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Respiratory Care




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The antivirulent Staphylococcal sRNA SprC regulates CzrB efflux pump to adapt its response to zinc toxicity [ARTICLE]

Bacterial regulatory RNAs (sRNAs) are important players to control gene expression. In Staphylococcus aureus, SprC is an antivirulent trans-acting sRNA known to base-pair with the major autolysin atl mRNA, preventing its translation. Using MS2-affinity purification coupled with RNA sequencing, we looked for its sRNA-RNA interactome and identified 14 novel mRNA targets. In vitro biochemical investigations revealed that SprC binds two of them, czrB and deoD, and uses a single accessible region to regulate its targets, including Atl translation. Unlike Atl regulation, the characterization of the SprC-czrB interaction pinpointed a destabilization of the czrAB cotranscript, leading to a decrease of the mRNA level that impaired CzrB zinc efflux pump expression. On a physiological standpoint, we showed that SprC expression is detrimental to combat against zinc toxicity. In addition, phagocyctosis assays revealed a significant, but moderate, increase of czrB mRNA levels in a sprC-deleted mutant, indicating a functional link between SprC and czrB upon internalization in macrophages, and suggesting a role in resistance to both oxidative and zinc bursts. Altogether, our data uncover a novel pathway in which SprC is implicated, highlighting the multiple strategies used by S. aureus to balance virulence using an RNA regulator.




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Ensuring availability of respiratory medicines in times of European drug shortages

Extract

It is of utmost importance that medicines are available at all times for our patients. Historically, medication unavailability has typically, if not exclusively, affected low- and middle-income countries [1]. More recently however, drug shortages have also been reported in high-income European countries [2]. Drug shortages have negative health consequences for patients [3], and a profound economic impact, with the need to resort to more expensive alternatives and demands on healthcare professionals’ time to find, prescribe and dispense alternatives [4].




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Delays in Cardiovascular Emergency Responses in Africa: Health System Failures or Cultural Challenges?




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[18F]AlF-NOTA-FAPI-04 PET/CT for Predicting Pathologic Response of Resectable Esophageal Squamous Cell Carcinoma to Neoadjuvant Camrelizumab and Chemotherapy: A Phase II Clinical Trial

This single-center, single-arm, phase II trial (ChiCTR2100050057) investigated the ability of 18F-labeled fibroblast activation protein inhibitor ([18F]AlF-NOTA-FAPI-04, denoted as 18F-FAPI) PET/CT to predict the response to neoadjuvant camrelizumab plus chemotherapy (nCC) in locally advanced esophageal squamous cell carcinoma (LA-ESCC). Methods: This study included 32 newly diagnosed LA-ESCC participants who underwent 18F-FAPI PET/CT at baseline, of whom 23 also underwent scanning after 2 cycles of nCC. The participants underwent surgery after 2 cycles of nCC. Recorded PET parameters included maximum, peak, and mean SUVs and tumor-to-background ratios (TBRs), metabolic tumor volume, and total lesion FAP expression. PET parameters were compared between patient groups with good and poor pathologic responses, and the predictive performance for treatment response was analyzed. Results: The good and poor response groups each included 16 participants (16/32, 50.0%). On 18F-FAPI PET/CT, the posttreatment SUVs were significantly lower in good responders than in poor responders, whereas the changes in SUVs with treatment were significantly higher (all P < 0.05). SUVmax (area under the curve [AUC], 0.87; P = 0.0026), SUVpeak (AUC, 0.89; P = 0.0017), SUVmean (AUC, 0.88; P = 0.0021), TBRmax (AUC, 0.86; P = 0.0031), and TBRmean (AUC, 0.88; P = 0.0021) after nCC were significant predictors of pathologic response to nCC, with sensitivities of 63.64%–81.82% and specificities of 83.33%–100%. Changes in SUVmax (AUC, 0.81; P = 0.0116), SUVpeak (AUC, 0.82; P = 0.0097), SUVmean (AUC, 0.81; P = 0.0116), and TBRmean (AUC, 0.74; P = 0.0489) also were significant predictors of the pathologic response to nCC, with sensitivities and specificities in similar ranges. Conclusion: 18F-FAPI PET/CT parameters after treatment and their changes from baseline can predict the pathologic response to nCC in LA-ESCC participants.




