The human major histocompatibility complex (MHC) is a ~4 Mb genomic segment on Chromosome 6 that plays a pivotal role in the immune response. Despite its importance in various traits and diseases, its complex nature makes it challenging to accurately characterize on a routine basis. We present a novel approach allowing targeted sequencing and de novo haplotypic assembly of the MHC region in heterozygous samples, using long-read sequencing technologies. Our approach is validated using two reference samples, two family trios, and an African-American sample. We achieved excellent coverage (96.6%–99.9% with at least 30x depth) and high accuracy (99.89%–99.99%) for the different haplotypes. This methodology offers a reliable and cost-effective method for sequencing and fully characterizing the MHC without the need for whole-genome sequencing, facilitating broader studies on this important genomic segment and having significant implications in immunology, genetics, and medicine.

BACKGROUND:Practice on fasting prior to extubation in critically ill patients is variable. Efficacy of fasting in reducing gastric volume has not been well established. The primary objective of this study was to assess the effect of 4 h of fasting on prevalence of empty stomach using gastric ultrasonography in critically ill subjects who are fasted for extubation. The secondary objectives were to evaluate the change in gastric volumes during 4 h of fasting and to determine factors associated with empty stomach after fasting.METHODS:This was a single-center, prospective, observational study on adult ICU subjects who were enterally fed for at least 6 h continuously and mechanically ventilated. Gastric ultrasound was performed immediately prior to commencement of fasting, after 4 h of fasting, and after nasogastric (NG) aspiration after 4 h of fasting. An empty stomach was defined as a gastric volume ≤ 1.5 mL/kg.RESULTS:Forty subjects were recruited, and 38 (95%) had images suitable for analysis. The prevalence of empty stomach increased after 4 h of fasting (25 [65.8%] vs 31 [81.6%], P = .041) and after 4 h of fasting with NG aspiration (25 [65.8%] vs 34 [89.5%], P = .008). There was a significant difference in median (interquartile range) gastric volume per body weight between before fasting and 4 h after fasting (1.0 [0.5–1.8] mL/kg vs 0.4 [0.2–1.0] mL/kg, P < .001). No patient factors were associated with higher prevalence of empty stomach after 4 h of fasting.CONCLUSIONS:Most mechanically ventilated subjects had empty stomachs prior to fasting for extubation. Fasting for 4 h further increased the prevalence of empty stomach at extubation to > 80%.

For clean-room technologies such as isolators and restricted access barrier systems (RABS), decontamination using hydrogen peroxide (H₂O₂) is increasingly attractive to fulfill regulatory requirements. Several approaches are currently used, ranging from manual wipe disinfection to vapor phase hydrogen peroxide (VPHP) or automated nebulization sanitization. Although the residual airborne H₂O₂ concentration can be easily monitored, detection of trace H₂O₂ residues in filled products is rather challenging. To simulate the filling process in a specific clean room, technical runs with water for injection (WfI) are popular. Thus, the ability to detect traces of H₂O₂ in water is an important prerequisite to ensure a safe and reliable use of H₂O₂ for isolator or clean room decontamination. The objective of this study was to provide a validated quantitative, fluorometric Amplex UltraRed assay, which satisfies the analytical target profile of quantifying H₂O₂ in WfI at low nanomolar to low micromolar concentrations (ppb range) with high accuracy and high precision. The Amplex UltraRed technology provides a solid basis for this purpose; however, no commercial assay kit that fulfills these requirements is available. Therefore, a customized Amplex UltraRed assay was developed, optimized, and validated. This approach resulted in an assay that is capable of quantifying H₂O₂ in WfI selectively, sensitively, accurately, precisely, and robustly. This assay is used in process development and qualification approaches using WfI in H₂O₂-decontaminated clean rooms and isolators.

