Home « Back who attempted to bribe a Minnesota juror with a bag of $120,000 in cash in exchange for an acquittal in one of the country's largest COVID-19-related fraud cases stand outside the federal courthouse in Minneapolis on Sept 5.Alex Kormann | Star Tribune via APGo Deeper.CloseCreate an account or log in to save stories We have added it to a list of your favorite stories The Minnesota State Patrol says Ladan Ali had a blood alcohol concentration of .284 when she rear-ended another driver at low speed on Highway 55 in Mendota Heights on Feb the driver said Ali hit him a second time before fleeing A trooper found Ali stopped in the center lane of traffic on Minnesota Highway 62 near Minneapolis-St Ali “almost fell over” and once inside the squad car “began screaming and hitting the vehicle divider and had removed her handcuffs two different times.” MPR News helps you turn down the noise and build shared understanding Turn up your support for this public resource and keep trusted journalism accessible to all the officer advised Ali to contact an attorney The trooper said that Ali “then sat in her chair and yelled at him at one point dialing on the phone provided and then smacking the phone against the phone base.” She also allegedly hit the machine that the trooper was setting up for a second breath test Ali, 32, pleaded guilty to jury bribery for delivering a Hallmark gift bag with $120,000 to the home of a juror in the first Feeding Our Future trial in June A federal judge scheduled a March 5 hearing to determine whether Ali's pretrial release should be revoked She's due in Hennepin County court the following week on the drunken driving charge Ali is among five people charged in the jury bribery case and the second to plead guilty When she was charged in that case she was listed as being from Seattle she’s listed as living in the Twin Cities suburb of Fridley New court documents unsealed Tuesday show that Ladan Mohamed Ali received at least $1.6 million from other entities involved in the massive fraud scheme according to a document unsealed Tuesday by a federal judge Ladan Mohamed Ali created a food vendor called Afro Produce in St according to corporate filings with the Minnesota Secretary of State one of the country’s largest pandemic-related frauds testified Tuesday in Bock and Salim’s trial that she reviewed the bank records of Afro Produce and “could not quantify whether there was any food purchased at all or if these were just fabricated invoices.” FBI agent Kevin Kane said conspirators used Afro Produce to cover their tracks by submitting “fake invoices” documenting the purchase of food that was never delivered by the St which listed its business address as 2554 Como Av Similar invoices have been the subject of testimony in the trial of Bock and Said with FBI agents showing Afro Produce invoices that claimed to document the purchase of hundreds of thousands of dollars of food by companies accused of defrauding the meals program Kane noted that Ali received a series of “large checks” from Afro Produce in 2021 and 2022 The warrant includes photocopies of three checks totaling $40,000 made out to Ali from Afro Produce said Tuesday that he hadn’t seen the search warrant and declined to comment Ali listed Gar Gaar as her employer when she opened a bank account in 2021 Ali’s next court hearing is Thursday to discuss if she violated conditions of her release after a DWI arrest in February. According to charges filed in Hennepin County District Court, a State Patrol trooper stopped Ali after she rear-ended another car and fled the scene. Her breath test revealed a blood alcohol content of 0.28%. Jeffrey Meitrodt is an investigative reporter for the Star Tribune who specializes in stories involving the collision of business and government regulation.  Twin Cities Suburbs Conservative board members had questioned the content of the books and curricula prompting criticism from the teachers union Doğukan Günaydin was arrested March 27 by plainclothes officers from the U.S Immigration and Customs Enforcement in Minneapolis James Duane Ortley made his first appearance on four counts of second-degree murder and remains jailed on $2 million bail Three men were charged in a separate slaying that took place four blocks away several hours later The woman who pleaded guilty to delivering a bag of cash to a juror in last year’s Feeding Our Future trial is now accused of crashing into another car while drunk was arrested Friday evening after she allegedly drove away from the scene of the crash on Highway 55 near Acacia Boulevard in Mendota Heights the other driver involved in the crash reported that Ali bumped into his car twice and refused to get out of her car The driver said Ali “had heavily slurred speech and was honking her horn” before driving away in her Volkswagen Tiguan A Minnesota State Patrol lieutenant caught up with the Volkswagen which was stopped in the center lane of Highway 62 at Highway 77 The lieutenant “immediately smelled the strong odor of an alcoholic beverage” coming from inside the vehicle and noted Ali had slurred speech glassy eyes and struggled to find her driver’s license Ali “almost fell over” getting out of the car and a preliminary breath test recorded her blood alcohol content at 0.284 Ali is charged with two counts of third-degree DWI failing to give information in a collision and obstructing a peace officer As previously reported, Ali pleaded guilty to one count of bribery