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Granzyme B PET/CT Imaging Evaluates Early Response to Immunotherapy in Gastric Cancer

In several malignancies, only a limited number of patients respond to immune checkpoint inhibitors. Predicting and monitoring responses to these inhibitors represent an unmet clinical need. Here, we developed a PET/CT probe targeting granzyme B, [68Ga]Ga-NOTA-Gly-Gly-Gly-Ile-Glu-Pro-Asp-CHO (GSI), and aimed to investigate whether it can be used to monitor the effects of immune checkpoint inhibitors early in the course of therapy. Methods: Seventy-two patients with gastric cancer (stages III–IV) were recruited for [68Ga]Ga-NOTA-GSI PET/CT imaging after 2 or 3 cycles of the immunotherapy, and 40 patients were included in the final analysis. The SUVmax of primary tumors (SUVmax-t), SUVmax of metastatic lymph nodes (SUVmax-LN), and SUVmax of normal tissues (liver and blood pool) were measured, and their target-to-liver background ratio (TLR) and target-to-blood background ratio (TBR) were denoted for primary tumors as TLRtumor and TBRtumor and for metastatic lymph nodes as TLRLN and TBRLN, respectively. The treatment responses were assessed within 1 wk after full-course treatment according to RECIST version 1.1. Wilcoxon rank-sum tests were used to compare the PET/CT parameters between responders and nonresponders. Receiver operating characteristic curve analysis was used to assess the diagnostic efficacy of [68Ga]Ga-NOTA-GSI PET/CT parameters in identifying responders. Two-tailed P value of less than 0.05 was considered statistically significant. Results: We found that SUVmax-t, TLRtumor, TBRtumor, SUVmax-LN, and TBRLN were higher in responders than in nonresponders (2.49 ± 0.58 vs. 1.55 ± 0.48, P = 0.000; 2.24 ± 0.48 vs. 1.74 ± 0.67, P = 0.007; 1.38 ± 0.43 vs. 0.90 ± 0.23, P = 0.000; 2.24 ± 0.99 vs. 1.42 ± 0.55, P = 0.003; and 1.28 ± 0.68 vs. 0.83 ± 0.32, P = 0.012, respectively). According to receiver operating characteristic curve analysis, the area under the curve for SUVmax-t, TBRtumor, TLRtumor, SUVmax-LN, TLRLN, and TBRLN was 0.886, 0.866, 0.746, 0.772, 0.648, and 0.731, respectively. The threshold of SUVmax-t was 2.05, and its sensitivity and specificity were 81.0% and 84.2%, respectively. In addition, multivariate logistic regression indicated that TBRtumor was an independent predictor of treatment response (P = 0.03). Conclusion: Our results indicated that [68Ga]Ga-NOTA-GSI PET/CT is a promising tool for predicting early response to combined immunotherapy in gastric cancer patients.




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Pazopanib elicits remarkable response in metastatic porocarcinoma: a functional precision medicine approach [RESEARCH REPORT]

Metastatic porocarcinomas (PCs) are vanishingly rare, highly aggressive skin adnexal tumors with mortality rates exceeding 70%. Their rarity has precluded the understanding of their disease pathogenesis, let alone the conduct of clinical trials to evaluate treatment strategies. There are no effective agents for unresectable PCs. Here, we successfully demonstrate how functional precision medicine was implemented in the clinic for a metastatic PC with no known systemic treatment options. Comprehensive genomic profiling of the tumor specimen did not yield any actionable genomic aberrations. However, ex vivo drug testing predicted pazopanib efficacy, and indeed, administration of pazopanib elicited remarkable clinicoradiological response. Pazopanib and its class of drugs should be evaluated for efficacy in other cases of PC, and the rationale for efficacy should be determined when PC tumor models become available. A functional precision medicine approach could be useful to derive effective treatment options for rare cancers.




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Rapid genome diagnosis of alveolar capillary dysplasia leading to treatment in a child with respiratory and cardiac failure [RESEARCH REPORT]

Alveolar capillary dysplasia (ACD) is a fatal disorder that typically presents in the neonatal period with refractory hypoxemia and pulmonary hypertension. Lung biopsy is traditionally required to establish the diagnosis. We report a 22-mo-old male who presented with anemia, severe pulmonary hypertension, and right heart failure. He had a complicated hospital course resulting in cardiac arrest and requirement for extracorporeal membrane oxygenation. Computed tomography of the chest showed a heterogenous pattern of interlobular septal thickening and pulmonary edema. The etiology of his condition was unknown, lung biopsy was contraindicated because of his medical fragility, and discussions were held to move to palliative care. Rapid whole-genome sequencing (rWGS) was performed. In 2 d it resulted, revealing a novel FOXF1 gene pathogenic variant that led to the presumptive diagnosis of atypical ACD. Cases of atypical ACD have been reported with survival in patients using medical therapy or lung transplantation. Based on the rWGS diagnosis and more favorable potential of atypical ACD, aggressive medical treatment was pursued. The patient was discharged home after 67 d in the hospital; he is currently doing well more than 30 mo after his initial presentation with only one subsequent hospitalization and no requirement for lung transplantation. Our case reveals the potential for use of rWGS in a critically ill child in which the diagnosis is unknown. rWGS and other advanced genetic tests can guide clinical management and expand our understanding of atypical ACD and other conditions.