Obidoxime chloride is an antidote for nerve gas intoxication. As an emergency medicine, it is being stored by the Israel Defense Forces (IDF) scattered throughout Israel in depots without a controlled environment (field conditions), thus being exposed to high and fluctuating temperatures. These conditions do not meet the manufacturer’s requirements. In addition, due to possible supply shortages, the utilization of expired batches was suggested. The current work investigated these matters. Long-term (15 years) storage under different conditions was initiated. Chemical stability and toxicity in rats were assessed. No difference was found between field conditions vs the controlled environment. The obidoxime assay remained >95% for 5 years and >90% for 7 years. The pH remained above the lower specification limit for 7–8 years. The major degradation product, 4-pyridinealdoxime, surpassed the allowed limit at 5 years. The content of total unknown impurities reached its maximum allowed by the IDF limit at 4–5 years. Threefold higher than clinically utilized doses of valid-to-date Toxogonin batches administered to rats did not cause any abnormality. However, expired batches produced significant toxic effects. Although no difference was found between storage of obidoxime ampoules when adhering to manufacturer’s recommendations vs field conditions, accumulation of degradants over the limit allowed by the IDF at 4–5 years of storage and the toxicity of the expired batches observed in rats led the IDF to a decision to shorten the shelf-life of this product from 5 to 4 years when stored in an uncontrolled environment of the Mediterranean climate.

Recent studies have demonstrated promising results of fibroblast activation protein (FAP) inhibitor (FAPI) PET in prognosticating and monitoring interstitial lung diseases (ILDs). As a first step toward successful translation, our primary aim was to validate the FAPI PET uptake through immunohistochemistry in patients with advanced ILD who underwent lung transplantation after a FAPI PET scan. Methods: This is a preliminary analysis of a single-center, open-label, single-arm, prospective exploratory biodistribution study of ⁶⁸Ga-FAPI-46 PET imaging in patients with ILD (NCT05365802). Patients with ILD confirmed by high-resolution CT and scheduled for lung transplant were included. Tissue samples of explanted lungs were obtained from both the central and peripheral lung parenchyma of each lobe. Additional samples were obtained from areas of the lung corresponding to regions of FAPI PET activity. Immunohistochemical staining was performed with an anti-FAP antibody. Percentages of FAP immunohistochemistry-positive area were measured semiautomatically using QuPath software. SUVs in the areas of pathologic samples were measured on FAPI PET/CT by referencing the gross photomap of the explanted lung. A Spearman correlation coefficient test was used to assess the relationship between FAPI PET uptake and FAP immunohistochemical expression in each specimen. Results: Four patients with advanced ILD who underwent FAPI PET/CT before lung transplantation were included. The types of ILD were idiopathic pulmonary fibrosis (n = 2), rheumatoid arthritis–associated ILD (n = 1), and nonspecific interstitial pneumonia (n = 1). FAPI uptake was visualized mainly in the fibrotic area on CT. Twenty-nine surgical pathology samples from 3 patients were analyzed. FAP staining was predominantly positive in fibroblastic foci. FAPI PET SUV_max and SUV_mean showed a positive correlation with the immunohistochemical FAP expression score (SUV_max: r = 0.57, P = 0.001; SUV_mean: r = 0.54, P = 0.002). Conclusion: In this analysis conducted in patients who underwent lung transplantation after a FAPI PET scan, FAPI PET uptake was positively correlated with FAP immunohistochemistry. These findings provide a rationale for further investigation of FAPI PET as a potential imaging biomarker for ILD.

BACKGROUND AND PURPOSE:

Neuronal ceroid lipofuscinoses are a group of neurodegenerative disorders. Recently, enzyme replacement therapy (ERT) was approved for neuronal ceroid lipofuscinosis type 2 (CLN2), a subtype of neuronal ceroid lipofuscinoses. The aim of this study was to quantify brain volume loss in CLN2 disease in patients on ERT in comparison with a natural history cohort using MRI.

BACKGROUND AND PURPOSE:

Hemangioblastoma is a rare vascular tumor that occurs within the central nervous system in children. Differentiating hemangioblastoma from other posterior fossa tumors can be challenging on imaging, and preoperative diagnosis can change the neurosurgical approach. We hypothesize that a "lightbulb sign" on the arterial spin-labeling (ASL) sequence (diffuse homogeneous intense hyperperfusion within the solid component of the tumor) will provide additional imaging finding to differentiate hemangioblastoma from other posterior fossa tumors.