of a juror in September after she brought a bag containing $120,000 in cash to the home of a juror during the June trial Ali was on pretrial release while she awaited sentencing in the bribery case but a probation officer on Wednesday filed a petition arguing that her arrest violated the terms of release Any person with disabilities who needs help accessing the content of the FCC Public File may contact KSTP via our online form or call 651-646-5555 White & Case White Collar partner Ladan Stewart counsel Marietou Diouf and law clerk Arianna Skipper examine the state of crypto regulation and enforcement under the Trump administration which they note are "broad outlines of a truly seismic change." The authors point to recent crypto-friendly political appointments the creation of a "President's Working Group on Digital Asset Markets" and the formation of a new SEC crypto task force led by SEC Commissioner Hester Peirce as signaling the administration's intent to work with the industry on developing a more friendly regime and the other steps taken in just its first few weeks make clear that crypto now plays a central role in the new administration's regulatory priorities—a development that may fundamentally change its place in our financial markets," they said "This new collaborative approach will not only result in a welcome end to crypto's antagonistic relationship with US regulators but will also provide opportunities to craft a more practical and constructive regulatory framework for this new innovative and largely untapped asset class while still maintaining the important investor protections that are central to our capital markets." Read the full article here. Prior results do not guarantee a similar outcome Where will the world’s most famous spy go next Does this question even matter anymore to so-called “modern audiences” To answer the second question first, Bond’s future does indeed matter greatly to millions of fans. The Bond films have been viewed by at least 20% of the world’s population his embodiment of Western masculinity (a good thing in my view) — has achieved household status over the decades For Amazon to steward the Bond franchise in good faith, and not just as a soulless money grab à la Disney’s “Star Wars” and Indiana Jones franchises, one thing needs to be clear: James Bond is not just “content,” as former creative controller Barbara Broccoli herself noted Bond is a memory passed down from generation to generation he is an introduction to masculinity — the good showing men how to be the best versions of themselves while also exposing the pitfalls of debauchery Bond should not become just another thumbnail for Amazon’s catalog of movies and television shows He is not just merchandise or a quick marketing tool and Amazon risks alienating a fervent Bond fan base Treat Bond like mere “content,” and the risks will be financial too — lower box office numbers fewer clicks and a steady erosion of Bond’s impact on the culture Just look at what happened to “Star Wars.” Was it better perceived by fans pre-Disney ownership or today with seemingly endless spin-offs that devalue the 1970s-era brand whose final installment — 2023’s “Indiana Jones and the Dial of Destiny” — entered and exited mainstream discourse with barely a whimper For Amazon MGM Studios to succeed as Bond’s steward the company should cater to those who will actually line up on the next film’s opening weekend and watch YouTube reviews of the latest Bond girl The target audience is the fan who may even open an original novel by Ian Fleming exploring the character’s humble origins in print What Bond’s actual fans are not: People who want to fundamentally change the character like and trust the man on the screen — or on the page If Amazon decides instead to appeal to those who’ve suggested making the character female they won’t be targeting fans but a much smaller group that wants to co-opt an iconic character one they deem offensive to modern sensibilities During recent discussions between Broccoli’s Eon Productions and Amazon, one Amazon employee reportedly offered “I don’t think James Bond is a hero.” Her view may represent a vocal minority but it is a minority nonetheless — and one that can’t be effectively monetized Amazon founder Jeff Bezos has asked his followers on X who they want to be the next Bond with Henry Cavill a popular choice early on The path forward for Amazon — and Bond himself — should be common sense: Don’t fix what isn’t broken. Stick to the formula that made the 007 franchise history’s longest running in the first place. It worked for Fleming and the Broccolis. To quote Barbara Broccoli’s father, Cubby, “Whenever you get stuck, go back to Fleming.” Otherwise, James Bond will fade into the past. And Amazon will become Bond’s greatest villain. Luka Ladan, who works in PR, is a die-hard James Bond fan. Insights does not appear on any news articles Subscribe for unlimited accessSite Map Digital Edition Subscribe Archives by Santa Clarita Magazine | Sep 25, 2024 | Medical is a notable figure in the field of medicine bringing a wealth of expertise and compassion to her practice Samadi’s career is marked by her dedication to advancing medical knowledge and improving patient care.Dr Samadi has made significant contributions to her field particularly in the realm of Internal Medicine Her work is characterized by a commitment to excellence and a patient-centered approach which has earned her a reputation as a leader in