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Highlights from the Respiratory Failure and Mechanical Ventilation Conference 2024

The Respiratory Intensive Care Assembly of the European Respiratory Society gathered in Berlin to organise the third Respiratory Failure and Mechanical Ventilation Conference in February 2024. The conference covered key points of acute and chronic respiratory failure in adults. During the 3-day conference ventilatory strategies, patient selection, diagnostic approaches, treatment and health-related quality of life topics were addressed by a panel of international experts. In this article, lectures delivered during the event have been summarised by early career members of the Assembly and take-home messages highlighted.




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An elderly woman with acute respiratory failure and diffuse pulmonary changes




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Large-scale education in respiratory medicine: content versus delivery

The respiratory literature, both written and in online formats, is growing exponentially. Capturing quality content, to meet the learning needs of those working in all fields of respiratory medicine and delivering it in a palatable, accessible format is challenging but paramount. In this article we discuss ways to determine the information content and review different methods of delivering this content to those who need it.




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Mitch McConnell Called Donald Trump a ‘Stupid’ and ‘Despicable Human Being’

Saul Loeb, Mandel Ngan/AFP/Getty

Senate Minority Leader Mitch McConnell called his party’s presidential nominee, Donald Trump, a “stupid,” “ill-tempered,” and “despicable human being,” according to his own records.

McConnell made the withering assessments in a series of private “personal oral histories” that he gave to Michael Tackett, the deputy Washington bureau chief of the Associated Press, who has a forthcoming biography about the Kentucky senator called The Price of Power. The AP conveniently reported the book’s juicy details.

McConnell’s remarks were made after the 2020 election that Trump lost, and the senator was apparently elated to see the backside of the former president, musing, “it’s not just the Democrats who are counting the days” until he leaves office.

Read more at The Daily Beast.




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Respawn have killed Apex Legends' Steam Deck support in the name of anti-cheat

The Steam Deck is something of a talisman for gaming on Linux, its popularity and penguin-powered SteamOS having almost singlehandedly dragged it past MacOS as the second-most-used operating system among Steam users. Sadly, this also means the Valve handheld is the primary casualty when developers decide to stop bothering with Linux support, as Respawn Entertainment have decided to do for Apex Legends.

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California wine country tries to get back to business despite wildfire destruction

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JUDY WOODRUFF: Firefighters say they are making some progress battling the wildfires in Northern California. In all, the fires have consumed more than 220,000 acres, an area larger than New York City.

More than 5,700 structures have been destroyed. And at least 41 people have died, making it the deadliest wildfire in the state’s history.

The wine industry and the tourism business connected with it are trying to take stock. More than $50 billion in California’s economy comes from the wine business. And nearly 24 million people visit the region for that reason every year.

Special correspondent Joanne Jennings reports from Napa County.

JOANNE JENNINGS, Special Correspondent: The Mayacamas mountain range creates a natural barrier between Sonoma and Napa Counties. And it is here where the massive Nuns fire is posing a tough challenge for some 11,000 firefighters who are taming the blaze with aircraft and units on the ground.

CAPT. MARK BRENNERMAN, Viejas fire Department: We’re going around and making sure none of these fires that are still smoldering and smoking, we’re not going to get another big fire out of them.

JOANNE JENNINGS: Even as firefighters are battling shifting winds, owners and workers in Wine Country are trying to determine just how much damage has been done.

The tony Highlands gated community was among the first to be consumed by flames when the Atlas fire raced through this canyon, leaving several mansions in rubble. Down the hill, at the Silverado resort, charred remnants of the Safeway PGA Tour remain. The major golf event had just wrapped up last Sunday afternoon, a few hours before flames engulfed tents and grandstands, forcing spectators and athletes to evacuate.

MAN: Do you see how it burned right up to the retaining wall here?

JOANNE JENNINGS: Silverado resident Steve Messina stayed behind and shot video of fire crews containing the flames, which consumed some condos. Within minutes, flames raced three miles down Silverado Trail, home to several storied hillside vineyards.

Most wineries in the region have been spared the worst. But hundreds suffered some damage. And at least eight vineyards have been significantly damaged or destroyed.

Pierre Birebent, who has been making wines for the family-owned Signorello estate for 20 years, rushed to his winery as quickly as he could.

PIERRE BIREBENT, Signorello Estate Vineyards: I jumped right in my truck, came down, and then when I was riding down, I saw the hill all flaming.

JOANNE JENNINGS: Two vineyard workers joined him to help save the estate’s tasting room.

PIERRE BIREBENT: But the smoke was getting very thick, and the wind was very strong. And after an hour, we couldn’t breathe anymore. At the moment, I was so upset. It was rage to see that I couldn’t do anything. But it was like fighting a giant.