BACKGROUND AND PURPOSE:

World Health Organization (WHO) grade 2 and 3 diffuse gliomas account for approximately 5% of primary brain tumors. They are invasive and infiltrative tumors and have considerable morbidity, causing progressive neurologic deterioration. The mean survival time is <10 years from diagnosis. Surgical debulking represents first-line management. The extent of resection is associated with progression-free and overall survival. Radiologic assessment of the extent of resection is challenging. This can be underestimated on early postoperative MRI, meaning that accurate assessment may be achieved only on delayed follow-up imaging. We hypothesized that DWI may help facilitate more reliable estimates of the extent of resection on early postoperative MRI. This study aimed to assess the utility of DWI in early postoperative MRI to evaluate the extent of resection.

BACKGROUND AND PURPOSE:

Preoperative assessment of meningioma consistency is beneficial for optimizing surgical strategy and prognosis of patients. We aim to develop a noninvasive prediction model for meningioma consistency utilizing MR elastography and DTI.

SUMMARY:

The 2021 World Health Organization Classification of Tumors of the Central Nervous System (CNS5), introduced significant changes, impacting tumors ranging from glial to ependymal neoplasms. Ependymal tumors were previously classified and graded based on histopathology, which had limited clinical and prognostic utility. The updated CNS5 classification now divides ependymomas into 10 subgroups based on anatomic location (supratentorial, posterior fossa, and spinal compartment) and genomic markers. Supratentorial tumors are defined by zinc finger translocation associated (ZFTA) (formerly v-rel avian reticuloendotheliosis viral oncogene [RELA]), or yes-associated protein 1 (YAP1) fusion; posterior fossa tumors are classified into groups A (PFA) and B (PFB), spinal ependymomas are defined by MYCN amplification. Subependymomas are present across all these anatomic compartments. The new classification kept an open category of "not elsewhere classified" or "not otherwise specified" if no pathogenic gene fusion is identified or if the molecular diagnosis is not feasible. Although there is significant overlap in the imaging findings of these tumors, a neuroradiologist needs to be familiar with updated CNS5 classification to understand tumor behavior, for example, the higher tendency for tumor recurrence along the dural flap for ZFTA fusion-positive ependymomas. On imaging, supratentorial ZFTA-fused ependymomas are preferentially located in the cerebral cortex, carrying predominant cystic components. YAP1-MAMLD1-fused ependymomas are intra- or periventricular with prominent multinodular solid components and have significantly better prognosis than ZFTA-fused counterparts. PFA ependymomas are aggressive paramedian masses with frequent calcification, seen in young children, originating from the lateral part of the fourth ventricular roof. PFB ependymomas are usually midline, noncalcified solid-cystic masses seen in adolescents and young adults arising from the fourth ventricular floor. PFA has a poorer prognosis, higher recurrence, and higher metastatic rate than PFB. Myxopapillary spinal ependymomas are now considered grade II due to high recurrence rates. Spinal-MYCN ependymomas are aggressive tumors with frequent leptomeningeal spread, relapse, and poor prognosis. Subependymomas are noninvasive, intraventricular, slow-growing benign tumors with an excellent prognosis. Currently, the molecular classification does not enhance the clinicopathologic understanding of subependymoma and myxopapillary categories. However, given the molecular advancements, this will likely change in the future. This review provides an updated molecular classification of ependymoma, discusses the individual imaging characteristics, and briefly outlines the latest targeted molecular therapies.