her field.Her clinical expertise is complemented by a strong focus on research and education underscoring her belief in the importance of ongoing learning and innovation Samadi is known for her ability to translate complex medical concepts into accessible information for patients helping them make informed decisions about their health.Beyond her clinical and research endeavors Samadi is actively involved in community outreach and advocacy reflecting her dedication to making a positive impact beyond the confines of her practice Her work is a testament to her passion for medicine and her unwavering commitment to enhancing the well-being of those she serves.In sum exemplifies the qualities of a distinguished physician—expertise and a tireless commitment to improving healthcare Her contributions to the field are a source of inspiration for both her colleagues and patients alike by Linda, Moe and Alexander Hafizi | May 2, 2025 | A Note From the Publisher   May is a month that invites us to slow down and appreciate all the beauty around us—from blooming flowers to meaningful celebrations with family and friends by Santa Clarita Magazine | May 2, 2025 | Community On our cover of this month’s magazine we are pleased to welcome: Henry Mayo Newhall Hospital President and CEO Kevin Klockenga; Foundation President Marlee Lauffer; Dr Medical Director of Emergency Services and Co-Chair; Dr The Boys & Girls Club of Santa Clarita Valley is delighted to announce its highly anticipated annual auction This year’s Mardi Gras theme promises to transport attendees to a vibrant celebration filled.. Santa Clarita Magazine has set a high standard for excellence in advertising for over 34 years Santa Clarita Magazine has grown with the Santa Clarita Valley since 1990 and become the #1 place to advertise locally For Advertising informationCall or Text: 1 (661) 294-4444 leaves the Minneapolis federal courthouse with defense attorney Eric Newmark on Sept 2024 after pleading guilty to jury bribery.Alex Kormann | Star Tribune via APGo Deeper.CloseCreate an account or log in to save stories Ali pleaded guilty in federal court in September to delivering a Hallmark gift bag containing $120,000 to the home of a juror and promised more cash in exchange for an acquittal The juror called 911 and was excused from the trial That proceeding, and another that’s underway in Minneapolis of Feeding Our Future founder Aimee Bock and former restaurant owner Salim Said are the first trials to stem from a sprawling federal investigation into an alleged $250 million scheme to defraud taxpayer-funded child nutrition programs during the COVID-19 pandemic Five months after Ali entered her guilty plea, Hennepin County prosecutors charged her with DWI for allegedly driving with a blood alcohol concentration of .284, more than three-and-a-half times the legal limit. MPR News helps you turn down the noise and build shared understanding. Turn up your support for this public resource and keep trusted journalism accessible to all. Magistrate Judge Douglas Micko ordered Ali to stay away from bars and liquor stores, undergo alcohol treatment, and submit to periodic breath tests as conditions of her release. Ali, 32, has not been charged in the wider fraud case. But in a search warrant for her cell phone that was unsealed on March 4, FBI special agent Kevin Kane writes that Ali was a signatory on a bank account for Afro Produce, a St. Paul company named in the investigation. The company, which listed an address on Como Avenue, “is a purported food vendor that received millions of dollars from entities involved in the fraudulent scheme to obtain federal child nutrition program funds,” Kane writes. On the same day that a judge unsealed the warrant, FBI forensic accountant Pauline Roase testified at Bock and Said’s trial that invoices and payments recovered from Afro Produce “didn’t even come close” to matching. “I just could not quantify whether there was any food purchased at all, or if these were just fabricated invoices,” Roase said. According to the search warrant, Ali also received multiple checks from Afro Produce in 2021 and 2022 for $10,000 and $20,000 each. The memo lines indicated that the payments were for her “salary” and “consulting.” Ali’s personal bank records allegedly show that she received checks from Gar Gaar Family Services, which was also known as Youth Leadership Academy. The Minnesota Department of Education barred the nonprofit from participating in the child nutrition programs in December 2021 after finding it “seriously deficient.” The following month, the FBI raided Feeding Our Future’s offices, Bock and Said’s homes, and two dozen other locations. In an email to MPR News, defense attorney Eric Newmark declined to comment on the allegations in the search warrant. a Seattle woman who attempted to bribe a Minnesota juror with a bag of $120,000 in cash in exchange for an acquittal in one of the country's largest COVID-19-related fraud cases Courthouse on Thursday in Minneapolis.Alex Kormann | Star Tribune via APGo Deeper.CloseCreate an account or log in to save stories She is one of five charged in the attempted bribery attempt The cash delivery came toward the end of a trial in which jurors heard testimony from seven people connected to the nonprofit Feeding Our Future who were charged with stealing $47 million from taxpayer-funded child nutrition programs ensuring she understood the consequences of the plea deal — including the possibility