JOANNE JENNINGS: The tasting room, which also housed the winery’s office and a dining room, burned to the ground. But Birebent says he wants to focused on what survived.

Fortunately, he said, the fire stopped short of reaching the vineyard, the crush pad, or any of the barrels of wine stored on site; 95 percent of this year’s grapes were already picked.

But, to be on the safe side, Birebent is taking these samples to a lab to make sure the juice is not too acidic for winemaking. If the crops are OK, a staff of 25 employees will have jobs to return to.

As the fires begin to recede and the smoke clears, people here are beginning to wonder when the tourists, who fuel much of the economy, will return.

It’s a serious concern for Andrew and Jeni (ph) Schluter, who are self-employed and are raising a young family.

ANDREW SCHLUTER, Andrew’s Tours and Transportation: I do wine tours and transportation for people. And my business started to do really, really well. I was on track to have the best month ever.

JOANNE JENNINGS: Andrew just bought this new SUV, which has been idle in his driveway collecting ash. Jeni is a personal trainer and has family who lost their homes in the fires. She’s just not sure how they’re going to make ends meet.

WOMAN: I think we’re just overwhelmed, you know? And uncertainty is kind of scary.

ANDREW SCHLUTER: We will hopefully get by for awhile, but we might make — have to make some hard decisions shortly.

JOANNE JENNINGS: While fires burn nearby, some vineyards are already open to tourists. At the Raymond Vineyard, workers are crushing grapes at a feverish pitch. The tasting room is open for the first time since the fires started.

Jeremy and Erika Moore arrived from Tennessee yesterday. They considered canceling their trip, but decided the best way they could help people here is to give them their business.

JEREMY MOORE, Tourist: On the one hand, a few hundred yards from here, you can see them shuttling up with the helicopters fighting fires, but then here it’s beautiful. They are doing some great tastings, and they are working outside on the crops. So, it’s a weird combination of tragedy, but then at the same time business must go on, too.

JOANNE JENNINGS: Proprietor Jean-Charles Boisset owns several wineries in California, France and Canada, but like many other people here, he and his family had to evacuate their home when the flames came dangerously close.

Still, he is bullish about the future of the wine industry in this region.

JEAN-CHARLES BOISSET, Boisset Collection: Napa has been one of the most amazing agricultural places in California for a long time, so it will survive those fires. What I love, as a Frenchman here in California, is that amazing American positive attitude.

We will recover. We will walk again, run again, and we will welcome all our guests and give them the dreams of fine wine.

JOANNE JENNINGS: For the PBS NewsHour, I’m Joanne Jennings in Napa Valley, California.

The post California wine country tries to get back to business despite wildfire destruction appeared first on PBS NewsHour.




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As survivors say #MeToo, what will it take to stop widespread sexual harassment?

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JUDY WOODRUFF: The hashtag #MeToo has millions of women sharing stories of abuse, shining a spotlight on a troubling reality in our society.

It was first used in 2007, but when actor Alyssa Milano tweeted it Sunday night to talk about sexual harassment and assault in the wake of the Harvey Weinstein story, it went viral. The hashtag was tweeted nearly a million times in just 48 hours. Facebook reported 45 percent of its users have friends who posted #MeToo, as women wrote about their experiences about the workplace and culture, and what should change.

We explore some of those issues with Fatima Goss Graves. She’s president of the National Women’s Law Center. Lisa Senecal wrote about her own experience for the online news site Daily Beast. She’s with the Vermont Commission on Women. And Melissa Silverstein is the founder of the blog and Web site Women and Hollywood.

Thank you all for joining us.

Lisa Senecal, I’m going to start with you.

You have had a personal experience with sexual harassment. That’s in part what has drawn you to this #MeToo campaign movement.

Just tell us briefly about what happened.

LISA SENECAL, Member, Vermont Commission on Women: Sure.

Like most women, I have had a number of experiences with sexual harassment, beginning with my first job, when I was 15 years old. And it’s really been a threat off and on throughout my entire professional career.

The most egregious offense was an actual assault that occurred with a male executive. Unfortunately, because of an NDA — and we can go into the evils of nondisclosures another time — but because of that, there isn’t a lot that I’m able to say about the specific event.

But the issue of sexual harassment and finally having this come to the fore, so many women are already familiar with it from being on the receiving end. And I think, especially with the #MeToo campaign, it’s been really wonderful and an eye-opening experience for men to realize just how pervasive an issue this is.

JUDY WOODRUFF: So, in your experience, it was a business setting.

Melissa Silverstein, you have been writing about women in Hollywood for 10 years. Of course, that’s where the Harvey Weinstein story came from.

If it’s been going on in Hollywood forever, why hasn’t it been talked about more before now?

MELISSA SILVERSTEIN, Founder, Women and Hollywood: Well, I think there was a culture of silence created around this man and also within this industry.