T-lymphoblastic lymphoma (T-LLy) is the most common lymphoblastic lymphoma in children and often presents with a mediastinal mass. Lymphomatous suprarenal masses are possible but rare. Here, we discuss the case of a previously healthy 3-yr-old male who presented with mediastinal T-LLy with bilateral suprarenal masses. Following initial treatment, surgical biopsy of persisting adrenal masses revealed bilateral neuroblastoma (NBL). A clinical genetics panel for germline cancer predisposition did not identify any pathogenic variants. Combination large panel (864 genes) profiling analysis in the context of a precision oncology study revealed two novel likely pathogenic heterozygous variants: SMARCA4 c.1420-1G > T p.? and EZH2 c.1943G > C p.(Ile631Phefs*44). Somatic analysis revealed potential second hits/somatic variants in EZH2 (in the T-LLy) and a segmental loss in Chromosome 19p encompassing SMARCA4 (in the NBL). Synchronous cancers, especially at a young age, warrant genetic evaluation for cancer predisposition; enrollment in a precision oncology program assessing germline and tumor DNA can fulfill that purpose, particularly when standard first-line genetic testing is negative and in the setting of tumors that are not classic for common cancer predisposition syndromes.

Vision is initiated by capturing photons in highly specialized sensory cilia known as the photoreceptor outer segment. Because of its lipid and protein composition, the outer segments are prone to photo-oxidation, requiring photoreceptors to have robust antioxidant defenses and high metabolic synthesis rates to regenerate the outer segments every 10 days. Both processes required high levels of glucose uptake and utilization. Retinitis pigmentosa is a prevalent form of inherited retinal degeneration characterized by initial loss of low-light vision caused by the death of rod photoreceptors. In this disease, rods die as a direct effect of an inherited mutation. Following the loss of rods, cones eventually degenerate, resulting in complete blindness. The progression of vision loss in retinitis pigmentosa suggested that rod photoreceptors were necessary to maintain healthy cones. We identified a protein secreted by rods that functions to promote cone survival, and we named it rod-derived cone viability factor (RdCVF). RdCVF is encoded by an alternative splice product of the nucleoredoxin-like 1 (NXNL1) gene, and RdCVF was found to accelerate the uptake of glucose by cones. Without RdCVF, cones eventually die because of compromised glucose uptake and utilization. The NXNL1 gene also encodes for the thioredoxin RdCVFL, which reduces cysteines in photoreceptor proteins that are oxidized, providing a defense against radical oxygen species. We will review here the main steps of discovering this novel intercellular signaling currently under translation as a broad-spectrum treatment for retinitis pigmentosa.

Missing or inaccessible lung function measurements, gathered over time, have the potential to stagnate or impair clinical care decisions being made. This jeopardises patient safety and often contributes to excessive resource utilisation. Data integration is fundamental to clinical decision-making and entails amalgamating lung function data from multiple sources in a user-friendly format. Despite this, current systems for recording lung function data are suboptimal, with copious gaps in the clinical picture arising from missing or inaccessible lung function measurements. This article discusses the importance of data integration for lung function, with a call to action for key stakeholders involved in the performance, management and interpretation of such tests.

Advancements in immunotherapy in the perioperative setting have revolutionised the treatment of resectable nonsmall cell lung cancer (NSCLC). Here we present the methodology and results of the clinical trial CheckMate 816 demonstrating the benefit of neoadjuvant therapy with nivolumab plus chemotherapy compared with chemotherapy alone. Furthermore, this article discusses the implications for future practice in resectable NSCLC and the need for future research.

Cassian's on a new mission to steal a familiar ship in the next season of his self-titled Star Wars show.

Trump seems to have just two options.

Former MP Joanna Cherry has said that the SNP rules which prevented her from standing for a seat at Holyrood would not block Stephen Flynn from doing the same.  

Jason and Robert have a weeb-off. Kelley dies for two days and wakes up in her own sweat. Chris goes to a store that's half comics, half anime, and half body pillows. Bullseye!

The post RPG Cast – Episode 674: “Stop Sending Dragons, I Have Things to Do” appeared first on RPGamer.

Sony has released the US and European PlayStation Store downloads charts for September 2024.

Call of Duty: Black Ops 6 topped the PlayStation 5 charts in the US and Canada, as well as on the European charts. Dragon Ball: Sparking! Zero was number two in the US and Canada, as well as in Europe. Undisputed was number three in the US and Canada, while it was EA Sports FC 25 in Europe.

Call of Duty: Black Ops 6 was the most downloaded game on the PlayStation 4 charts in the US and Canada, while it was EA Sports FC 25 on the European charts. Minecraft was number two in the US and Canada, while it was Call of Duty: Black Ops 6 in Europe. Red Dead Redemption 2 was number three in the US and Canada, while it was The Forest in Europe.

