediatric and adult patients with CD19+R/R B-ALL were enrolled onto our phase 1 trial, including two patients who had relapsed following a prior allo-HSCT. Patient characteristics are detailed in Table 1. The median age of patients was 20 (range: 344) years old. Twenty patients were >14 years old, and five were 14 years old. The median percentage of pre-treatment BM blasts was 9.05% (range: 0.1982.9%). As our pre-clinical studies demonstrated that F-CAR-T cells had a superior expansion capability as compared to C-CAR-T, we infused a relatively low doses of F-CAR-T cells, ranging from 104105 cells/kg: 3.0104 cells/kg (n=2), 6.5 (5.867.43)104 cells/kg (n=9), 1.01 (1.01.16)105 cells/kg (n=12), 1.52(1.471.56)105 cells/kg (n=2), (Fig. S4). The median time from apheresis to the infusion of CD19+F-CAR-T cells was 14 days (range: 1220). Although the manufacturing time of F-CAR-T was next day, the quality control time and detailed final product releases including sterility testing require a minimum of 710 days to complete. In addition, transportation of cell products requires approximately two days. Of the 25 patients who received CD19 F-CAR-T infusion, 22 (88%) received bridging chemotherapy between apheresis and lymphodepleting chemotherapy to control rapid disease progression (Table S3).

F-CAR-T cells were manufactured successfully for all patients. The mean transduction efficiency of F-CAR-T was 35.4% (range: 13.170.3%) (Fig. S5A). Both CD4+/CAR+ (mean, 49.6%; range: 13.673.2%) and CD8+/CAR+ (mean, 41.5%; range: 20.677.7%) subsets were present in the CD3+CAR+ T cell subsets of all products. The mean proportion of Tscm, Tem, and Tcm cells in the CD3+CAR+ T cell subsets of all products was 23.3% (range: 3.5545.3%), 33.2% (range: 17.267.9%), and 36.1% (range: 20.758.1%), respectively (Fig. S5B). F-CAR-T products exerted significant IFN- release and cytotoxic effects against the CD19+ cell line HELA-CD19 (Fig. S5, C, D).

All 25 infused patients experienced adverse events (AEs) of any grade, with 25 (100%) experiencing grade 3 or higher adverse events. No grade 5 events related to F-CAR-T treatment were observed (Table 2).

CRS occurred in 24 (96%) patients with 18 (72%) grade 12 CRS,6 (24%) of grade 3, and no grade 4 or higher CRS (Fig. S6). In the >14 years old group, 16/20 (80%) patients developed mild CRS, and only 2/20 (10%) developed grade 3 CRS. For 14 years old patients, 2/5 (40%) had mild CRS, yet 3/5 (60%) experienced grade 3 CRS (Table S4). ICANS was observed in 7 (28%) patients, with 2 (8%) grade 3 ICANS occurring in patients >14 years old and 5 (20%) grade 4 ICANS all occurring in patients 14 years old. No grade 5 ICANS was developed (Fig. S7 and Table S4). The most frequent presentation of CRS was fever, particularly a high fever of >39C. The first onset of CRS symptoms occurred between day 3 and 8 post-CAR-T infusion with a median onset at day 4 (range: 110 days). The most common symptoms of ICANS were seizure (5/7) and depressed consciousness (5/7). The median time to ICANS onset from CAR-T cell infusion was 7 days (range: 58), and the median time to resolution was 2 days (Fig. S7). All CRS and ICANS events were managed including early intervention when fever of 39C persisted for 24h. Sixteen (64%) patients received tocilizumab with a median total dose of 160mg (range: 160320mg). Twenty-one (84%) patients received corticosteroids including dexamethasone (median total dose, 43mg; range: 4127mg) and or methylprednisolone (median total dose, 190mg; range: 401070mg). The vast majority of these patients discontinued corticosteroids within 2 weeks. The change in IL-6, IFN-, IL-10, and GM-CSF levels after infusion are selectively shown in Fig. S8. The peak levels of these four cytokines were observed between day 710. Among all 21 cytokines examined, only post-infusion IL-6 levels were associated with moderate to severe CRS and/or ICANS (Figs. S9 and S10).

Superior in vivo proliferation and persistence of F-CAR-T compared to C-CAR-T cells were observed regardless of dose levels. The median peak level was reached on day 10 (range: 714 days) with 1.9105 transgene copies/g of genomic DNA (range: 0.225.2105 transgene copies/g of genomic DNA) by qPCR and 83 F-CAR-T cells per l blood (range: 42102 F-CAR-T cells per l blood) by FCM (Fig. 3A, B). No significant differences were observed among the different dose groups in the mean F-CAR-T copies peak (Fig. 3C). Importantly, there was no significant difference in the mean F-CAR-T copies peak between patients who received corticosteroids compared to those who did not (Fig. 3D).