People were afraid. People are afraid for their jobs. It’s a very relational industry, where if someone is going to blacklist you, you are not going to get your next job.

So I think the way that a person was able to conduct himself for 30 years like this was to build a culture of fear, to make people sign nondisclosure agreements, and to get them to shut up.

JUDY WOODRUFF: Fatima Goss Graves, here with me in Washington with the National Women’s Law Center, we have been talking about Hollywood.

We have talking about the business workplace. Is there any field of work where this isn’t going on?

FATIMA GOSS GRAVES, President, National Women’s Law Center: Right.

The issue of harassment and assault, it’s a Hollywood problem, but really it’s an everywhere problem. It infects industries across the board, whether you’re high-wage jobs, low-wage jobs, male-dominated fields, but also female-dominated fields.

Restaurants are some of the areas where you have some of the highest rates of EEOC charges. And that’s not a male-dominated field.

JUDY WOODRUFF: EEOC, the Equal Employment Opportunity Commission.

Lisa Senecal, some people are saying that they’re uncomfortable with this #MeToo campaign movement because they’re saying, once again, women are being asked to go public with what happened to them, but there is no promise that there is going to be anything done about it. How do you see this?

LISA SENECAL: I don’t necessarily believe that women are being asked to come forward.

I think this is an opportunity to come forward, if that’s something that women want to do, but there’s no obligation to do it. And there’s been a lot of support for letting women know that if this isn’t something you’re comfortable with at this time, no one is obligated to tell their story, and no one is allowed to force you to tell your story before you’re ready.

But the stories are important. Without them, the degree to which this happens across all industries, across genders as well — we know that this happens to men. This happens to the transgender.

It’s not specific to women, although it affects us most frequently. Until we have a critical mass of women who are able to get the men in their lives, the men that they work with to understand how pervasive a problem it is, and then can get men to begin to act on this, because this isn’t a women’s issue.

This is a violence issue, and an issue of power and who has the power. So until the people who still primarily do hold the power, which is primarily men and primarily white men, until they’re going to begin to act, then the problems are going to persist.

JUDY WOODRUFF: Melissa Silverstein, how do you see that? What is it going to take for this to be a change?

MELISSA SILVERSTEIN: The fact that we’re having a global conversation about sexual harassment — I have been doing media for the last week all over the world.

People are really enthralled by this and want to see change. This is a global issue. And, also, Hollywood is a global industry. Seventy cents of every dollar of Hollywood studio movies are made outside the United States.

So what people are looking for is Hollywood to step up. And, today, we had a leader in Hollywood, Kathleen Kennedy, to say we need to have a commission, cross-industry commission, of people who are going to look into this and put a stop to it once and for all.

JUDY WOODRUFF: And pick up on that, Fatima Goss Graves. Just across the board, what is it going to take?

FATIMA GOSS GRAVES: Right.

We know that there are things that would make a difference here. If employers had processes that their employees actually use, you wouldn’t have harassment in the shadows. Right now, most people don’t report harassment to anyone. And it’s because they think their employers won’t do anything, or, worse, that they would experience retaliation.

JUDY WOODRUFF: And that’s — because that’s been what happened.

FATIMA GOSS GRAVES: And that is. They’re right to believe that they will experience retaliation, because they do. They’re shamed. They’re blamed.

But employees could make a difference. Right? They can be — take it seriously and communicate that to their workplace. They can also have the right policies that are in place. And, finally, they could, when someone comes forward, be really clear that they take it seriously and that they will not tolerate retaliation.

Those are things that aren’t happening among employers frequently enough.

JUDY WOODRUFF: Lisa Senecal, as somebody who had it happen to you in a business environment, what changes need to be made in the workplace? What has to happen?

LISA SENECAL: Well, I agree completely with what was just said.

Too often, the workplace education that goes on is incredibly insufficient. It’s more of companies wanting to be able to check the box and say that they did their sexual harassment training. And it isn’t truly something within the culture of companies that they believe that this is a problem and that it is a right of all people working at that company not to be harassed.

So, until it starts to be taken more seriously, and when a woman or anyone comes forward with an accusation, it does have to be taken so much more seriously. And the knee-jerk response, as was in my case, cannot be to shame the woman, can’t be to blame her for somehow bringing this on herself, and putting women back in a position of being victimized a second time because they’re not taken seriously when they come forward.

JUDY WOODRUFF: Melissa Silverstein, yes, go ahead.

MELISSA SILVERSTEIN: I just wanted to add, one of the things that’s so fundamental about this is how this — how it’s so normalized for all of us to go through this kind of harassment, especially in Hollywood, and how people kind of laugh off, oh, you know, that’s locker room talk, or, you know, this is the movie business, get used to it.