of a maximum 15-year prison sentence — Ali asserted she understood Ali agreed that she was recruited by Abdimajid Nur to assist in the bribery attempt in exchange for a $150,000 payment flying in from Seattle to assist with the plot Ali admitted she was concerned the plan would fail and had her own scheme to steal some or all of the bribe money She admitted to falsely telling Nur that she met up with juror 52 at a bar and that the juror wanted $500,000 for returning a not guilty verdict Ali never spoke with the juror and the juror never agreed to accept a bribe Ali gave a gift bag with $120,000 to Juror 52’s relative but pocketed the remaining $80,000 planned to be part of the bribery attempt The targeted juror immediately alerted law enforcement of the attempt and was excused from the trial U.S. Attorney for Minnesota Andrew Luger previously compared the plot to a mobster movie and said the alleged conspirators focused on the juror because they believed her to be the youngest and the only juror of color He said the alleged conspirators began researching family members and conducting surveillance to learn her habits followed her and determined that she would succumb,” he said The four others charged with the bribery attempt are: Abdulkarim Shafii Farah The latter three were also defendants in the Feeding Our Future trial Said Farah was acquitted in the earlier trial and Nur has pleaded guilty to the bribery attempt Thompson said he wouldn’t be surprised if the rest pleaded guilty “This is the most bizarre thing I’ve experienced in court by far,” he said The plea deal calculates about a five to six year sentence for Ali but the sentence will ultimately be decided by the judge “From the very beginning I wanted to take responsibility for my actions,” Ali said Doty granted Ali the right to remain released pending her sentencing Ladan Ali admitted to stealing $80,000 in cash meant to go to the juror She could face nearly five to six years in prison three weeks after she followed a juror from the downtown Minneapolis courthouse to her home and left the bag of cash with promises of more money if the juror voted to acquit the defendants Ali had initially pleaded not guilty and was released from custody on supervised release But she changed her plea and admitted to new details that she had pocketed $80,000 given to her by defendants to bribe the juror Ali faces a possible sentence of nearly five to six years in prison in part because she agreed to accept responsibility in the plea agreement She also agreed to forfeit any cash from the scheme and pay a fine of up to $200,000 I wanted to take responsibility for my actions,” Ali said when asked by Assistant U.S Attorney Joe Thompson why she was pleading guilty in front of U.S She’s one of five people charged in the bribery attempt which made international news on the final day of closing arguments in the seven-week trial The juror immediately reported the incident to police and was excused from jury duty and the judge promptly sequestered the jury during deliberations for their safety Department of Agriculture programs that reimbursed schools nonprofits and child-care centers for feeding low-income children after school and during the summer The seven defendants were the first to be tried of the 70 people charged in the sprawling FBI investigation Prosecutors said more than $250 million in federal reimbursements was stolen and spent on luxury homes, cars and other lavish expenses in what was one of the largest pandemic-era fraud cases in the United States Said Farah and another defendant on trial were acquitted but Said Farah has been in custody since he was charged in the attempted bribe along with the three other men and the Farah brothers promised her $150,000 for her role in the attempted bribery of the youngest member of the jury and its only person of color The jurors’ names were not publicly disclosed during or since the seven-week trial; instead and Ali followed the woman from the courthouse as she drove home Ali confirmed to Thompson that she became concerned the plan to bribe the 23-year-old juror wouldn’t work and that she wouldn’t be paid she lied to Nur that she had met her at a bar and that the juror had demanded $500,000 Nur gave Ali $200,000 in cash to give the juror Thompson said Thursday that Ali wanted to steal the money but her plan was foiled when Abdulkarim Farah insisted on driving her to the juror’s house He removed the license plates on Ali’s rental car and recorded her delivering the cash Ali pocketed $80,000 and gave the juror’s relative a gift bag with the remaining $120,000 She used the juror’s first name even though it wasn’t publicly known who prosecutors said has returned to live in Minnesota from Seattle spoke loudly and clearly in court Thursday as she answered questions from Thompson and Doty After Thompson told her she could face nearly five to six years in prison declined to speak to reporters when they left the courtroom Prosecutors didn’t object to her remaining free until her sentencing hearing Ali was convicted in Scott County District Court of check forgery after she altered a $1,500 check from her company she spent three days in jail and was placed on supervised probation for two years including that the organization hadn’t demonstrated it was financially viable as required by federal rules Gar Gaar leaders took their case to the state Court of Appeals, arguing they were unfairly scrutinized, but the decision was