Arizona Sunshine Remake topped the PlayStation VR2 charts in the US and Canada, as well as in Europe. Beat Saber VR was number two in the US and Canada, while it was The Dark Pictures: Switchback VR in Europe. The Dark Pictures: Switchback VR was number three in the US and Canada, while it was Metro Awakening in Europe.

ASTRO BOT Rescue Mission topped the PlayStation VR charts in the US and Canada, while it was Batman: Arkham VR in Europe. The Elder Scrolls V: Skyrim VR was number two in the US and Canada, while it was The Exorcist: Legion VR in Europe.

Throne and Liberty topped the free-to-play US and Canada charts, and in Europe. Fortnite was number two in the US and Canada, and in Europe.

Here is the complete list of charts:

PS5 Games

PS4 Games

PS VR2 Games*

PS VR Games

Free to Play (PS5 + PS4)

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/463025/call-of-duty-black-ops-6-tops-the-ps5-ps-store-download-charts-in-october/

Liam Payne was seemingly having a “lovely day in Argentina” just hours before his death on Wednesday, according to what appear to be a series of final posts made to his Snapchat account.

The former One Direction member was found dead in the courtyard of a Buenos Aires hotel, having apparently plunged 13 to 14 meters from his balcony, according to local police. A cause of death has not officially been determined, and it was unclear whether the fall was accidental or intentional.

On his Snapchat Story, however, it would have appeared to any fan that Payne was having a relaxing vacation. In since-deleted posts in the hours before his death, he posted a front-facing video in which he told followers, “It’s a lovely day here in Argentina. This is the breakfast table. Just enjoying coffee and breakfast even though it’s 1 p.m.”

Read more at The Daily Beast.

It appears Donald Trump is once again attempting to silence Stormy Daniels, despite his recent convictions in that category.

MSNBC’s Rachel Maddow reports that Trump’s lawyers tried to “get another hush money deal” with the adult film star, to keep her from making any “public or private statements related to any alleged past interactions” with the former president. In exchange for her written agreement, Trump’s team reportedly offered to adjust the debt she owes Trump for the unsuccessful defamation case her lawyer brought against him in 2018.

Daniels still needs to pay “hundreds of thousands of dollars” in legal fees, Maddow explained, and in hammering out the exact amount, Trump’s lawyers allegedly offered to “pretend” she owed their client “less than they actually believed” she did. Whereas they first estimated Daniels’ debt at $650,000, Maddow reported, they said they would settle her tab for $620,000, if she promised not to make any “defamatory or disparaging statements about him, his business, and/or any affiliates, or his suitability as a candidate for president.” They then adjusted the fee, asking $635,000 if she refused to sign a non-disclosure agreement. Daniels reportedly turned them down, paying $627,500 and declining to sign the NDA.

Read more at The Daily Beast.

One of my favourite satires is the Screwtape Letters, an epistolary novel by Narnia scribe C.S. Lewis. It consists of messages from an oily elder demon to his nephew about how to correctly groom the soul of an unsuspecting human being. It's a claustrophobic send-up of managerial politics and nepotism, with World War 1 unfolding in the background. A real pick-me-up. Sintopia is the Two Point incarnation of that premise - in other words, brighter and breezier and definitely more slapstick than Christian. It puts you in charge of a world divided between Earth and hell, and challenges you to ensure a steady movement of optimally sinful souls between one and the other. Say your prayers and watch the trailer.

Read more

Some days, I wonder if every word written before a trailer is actually superfluous. It’s a visual medium, after all. What can a description achieve save to clumsily gesture at the true shape of something; a dog-eared tour brochure for a thrilling weekend spelunking in Plato’s cave? I can usually shake this feeling, but gory zombie action game Showa American Story is my breaking point. There is nothing I can impart about this thing that will not be conveyed better by allowing its new trailer to wash over you like a tide of sheer videogame. Here’s it:

Read more

Put your hand up if you'd forgotten that every Assassin's Creed game is, strictly speaking, set in the present day. I know I had. That's not the actual distant past you're parkouring through. That isn't actual Renaissance architecture you're clambering on. It's a holographic Animus simulation, conjured from ancestral memories flash-frozen within your DNA - convenient, inasmuch as it means that any inconsistencies are your DNA's fault, not Ubisoft's. If the ledge-mantling animations are glitchy, that's simply because you have bad genes.