And what we need to do is really pierce that veil of the normalization of this kind of conduct, because it starts with, you know, the comments, and then it can escalate very quickly.

So we really need to just change people’s attitudes and get rid of the toxic masculinity. Hollywood has no much institutionalized sexism that sometimes I feel like we need to just start over, if possible.

JUDY WOODRUFF: Joining us also is Leigh Gilmore, a professor at Wellesley College who’s written a book about why — titled “Why We Doubt What Women Say About Their Lives.”

Leigh Gilmore, why don’t women — why haven’t women been believed and taken seriously on this, and could we now be at a moment when they are?

LEIGH GILMORE, Wellesley College: It’s good to be with you, Judy.

I think we have a persistent and a pervasive culture of doubting what women say, especially when they’re bringing forward accounts of harm into the public sphere. So we have these pre-made default cultural narratives of women’s unreliability. We have he said/she said, which is a false equivalence narrative.

We have that notion that nobody knows what really happened. We have that notion that you can’t really trust what women say. None of these are based in fact, but they are part of a kind of cloud that enables us to doubt any woman before she speaks up.

And it’s quite intimidating. And so, if we’re at a point of change, we really are at a moment where I think we have a new level of visibility, and we have the opportunity to amplify the voices of women who are speaking out.

So, insofar as we have that opportunity, there is a form of solidarity, and more women speaking can lead to change.

JUDY WOODRUFF: Fatima Goss Graves, as somebody who works on these issues from a legal standpoint, are we, could we be at a watershed point, or is it just a whole lot more complicated?

FATIMA GOSS GRAVES: Well, the culture change typically has to go together with both the enforcement of the laws and the policy change.

And so we’re at a tipping point, surely, on culture change. But I will tell you, you know, the National Women’s Law Center runs a hot line. And over the last two weeks, we have had double the intake on harassment.

And we have a new network called the Legal Network for Gender Equity, so we’re — attorneys are joining with us and will be ready to take these cases. But those people who are making these calls and contacting us, I think that that shows that you have people who are ready to come forward on social media, and there is power there, but it seems like there are people who are ready to come forward in other ways, too.

JUDY WOODRUFF: I want to quickly go around and ask each one of you about the role of men in all of this.

Lisa Senecal?

LISA SENECAL: Oh, I think it’s critical for men as allies to be coming forward and supporting women who do come forward.

Men also need to be willing to call out other men, whether that’s one-on-one, whether it’s in a group setting within a company, or socially. If a man hears, sees someone doing something inappropriate, they need to have the courage to stand up, even in front of other men, and say, it’s not OK, it’s inappropriate behavior, and it’s not going to be tolerated.

And until it’s also men joining in, women can’t do this by themselves. There is an organization, A Call to Men, that I’m a big fan of. And one of their mantras is, if women could have stopped abuse and assault, they would have done it already.

And that’s completely true. It’s not something that women are going to be able to do alone. It shouldn’t be looked at as only a women’s issue. And until people look at this on a larger scale and understand that this affects the bottom line of companies, it affects productivity, it affects, you know, absenteeism, just across the board, this is not a women’s issue.

It is a human issue.

JUDY WOODRUFF: Right.

Melissa Silverstein, what about that?

And we should point out that men are themselves the victims of sexual harassment and abuse at times.

MELISSA SILVERSTEIN: I feel that this is on men.

The men are most of the perpetrators. They’re also the collaborators. And, at The Weinstein Company, their board was all men, and they were all complicit in creating an environment that allowed this to thrive.

In Hollywood, there’s not a single woman, even the people at the tippy-top of the industry, who don’t report to men. This is also about getting more women into leadership positions and getting the men — and holding the men accountable.

The men in this industry need to step up. They need to say, we want to be — we want to create this industry in a way that women can thrive and don’t have to experience this anymore.

JUDY WOODRUFF: Leigh Gilmore?

LEIGH GILMORE: We’re talking about awareness and accountability.

So, as wonderful as it is to have increased visibility, and it enables us to connect the dots and to see the long histories of sexual abuse, harassment and discrimination, we need new levels of accountability.

I will echo the notion that Harvey Weinstein’s board certainly knew about these accusations. There’s a DA who failed to charge him. We have ample examples of failures.

And what we really need to do is to correct those. The role of men is certainly important here. Minimally, they can show up and be witnesses.

JUDY WOODRUFF: And, finally, Fatima Goss Graves, the role of men and how we prevent this.

FATIMA GOSS GRAVES: We have had a little bit of conversation about men as survivors, but the conversation we haven’t really had is about what happens when men are abusers or enablers or allow this to happen in the workplaces, in schools, or in women’s everyday lives?

And so now we have an opportunity culturally for that conversation. That culture is going to have to hit where policy-makers are. It’s going to have to hit where employers are in order to make a real difference.