A F-CAR-T cells in peripheral blood by qPCR. Purple, dose level 1; black, dose level 2; blue, dose level 3; red, dose level 4; B F-CAR-T cells in peripheral blood by flow cytometry. Purple, dose level 1; black, dose level 2; blue, dose level 3; red, dose level 4; C Comparison of the mean peak copy number of F-CAR-T cells in peripheral blood at each dose level. Statistical significance was determined by the MannWhitney test. D Comparison of the mean peak copy number of F-CAR-T cells in peripheral blood with or without steroids. Statistical significance was determined by the MannWhitney test.

Fourteen days after F-CAR-T cell infusion, all patients achieved morphologic CR including 2/25 with CR and 23/25 CR with incomplete hematologic recovery (CRi), which further improved to 11/25 CR and 14/25 CRi 28 days post F-CAR-T (Table 1 and Fig. 4). More importantly, 23/25 (92%) had the minimal residual disease (MRD)-negative remission on day 14 and day 28 after F-CAR-T treatment. Patients achieving remission through CAR-T were given the option to proceed to allo-HSCT. With a median time of 54 days (range: 4581 days) post F-CAR-T infusion, 20 of 23 patients with MRD-negative status decided to pursue consolidative allo-HSCT including one patient who received a 2nd transplant. As of 18 October 2021, with a median follow-up duration of 693 days (range: 84973 days) among the 20 patients who had received allo-HSCT, one patient relapsed on day 172 and died 3 months after relapse, and four patients died from transplant-related mortality (TRM) including infection (n=3) and chronic GVHD (n=1) on day 84, day 215, day 220, and day 312, respectively. The other 15 patients remained in MRD-negative CR with a median remission duration of 734 days (range: 208973) except for one who became MRD-positive on day 294 with CD19+ disease. Among the other three patients (F05, F06, F16), one remained in MRD-negative CR on day 304, one remained in MRD-negative CR until day 303, received allo-HSCT but died from an infection on day 505, and one was lost to follow-up after day 114. Two patients who had MRD-positive CR after infusion withdrew from the study on day 42 and day 44, respectively, to seek other studies.

Clinical outcomes and consolidative allo-HSCT for the 25 patients who were treated with F-CAR-T therapy are shown. On day 28, 23/25 patients achieved MRD-negative CR/CRi. With a median time of 54 days (range: 4581) post F-CAR-T infusion, 20 of 23 patients with MRD-negative status received consolidative allo-HSCT. Among the 20 patients, 1 patient (F23) relapsed on day 172 and died 3 months after relapse. Four patients (F04, F09, F11, F12) died from transplant-related mortality (TRM) including infection (n=3) and chronic GVHD (n=1) on day 84, day 215, day 220, and day 312, respectively. The remaining 15 patients were in MRD-negative CR except for one (F18) who became MRD-positive on day 294. Among the other 3 patients (F05, F06, F16), 1 remained MRD-negative CR on day 304, 1 remained in MRD-negative CR until day 303, received allo-HSCT, and subsequently died from an infection on day 505. One patient was lost to follow-up after day 114. MRD minimal residual disease, CR complete remission, Allo-HSCT allogeneic hematopoietic stem cell transplantation.

F-CAR-T/T ratio in cerebrospinal fluid (CSF) was evaluated by FCM in 13/25 patients with available samples (Table S5). Between days 10 and 32, 9 patients were found to have considerable F-CAR-T penetration in their CSF, ranging from 40.65 to 79.2%, including 4 who developed severe ICANS. Among the other 4 patients, F-CAR-T cell abundance in the CSF ranged from 1.29% to 3.57%, and none experienced severe ICANS. Patients with higher levels of CAR-T in PB on day 10 consistently had higher levels of CAR-T in CSF with the exception of patient F15. Notably, CAR-T cells were still detectable in the CSF on day 101 with a 2.36% CAR-T/T ratio in patient F06, who also had undetectable circulating CAR-T cells at the same time.

In addition, concentrations of seven cytokines (IL-1b, IL-6, IL-10, IFN-, TNF-, MCP-1, and GM-CSF) in CSF samples from the above 10 of 13 patients were measured. Specifically, IL-1b was not detected in any of the 10 patients, and only one patient had detectable GM-CSF. For the other five cytokines, patients with severe ICANS had higher IL-6 levels in contrast to patients without severe ICANS, and the difference between the median level of IL-6 among these two groups of patients was statistically significant (Fig. S11). We did not observe significant differences among the other 4 cytokines between the two groups of patients. No clear relation between the CSF cytokine levels and the F-CAR-T/T % was observed.