upheld. In the meal fraud case, none of the 18 people who have pleaded guilty has been sentenced, but each could face prison terms running from about two years to nearly five years. Other defendants are scheduled to stand trial this fall or next year. Feeding Our Future executive director Aimee Bock, and defendants tied to Safari Restaurant in Minneapolis, the largest participant in the meal programs involved in the investigation, are scheduled for trial in February. Kelly Smith is a news editor, supervising a team of reporters covering Minnesota social services, transportation issues and higher education. She previously worked as a news reporter for 16 years. Ladan Hashemi receives funding from the New Zealand Ministry of Social Development and the UK Prevention Research Partnership grant (MR-VO49879/1) University of Auckland provides funding as a member of The Conversation AU University of Auckland, Waipapa Taumata Rau provides funding as a member of The Conversation NZ View all partners Children with traumatic experiences in their early lives have a higher risk of obesity. But as our new research shows this risk can be reduced through positive experiences Multiple adverse experiences were also prevalent with one in three children (32%) experiencing at least three traumatic events Childhood trauma includes a range of experiences such as physical and emotional abuse peer bullying and exposure to domestic violence separation or divorce and ethnic discrimination We found children from financially disadvantaged households and Māori and Pasifika had the highest prevalence of nearly all types of adverse experiences as well as higher overall numbers of adversities The consequences of these experiences were far-reaching Children who experienced at least one adverse event were twice as likely to be obese by age eight The risk increased with the number of traumatic experiences Children with four or more adverse experiences were nearly three times more likely to be obese certain traumatic experiences (including physical abuse and parental domestic violence) related more strongly to obesity than others This highlights the strong connection between early-life adversity and physical health outcomes This includes consuming excessive high-calorie “comfort” foods such as fast food and sugary drinks excessive screen time and physical inactivity children who experienced adverse events were more likely to adopt these unhealthy behaviours were associated with a higher risk of obesity Despite these challenges, our research also explored a promising area: the protective and mitigating effects of positive experiences mothers interacting well with their children children engaged in enriching experiences and activities such as visiting libraries or museums and participating in sports and community events children living in households with routines and rules children attending effective early childhood education Children with more positive experiences were significantly less likely to be obese by age eight those with five or six positive experiences were 60% less likely to be overweight or obese compared to children with zero or one positive experience Even two positive experiences reduced the likelihood by 25% Positive experiences can help mitigate the negative effects of childhood trauma But a minimum of four positive experiences was required to significantly counteract the impact of adverse events While nearly half (48%) of the study participants had at least four positive experiences a concerning proportion (more than one in ten children) reported zero or only one positive experience Traditional weight-loss programmes focused solely on changing behaviours are not enough to tackle childhood obesity we must also address the social environments life experiences and emotional scars of early trauma shaping children’s lives Fostering positive experiences is a vital part of this holistic approach These experiences not only help protect children from the harmful effects of adversity but also promote their overall physical and mental wellbeing This isn’t just about preventing obesity – it’s about giving children the foundation to thrive and reach their full potential schools and families all have a role to play healthy relationship initiatives and mental health services should be prioritised to support vulnerable families Trauma-informed care is crucial particularly for children from disadvantaged households who face higher levels of adversity and fewer positive experiences Trauma-informed approaches are especially crucial for addressing the effects of domestic violence and other adverse childhood experiences Comprehensive strategies should prioritise both safety and emotional healing by equipping families with tools to create safe nurturing environments and providing access to mental health services and community support initiatives participate in social networks and engage children in enriching activities Schools and early-childhood education providers also play a key role in fostering supportive environments that help children build resilience and recover from trauma Policymakers should invest in resources that promote positive experiences across communities addressing inequalities that leave some children more vulnerable than others we can counterbalance the impacts of trauma and help children lead healthier When positive experiences outweigh negative ones children have a far greater chance of thriving – physically This website