JUDY WOODRUFF: Well, it’s clear that everyone is hoping this is a watershed moment, that things will change as a result of what’s happened here. But we will see.

And we appreciate all of you joining us in this conversation, Fatima Goss Graves here with me in Washington, Lisa Senecal, Melissa Silverstein, and Leigh Gilmore.

We thank you all.

FATIMA GOSS GRAVES: Thank you.

MELISSA SILVERSTEIN: Thank you.

The post As survivors say #MeToo, what will it take to stop widespread sexual harassment? appeared first on PBS NewsHour.




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Don't disrespect Alan Turing by reanimating him with AI

Plans to create an interactive AI model of the legendary code breaker Alan Turing are reckless and problematic, says Matthew Sparkes




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Man Utd fans DESPERATE for Alexis Sanchez to CELEBRATE if he scores against Arsenal

ALEXIS SANCHEZ returns to former club Arsenal tonight - and Manchester United fans are desperate to see him celebrate if he scores at the Emirates..





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Adam Peaty accused of disrespecting Commonwealth Games after roaring into breaststroke final

Adam Peaty roared back at those writing him off after cruising through his 50 metres breaststroke semi-final – but was later accused of being disrespectful towards Commonwealth Games competitors.

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Contrite Adam Peaty fights back to win Commonwealth Games gold after ‘disrespect’ controversy

  • Adam Peaty is right about Commonwealths not being the pinnacle
  • Peaty accused of disrespecting Games after roaring into 50m final
  • British Cycling ‘confident’ they can replace Kenny if she retires
  • Englishman Jake Jarman wins fourth gymnastics gold medal
  • Daily Games schedule – plus key events to watch out for
  • ]]>



    • topics:events/commonwealth-games
    • structure:sport
    • topics:events/birmingham-commonwealth-games-2022
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    Questionable Enrollment Math(s) - the Authors Respond

    The authors of the study I blogged about on Monday were kind enough to post a lengthy comment, responding in part to some of the issues I raised. I thought their response was interesting, and so reprint it in its entirety below, interjecting my own reactions as well.

    There were a number of points you made in your blog and the title of questionable maths was what caught our eye and so we reply on facts and provide context.

    Firstly, this is a UK study where the vast majority of UK clinical trials take place in the NHS. It is about patient involvement in mental health studies - an area where recruitment is difficult because of stigma and discrimination.

    I agree, in hindsight, that I should have titled the piece “questionable maths” rather than my Americanized “questionable math”. Otherwise, I think this is fine, although I’m not sure that anything here differs from my post.

    1. Tripling of studies - You dispute NIHR figures recorded on a national database and support your claim with a lone anecdote - hardly data that provides confidence. The reason we can improve recruitment is that NIHR has a Clinical Research Network which provides extra staff, within the NHS, to support high quality clinical studies and has improved recruitment success.

    To be clear, I did not “dispute” the figures so much as I expressed sincere doubt that those figures correspond with an actual increase in actual patients consenting to participate in actual UK studies. The anecdote explains why I am skeptical – it's a bit like I've been told there was a magnitude 8 earthquake in Chicago, but neither I nor any of my neighbors felt anything. There are many reasons why reported numbers can increase in the absence of an actual increase. It’s worth noting that my lack of confidence in the NIHR's claims appears to be shared by the 2 UK-based experts quoted by Applied Clinical Trials in the article I linked to.

    2. Large database: We have the largest database of detailed study information and patient involvement data - I have trawled the world for a bigger one and NIMH say there certainly isn't one in the USA. This means few places where patient impact can actually be measured
    3. Number of studies: The database has 374 studies which showed among other results that service user involvement increased over time probably following changes by funders e.g. NIHR requests information in the grant proposal on how service users have been and will be involved - one of the few national funders to take this issue seriously.

    As far as I can tell, neither of these points is in dispute.

    4. Analysis of patient involvement involves the 124 studies that have completed. You cannot analyse recruitment success unless then.

    I agree you cannot analyze recruitment success in studies that have not yet completed. My objection is that in both the KCL press release and the NIHR-authored Guardian article, the only number mentioned in 374, and references to the recruitment success findings came immediately after references to that number. For example:

    Published in the British Journal of Psychiatry, the researchers analysed 374 studies registered with the Mental Health Research Network (MHRN).
    Studies which included collaboration with service users in designing or running the trial were 1.63 times more likely to recruit to target than studies which only consulted service users.  Studies which involved more partnerships - a higher level of Patient and Public Involvement (PPI) - were 4.12 times more likely to recruit to target.

    The above quote clearly implies that the recruitment conclusions were based on an analysis of 374 studies – a sample 3 times larger than the sample actually used. I find this disheartening.