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Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study | Blood Cancer Journal...

Jasper Therapeutics to Participate in the William Blair 42nd Annual Growth Stock Conference – GuruFocus.com

REDWOOD CITY, Calif., June 07, 2022 (GLOBE NEWSWIRE) -- Jasper Therapeutics, Inc. ( JSPR), a biotechnology company focused on enabling cures with stem cell therapies, today announced that the Company is participating in the William Blair 42nd Annual Growth Stock Conference, to be held in Chicago from June 6-9, 2022.

Ronald Martell, Jaspers Chief Executive Officer, is scheduled to present on Thursday, June 9th at 8:00AM CT, with a breakout session to follow at 8:40AM CT. A live webcast of the presentation will be available at https://wsw.com/webcast/blair66/jasp/1933236 and at the Companys Investor Events webpage.

About Jasper TherapeuticsJasper Therapeutics, Inc. is a biotechnology company focused on the development of novel curative therapies based on the biology of the hematopoietic stem cell. The company is advancing two potentially groundbreaking programs. JSP191, an anti-CD117 monoclonal antibody, is in clinical development as a conditioning agent that clears hematopoietic stem cells from bone marrow in patients undergoing hematopoietic cell transplantation. It is designed to enable safer and more effective, and potentially curative, allogeneic hematopoietic cell transplants and gene therapies. A clinical study of JSP191 as a novel, disease-modifying, therapeutic for patients with lower risk MDS is also planned to begin in 2022. In parallel, Jasper Therapeutics, Inc. is advancing its preclinical mRNA hematopoietic stem cell grafts platform, which is designed to overcome key limitations of allogeneic and autologous gene-edited stem cell grafts. Both innovative programs have the potential to transform the field and expand hematopoietic stem cell therapy cures to a greater number of patients with life-threatening cancers, genetic diseases and autoimmune diseases than is possible today. For more information, please visit us at jaspertherapeutics.com.

Forward-Looking StatementsCertain statements included in this press release that are not historical facts are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements are sometimes accompanied by words such as believe, may, will, estimate, continue, anticipate, intend, expect, should, would, plan, predict, potential, seem, seek, future, outlook and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, statements regarding the potential of the Companys JSP191 and mRNA engineered stem cell graft programs. These statements are based on various assumptions, whether or not identified in this press release, and on the current expectations of Jasper and are not predictions of actual performance. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as, and must not be relied on by an investor as, a guarantee, an assurance, a prediction or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and will differ from assumptions. Many actual events and circumstances are beyond the control of Jasper. These forward-looking statements are subject to a number of risks and uncertainties, including general economic, political and business conditions; the risk that the potential product candidates that Jasper develops may not progress through clinical development or receive required regulatory approvals within expected timelines or at all; risks relating to uncertainty regarding the regulatory pathway for Jaspers product candidates; the risk that prior study results may not be replicated; the risk that clinical trials may not confirm any safety, potency or other product characteristics described or assumed in this press release; the risk that Jasper will be unable to successfully market or gain market acceptance of its product candidates; the risk that Jaspers product candidates may not be beneficial to patients or successfully commercialized; patients willingness to try new therapies and the willingness of physicians to prescribe these therapies; the effects of competition on Jaspers business; the risk that third parties on which Jasper depends for laboratory, clinical development, manufacturing and other critical services will fail to perform satisfactorily; the risk that Jaspers business, operations, clinical development plans and timelines, and supply chain could be adversely affected by the effects of health epidemics, including the ongoing COVID-19 pandemic; the risk that Jasper will be unable to obtain and maintain sufficient intellectual property protection for its investigational products or will infringe the intellectual property protection of others; and other risks and uncertainties indicated from time to time in Jaspers filings with the SEC. If any of these risks materialize or Jaspers assumptions prove incorrect, actual results could differ materially from the results implied by these forward-looking statements. While Jasper may elect to update these forward-looking statements at some point in the future, Jasper specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Jaspers assessments of any date subsequent to the date of this press release. Accordingly, undue reliance should not be placed upon the forward-looking statements.

Contacts:

John Mullaly (investors)LifeSci Advisors617-429-3548[emailprotected]

Jeet Mahal (investors)Jasper Therapeutics650-549-1403[emailprotected]

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Jasper Therapeutics to Participate in the William Blair 42nd Annual Growth Stock Conference - GuruFocus.com