is using a security service to protect itself from online attacks The action you just performed triggered the security solution There are several actions that could trigger this block including submitting a certain word or phrase You can email the site owner to let them know you were blocked Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page Ladan Ali pleaded guilty in the bribe case after she left a bag of $120,000 in cash at a juror’s home she was given new conditions of her release before her sentencing Ladan Ali, who dropped off a bag of $120,000 in cash to a juror in the federal Feeding Our Future trial last year in a shocking attempted bribe will stay out of prison until her sentencing after violating the conditions of her release of Fridley was given a lengthy list of additional conditions for her release — including remote electronic alcohol monitoring and completing an alcohol assessment or treatment program — at a hearing before U.S Ali pleaded guilty last September to bribery and is awaiting sentencing in that case She could face a possible sentence of nearly five to six years in prison According to charges filed in Hennepin County District Court last month 14 after she had rear-ended another car on Hwy she failed a field sobriety test and a breath test showed a blood alcohol content of 0.28% Micko indicated that Ali had already started a treatment program and there would be no additional hearings on the matter Attorney Kimberly Svendsen agreed with the conditions Jeff Day is a Hennepin County courts reporter. He previously worked as a sports reporter and editor. A woman accused of dropping a bag of cash at the home of a juror in the Feeding Our Future case has entered a guilty plea Ladan Ali pleaded guilty in federal court on Thursday to bribery of a juror She also faced counts of conspiracy to bribe a juror and corruptly influencing a juror She initially entered a “not guilty” plea on June 27 Prosecutors say Ali surveilled Juror 52 in the Feeding Our Future trial, before showing up at her home with a bag containing $120,000 in cash. Four others were charged with conspiracy to bribe a juror bribery of a juror and corruptly influencing a juror in connection with the bribery scheme: Abdiaziz Farah was additionally charged with obstruction of justice. Nur pleaded guilty in July. You can find more of KSTP’s reporting on the Feeding Our Future case here. Ladan Rafii is an expert on international humanitarian law and political affairs who has worked for the United Nations (UN) the Organization for Security and Cooperation in Europe and humanitarian non-governmental organizations Translations may contain inaccuracies—please refer to the original content Like many people around the world, I was stunned by what I saw on the night of Thursday, June 27, when President Joe Biden went up against Donald Trump as others have referred to it as a debacle national embarrassment (and that's without using any of the expletives) It's also difficult to consider it "presidential" after what we witnessed between the two candidates What stuns me more than anything else is how others let this happen Advisers are there to advise—and close advisers are expected to know you better than anyone else because they spend time with you and see you more than others they are the ones you let into your professional world—and often personal life—more than outsiders there's an element of trust and understanding that fosters a sense of collaboration and cooperation at the highest possible levels If you surround yourself with the wrong ones If you surround yourself with some of the best you're likely to get the best from them too When it comes to Biden, the only close adviser I once knew is his former White House chief of staff and trusted confidant, Ron Klain I attended Georgetown University with him many years ago so we were in a small classroom sitting in close proximity to one another he was impressive because of his appearance: An Adonis who was physically perfect in every way I would often wonder how God made someone so handsome I was impressed (if not amazed) by his level of intellect he revealed this to us—without any arrogance but with a measure of confidence that made us all take note of him Every time our professor asked a question and none of us knew the answer (or even had a clue what he was getting at) Ron's hand would be the only one that went up because the rest of us had no idea how he did it Which is why I'm having such difficulty believing and processing what happened just a few nights ago I learned from a New York Times report that Ron left the White House last year to become chief legal officer of Airbnb I thought maybe he no longer wanted to be associated with what he perceived to be a sinking ship Anyone as clever as him would certainly know when he's on board one and take the right measures to make sure he jumps off it when the first signs appear and the ship begins to teeter and help prepare Biden for his debate with Trump circles for being one of the best debate trainers in town He's very sharp and astute with a depth of political knowledge and experience very few can match That same article claimed he "was critical to Mr Biden's debate preparations during the 2020 campaign." Here's some of what Ron said that was quoted there: "I think what we have to see is something different than we saw in 2016 and 2020 where the debate commission lost control of the debates "We need to have debates where the