    The complexity measure was developed following a Delphi exercise with clinicians, clinical academics and study delivery staff to include variables likely to be barriers to recruitment. It predicts delivery difficulty (meeting recruitment & delivery staff time). But of course you know all that as it was in the paper.

    Yes, I did know this, and yes, I know it because it was in the paper. In fact, that’s all I know about this measure, which is what led me to characterize it as “arbitrary and undocumented”. To believe that all aspects of protocol complexity that might negatively affect enrollment have been adequately captured and weighted in a single 17-point scale requires a leap of faith that I am not, at the moment, able to make. The extraordinary claim that all complexity issues have been accounted for in this model requires extraordinary evidence, and “we conducted a Delphi exercise” does not suffice.  

    6. All studies funded by NIHR partners were included – we only excluded studies funded without peer review, not won competitively. For the involvement analysis we excluded industry studies because of not being able to contact end users and where inclusion compromised our analysis reliability due to small group sizes.

    It’s only that last bit I was concerned about. Specifically, the 11 studies that were excluded due to being in “clinical groups” that were too small, despite the fact that “clinical groups” appear to have been excluded as non-significant from the final model of recruitment success.

    (Also: am I being whooshed here? In a discussion of "questionable math" the authors' enumeration goes from 4 to 6. I’m going to take the miscounting here as a sly attempt to see if I’m paying attention...)

    I am sure you are aware of the high standing of the journal and its robust peer review. We understand that our results must withstand the scrutiny of other scientists but many of your comments were unwarranted. This is the first in the world to investigate patient involvement impact. No other databases apart from the one held by the NIHR Mental Health Research Network is available to test – we only wish they were.

    I hope we can agree that peer review – no matter how "high standing" the journal – is not a shield against concern and criticism. Despite the length of your response, I’m still at a loss as to which of my comments specifically were unwarranted.

    In fact, I feel that I noted very clearly that my concerns about the study’s limitations were minuscule compared to my concerns about the extremely inaccurate way that the study has been publicized by the authors, KCL, and the NIHR. Even if I conceded every possible criticism of the study itself, there remains the fact that in public statements, you
    1. Misstated an odds ratio of 4 as “4 times more likely to”
    2. Overstated the recruitment success findings as being based on a sample 3 times larger than it actually was
    3. Re-interpreted, without reservation, a statistical association as a causal relationship
    4. Misstated the difference between the patient involvement categories as being a matter of merely “involving just one or two patients in the study team”
    And you did these consistently and repeatedly – in Dr Wykes's blog post, in the KCL press release, and in the NIHR-written Guardian article.

    To use the analogy from my previous post: if a pharmaceutical company had committed these acts in public statements about a new drug, public criticism would have been loud and swift.

    Your comment on the media coverage of odds ratios is an issue that scientists need to overcome (there is even a section in Wikipedia).

    It's highly unfair to blame "media coverage" for the use of an odds ratio as if it were a relative risk ratio. In fact, the first instance of "4 times more likely" appears in Dr Wykes's own blog post. It's repeated in the KCL press release, so you yourselves appear to have been the source of the error.

    You point out the base rate issue but of course in a logistic regression you also take into account all the other variables that may impinge on the outcome prior to assessing the effects of our key variable patient involvement - as we did – and showed that the odds ratio is 4.12 - So no dispute about that. We have followed up our analysis to produce a statement that the public will understand. Using the following equations:
    Model predicted recruitment lowest level of involvement exp(2.489-.193*8.8-1.477)/(1+exp(2.489-.193*8.8-1.477))=0.33
    Model predicted recruitment highest level of involvement exp(2.489-.193*8.8-1.477+1.415)/(1+exp(2.489-.193*8.8-1.477+1.415)=0.67
    For a study of typical complexity without a follow up increasing involvement from the lowest to the highest levels increased recruitment from 33% to 66% i.e. a doubling.

    So then, you agree that your prior use of “4 times more likely” was not true? Would you be willing to concede that in more or less direct English?

    This is important and is the first time that impact has been shown for patient involvement on the study success.
    Luckily in the UK we have a network that now supports clinicians to be involved and a system for ensuring study feasibility.
    The addition of patient involvement is the additional bonus that allows recruitment to increase over time and so cutting down the time for treatments to get to patients.

    No, and no again. This study shows an association in a model. The gap between that and a causal relationship is far too vast to gloss over in this manner.

    In summary, I thank the authors for taking the time to response, but I feel they've overreacted to my concerns about the study, and seriously underreacted to my more important concerns about their public overhyping of the study. 

    I believe this study provides useful, though limited, data about the potential relationship between patient engagement and enrollment success. On the other hand, I believe the public positioning of the study by its authors and their institutions has been exaggerated and distorted in clearly unacceptable ways. I would ask the authors to seriously consider issuing public corrections on the 4 points listed above.





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