We can both be forgiven for losing sight of Assassin's Creed's modern day narrative frame. Ubisoft themselves have downplayed it since the era of Desmond Miles, the watery Peter Parker figure who served as puppetmaster protagonist for AC games up to Assassin's Creed 3. In Assassin's Creed Shadows, however, they're planning to bring back the modern day setting in a big way, though details are scanty.

Read more

Back in the misty reaches of time (March) popular farming sim Stardew Valley got a big update that added more pets to the game (it also let you drink mayonaise but let's not get sidetracked). Those new cats, dogs, and turtles had the cute distinction of being able to wear hats, should you choose to kit your wee friends out. Now, following many months of smaller updates to the game, it seems those hats are causing a problem. "[If] you are experiencing performance issues in Stardew Valley 1.6, remove all hats from pets," said creator Eric Barone in a xeet. When asked the lore-accurate cause of this problem, he blamed: "a strange rash".

Read more

In all honesty, Toads Of The Bayou could have been several notches less ribbet-ing than its Steam demo ended up being, because its stylised pixel fly-snatchers are just that good. There’s only one of the three characters available in the freebie (one of the others is a toad nun with a shotgun), but he’s got a little cutlass, a flintlock pistol, and a can-do attitude - at least when it comes to either stabbing or shooting things. The game itself is a little bit deckbuilder, a little bit Into The Breach: turn based strategy with perfect information and various tricks you can pull to make enemies hit each other instead of the thing you’re trying to protect. Indulge yourself on the gourmet tray-tray below.

Read more

The developers of hero shooter Overwatch 2 must have dropped a box full of old photographs while clearing the attic, spilling old snapshots of Route 66 onto the floor and getting snared in a nostalgic daze. The game is launching a "Classic" mode today that will let you play the first-person payload pusher as it (mostly) was back in 2016 when the first Overwatch launched. That means 6v6 fights, the original abilities of its heroes, and no limits to stop the entire team picking the same character.

Read more

After nearly a year of public beta honing, the Nvidia App – Team Green’s new one-stop shop for desktop GPU management – is out in full. Not alongside the upcoming RTX 50 series, as rumoured, but right-now-today-this-minute. I’ve been testing out the launch version and while it’s not without some dud features, it does agreeably achieve its stated goal of combining the functions within Nvidia Control Panel and GeForce Experience. And if installing it means never having to use the latter again, well, that’s 149MB well spent.

Read more

Watch Video | Listen to the Audio

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.

Secretary of State was questioned on Good Morning Britain over the pledge - with host asking 'how much will it have gone up by then?'

Samantha Harvey has won the UK's top fiction prize for a novel that takes place over 24 hours on the International Space Station

Cyborg: A documentary tells the intriguing story of Neil Harbisson, who wears an antenna to “hear” colour, but it is lacking in depth and should have probed its subject more, says Simon Ings

A quantum computing protocol makes it possible to extract energy from seemingly empty space, teleport it to a new location, then store it for later use

What if tech bros ruled the world, asks Asif Kapadia's 2073. This docudrama is captivating and disturbing, but lacks enough heft to stand out

Google, Microsoft and others have taken big steps towards error-free devices, hinting that quantum computers that solve real problems aren’t far away

Researchers have managed to encode enormous amounts of information, including images, into DNA at a rate hundreds of times faster than was previously possible

Agents are being offered double the normal commission to help shift apartments throughout capital cities.

That’s not his deal, you guys.

The finale doesn’t look to provide a definitive answer to what drove Aaron’s actions, much to the show’s credit.