candidates get equal time .. where the American people can compare the two people who are the leading candidates for president." Maybe more than you would have ever wanted or known These days I often ask myself: What happened to the Ron Klain I once knew How could he have let such a calamity happen on live television in front of a global audience of tens of millions With all that's at stake both at home and around the world We want to know the answers—the world wants to know them—and we need them now Do you have a unique experience or personal story to share? See our Reader Submissions Guide and then email the My Turn team at myturn@newsweek.com EDT: An incorrect reference to Ron Klain's Georgetown school was removed Newsweek is committed to challenging conventional wisdom and finding connections in the search for common ground Newsletters in your inbox See all A significant correlation was observed between IPGEslope and speech perception in both quiet and noise for between-subject data especially when the relative importance of frequency bands was considered. A strong and significant correlation was also observed between IPGEslope and age when stimulation was performed with cathodic-leading pulses but not for the anodic-leading pulse condition. Based on the outcome of this study it can be concluded that IPGEslope has potential as a relevant clinical measure indicative of cochlear health and its relationship to speech intelligibility. The polarity of the stimulating pulse could influence the diagnostic potential of IPGEslope. Volume 17 - 2023 | https://doi.org/10.3389/fnint.2023.1125712 This article is part of the Research TopicNeural Interfaces for Sensory InputView all 8 articles Background: One factor which influences the speech intelligibility of cochlear implant (CI) users is the number and the extent of the functionality of spiral ganglion neurons (SGNs) referred to as “cochlear health.” To explain the interindividual variability in speech perception of CI users a clinically applicable estimate of cochlear health could be insightful The change in the slope of the electrically evoked compound action potentials (eCAP) amplitude growth function (AGF) as a response to increased interphase gap (IPG) (IPGEslope) has been introduced as a potential measure of cochlear health Although this measure has been widely used in research its relationship to other parameters requires further investigation Methods: This study investigated the relationship between IPGEslope demographics and speech intelligibility by (1) considering the relative importance of each frequency band to speech perception and (2) investigating the effect of the stimulus polarity of the stimulating pulse The eCAPs were measured in three different conditions: (1) Forward masking with anodic-leading (FMA) pulse (2) Forward masking with cathodic-leading (FMC) pulse This allowed the investigation of the effect of polarity on the diagnosis of cochlear health For an accurate investigation of the correlation between IPGEslope and speech intelligibility a weighting function was applied to the measured IPGEslopes on each electrode in the array to consider the relative importance of each frequency band for speech perception A weighted Pearson correlation analysis was also applied to compensate for the effect of missing data by giving higher weights to the ears with more successful IPGEslope measurements Results: A significant correlation was observed between IPGEslope and speech perception in both quiet and noise for between-subject data especially when the relative importance of frequency bands was considered A strong and significant correlation was also observed between IPGEslope and age when stimulation was performed with cathodic-leading pulses but not for the anodic-leading pulse condition Conclusion: Based on the outcome of this study it can be concluded that IPGEslope has potential as a relevant clinical measure indicative of cochlear health and its relationship to speech intelligibility The polarity of the stimulating pulse could influence the diagnostic potential of IPGEslope Cochlear implants (CIs) are the treatment of choice to restore hearing in patients with severe to profound hearing loss (HL) The success of the treatment depends on individual factors such as the cognitive abilities of the patient or the reaction of the immune system to the implant as well as on implant type and the depth of insertion of the electrode array One influential factor is the condition of the cochlea –Specifically the survival and the physiological status of the spiral ganglion neurons (SGN) Although the importance of this factor is clear Spiral ganglion neurons are the target neurons for electrical stimulation with cochlear implants. Large variations have been documented in the number and condition of surviving SGNs in CI recipients, and this could contribute to the similarly large variability in auditory performance observed (Seyyedi et al., 2014) The parameters describing the status of the auditory nerve include the number of SGNs (neural count) and myelination of their peripheral processes (PP) we will use “cochlear health” as a generally inclusive term to encompass all of these parameters In a within-subject comparison of left and right ears eliminating any between-subject confounding factors the number of SGNs was consistently higher in the ear which produced the better word recognition scores Despite the positive correlation observed between cochlear