Today, Boston Dynamics and the Toyota Research Institute (TRI) announced a new partnership “to accelerate the development of general-purpose humanoid robots utilizing TRI’s Large Behavior Models and Boston Dynamics’ Atlas robot.” Committing to working towards a general purpose robot may make this partnership sound like a every other commercial humanoid company right now, but that’s not at all that’s going on here: BD and TRI are talking about fundamental robotics research, focusing on hard problems, and (most importantly) sharing the results.

The broader context here is that Boston Dynamics has an exceptionally capable humanoid platform capable of advanced and occasionally painful-looking whole-body motion behaviors along with some relatively basic and brute force-y manipulation. Meanwhile, TRI has been working for quite a while on developing AI-based learning techniques to tackle a variety of complicated manipulation challenges. TRI is working toward what they’re calling large behavior models (LBMs), which you can think of as analogous to large language models (LLMs), except for robots doing useful stuff in the physical world. The appeal of this partnership is pretty clear: Boston Dynamics gets new useful capabilities for Atlas, while TRI gets Atlas to explore new useful capabilities on.

Here’s a bit more from the press release:

The project is designed to leverage the strengths and expertise of each partner equally. The physical capabilities of the new electric Atlas robot, coupled with the ability to programmatically command and teleoperate a broad range of whole-body bimanual manipulation behaviors, will allow research teams to deploy the robot across a range of tasks and collect data on its performance. This data will, in turn, be used to support the training of advanced LBMs, utilizing rigorous hardware and simulation evaluation to demonstrate that large, pre-trained models can enable the rapid acquisition of new robust, dexterous, whole-body skills.

The joint team will also conduct research to answer fundamental training questions for humanoid robots, the ability of research models to leverage whole-body sensing, and understanding human-robot interaction and safety/assurance cases to support these new capabilities.

For more details, we spoke with Scott Kuindersma (Senior Director of Robotics Research at Boston Dynamics) and Russ Tedrake (VP of Robotics Research at TRI).

How did this partnership happen?

Russ Tedrake: We have a ton of respect for the Boston Dynamics team and what they’ve done, not only in terms of the hardware, but also the controller on Atlas. They’ve been growing their machine learning effort as we’ve been working more and more on the machine learning side. On TRI’s side, we’re seeing the limits of what you can do in tabletop manipulation, and we want to explore beyond that.

Scott Kuindersma: The combination skills and tools that TRI brings the table with the existing platform capabilities we have at Boston Dynamics, in addition to the machine learning teams we’ve been building up for the last couple years, put us in a really great position to hit the ground running together and do some pretty amazing stuff with Atlas.

What will your approach be to communicating your work, especially in the context of all the craziness around humanoids right now?

Tedrake: There’s a ton of pressure right now to do something new and incredible every six months or so. In some ways, it’s healthy for the field to have that much energy and enthusiasm and ambition. But I also think that there are people in the field that are coming around to appreciate the slightly longer and deeper view of understanding what works and what doesn’t, so we do have to balance that.

The other thing that I’d say is that there’s so much hype out there. I am incredibly excited about the promise of all this new capability; I just want to make sure that as we’re pushing the science forward, we’re being also honest and transparent about how well it’s working.

Kuindersma: It’s not lost on either of our organizations that this is maybe one of the most exciting points in the history of robotics, but there’s still a tremendous amount of work to do.

What are some of the challenges that your partnership will be uniquely capable of solving?

Kuindersma: One of the things that we’re both really excited about is the scope of behaviors that are possible with humanoids—a humanoid robot is much more than a pair of grippers on a mobile base. I think the opportunity to explore the full behavioral capability space of humanoids is probably something that we’re uniquely positioned to do right now because of the historical work that we’ve done at Boston Dynamics. Atlas is a very physically capable robot—the most capable humanoid we’ve ever built. And the platform software that we have allows for things like data collection for whole body manipulation to be about as easy as it is anywhere in the world.

Tedrake: In my mind, we really have opened up a brand new science—there’s a new set of basic questions that need answering. Robotics has come into this era of big science where it takes a big team and a big budget and strong collaborators to basically build the massive data sets and train the models to be in a position to ask these fundamental questions.

Fundamental questions like what?

Tedrake: Nobody has the beginnings of an idea of what the right training mixture is for humanoids. Like, we want to do pre-training with language, that’s way better, but how early do we introduce vision? How early do we introduce actions? Nobody knows. What’s the right curriculum of tasks? Do we want some easy tasks where we get greater than zero performance right out of the box? Probably. Do we also want some really complicated tasks? Probably. We want to be just in the home? Just in the factory? What’s the right mixture? Do we want backflips? I don’t know. We have to figure it out.

There are more questions too, like whether we have enough data on the Internet to train robots, and how we could mix and transfer capabilities from Internet data sets into robotics. Is robot data fundamentally different than other data? Should we expect the same scaling laws? Should we expect the same long-term capabilities?

The other big one that you’ll hear the experts talk about is evaluation, which is a major bottleneck. If you look at some of these papers that show incredible results, the statistical strength of their results section is very weak and consequently we’re making a lot of claims about things that we don’t really have a lot of basis for. It will take a lot of engineering work to carefully build up empirical strength in our results. I think evaluation doesn’t get enough attention.

What has changed in robotics research in the last year or so that you think has enabled the kind of progress that you’re hoping to achieve?

Kuindersma: From my perspective, there are two high-level things that have changed how I’ve thought about work in this space. One is the convergence of the field around repeatable processes for training manipulation skills through demonstrations. The pioneering work of diffusion policy (which TRI was a big part of) is a really powerful thing—it takes the process of generating manipulation skills that previously were basically unfathomable, and turned it into something where you just collect a bunch of data, you train it on an architecture that’s more or less stable at this point, and you get a result.

The second thing is everything that’s happened in robotics-adjacent areas of AI showing that data scale and diversity are really the keys to generalizable behavior. We expect that to also be true for robotics. And so taking these two things together, it makes the path really clear, but I still think there are a ton of open research challenges and questions that we need to answer.

Do you think that simulation is an effective way of scaling data for robotics?

Tedrake: I think generally people underestimate simulation. The work we’ve been doing has made me very optimistic about the capabilities of simulation as long as you use it wisely. Focusing on a specific robot doing a specific task is asking the wrong question; you need to get the distribution of tasks and performance in simulation to be predictive of the distribution of tasks and performance in the real world. There are some things that are still hard to simulate well, but even when it comes to frictional contact and stuff like that, I think we’re getting pretty good at this point.

Is there a commercial future for this partnership that you’re able to talk about?

Kuindersma: For Boston Dynamics, clearly we think there’s long-term commercial value in this work, and that’s one of the main reasons why we want to invest in it. But the purpose of this collaboration is really about fundamental research—making sure that we do the work, advance the science, and do it in a rigorous enough way so that we actually understand and trust the results and we can communicate that out to the world. So yes, we see tremendous value in this commercially. Yes, we are commercializing Atlas, but this project is really about fundamental research.

What happens next?

Tedrake: There are questions at the intersection of things that BD has done and things that TRI has done that we need to do together to start, and that’ll get things going. And then we have big ambitions—getting a generalist capability that we’re calling LBM (large behavior models) running on Atlas is the goal. In the first year we’re trying to focus on these fundamental questions, push boundaries, and write and publish papers.

I want people to be excited about watching for our results, and I want people to trust our results when they see them. For me, that’s the most important message for the robotics community: Through this partnership we’re trying to take a longer view that balances our extreme optimism with being critical in our approach.

Unknown host Charlie Stone analyzes Trump's unprecedented victory with Obama Homeland Security Secretary, Jeh Johnson

As we share our truths and witness each other's, we build unity and community.

Comet Nishimura (C/2023 P1) was discovered in August and is now whizzing by Earth, but finding it in the sky will be a challenge.

Fisheries and Oceans Canada whale researchers recently spotted one of the largest pods of orca whales ever reported off the coast of Newfoundland and Labrador.

Online group Girls Who Chase has created a global community of women who head into severe weather to record images, report damage and help scientists understand the impact of storms to be better prepared

Every stock trader should consider a virtual private network to safeguard their trading, according to tech guru Kurt "CyberGuy" Knutsson.