health and auditory performance in CI users several of the limitations of previous studies were also present here histological data were again pooled across the cochlea although only for the sub-group of participants with short electrode arrays and latency in implanted normal-hearing (NH) and pharmaceutically deafened guinea pigs to investigate the consequences of secondary degeneration of SGNs after severe hair cell loss through chemical ablation A significant correlation between spiral ganglion cell packing density and the IPGE on some of the AGF characteristics Illustration of the methods employed to calculate IPGEslope (A) and IPGEoffset (B) The eCAP AGFs obtained by IPG 2.1 and 30 μs are plotted in black and gray the green lines mark the AGFs steepest slopes the green horizontal lines indicate the offset between the AGFs with short and long IPGs for several N1-P2 amplitudes The contradictory conclusions of the two above-mentioned studies emphasized on the necessity of further research to clarify the suitability of each measure for estimation of cochlear health Speech information in different frequency bands, transmitted from different sections of the cochlea to the brain, is not of equal importance (ANSI, 1997) two ears with the same ASM of the IPGE on eCAP characteristics may differ in speech perception if the distribution of surviving SGNs differs between each cochlea Regardless of the type of cochlear health measure when it comes to relating the measure to speech recognition performance any such measure may benefit from an adjustment using a band importance function that reflects the human auditory system mechanisms of speech perception which focused on the average differences of the responses to anodic-leading and cathodic-leading stimuli both polarities are investigated separately in the current study to examine the sensitivity of each polarity separately for use as an electrophysiological biomarker for SGN degeneration the goals of this study were to investigate the relationship between IPGEslope and speech intelligibility in CI users by (1) by investigating the effect of the polarity of the stimulating pulse and (2) considering the band importance weighting function when investigating the correlation between the speech perception measures and IPGEslope within the study and 13 suffered from progressive hearing impairment which was detected prelingually Subjects 7 and 13 had restricted speech development and were diagnosed with mild auditory dyslalia Electrode 12 of the right ear of subject 12 and electrodes 4 and 5 of the left ear of subject 7 were deactivated clinically and 10 was interrupted due to the subject’s complaint of an unpleasant sensation The left ear of subject seven was the only ear implanted with a relatively short electrode array (Flex24 EAS) Recruitment of subjects for this study was approved by the Ethics Committee of the Goethe University Hospital in Frankfurt (ERB number 44/19) and all subjects gave written informed consent Subjects received an expense allowance for participation in the study Demographic data and summary statistics are provided for age duration of hearing loss until CI-implantation The measurements were performed separately for the two ears removing the audio processor from the contralateral side using the clinically adjusted audio processor configurations (i.e. threshold and most-comfortable loudness levels and compression) The microphone directional sensitivity was set to “omnidirectional” and noise reduction and automatic functions were disabled to create a uniform testing condition between the users For each measurement two of the lists were randomly selected The words were presented to the listeners at 65 dB SPL in quiet The listeners were instructed to repeat the words The percent of words repeated correctly was recorded Test results of the two presented lists were averaged the across site mean (ASM) of the weighted IPGEslope was calculated These ear-specific weighted IPGE ASMs were then used to investigate the correlation between these measures of cochlear health and the two speech perception measures Figure 2. One-third octave band importance function for monosyllables of speech in presence of noise (Supplementary Table 2 ANSI S3.5 1997) in blue and adapted to MED-EL default filter bank setting in red Electrode impedances were measured via impedance field telemetry (IFT) using the clinical software (MAESTRO 7.0 Austria) with the MAX Programming Interface (MED-EL Medical Electronics This results in measurements of the implant’s supply voltage and the impedance values of the 12 implanted electrode contacts the measurement results were exported (using the scientific export) from the clinical software into XML files and the supply voltage and the electrode impedance values were extracted for determining the compliance limits The extracted values were also used in the statistical analysis of the results United States) research software was used to perform loudness-based measurements with pulse-forms and sequences identical to those used in the following experimental measurements The MATLAB program communicated with the implant using the Research Interface Box 2 (RIB2) Dynamic Link Library (dll) 64 bit (Department of Ion Physics and Applied Physics the MAX Programming Interface and a suitable coil Threshold (THR) and maximum acceptable level (MAL) stimulation charges were measured using manual control for all active electrodes using cathodic-leading biphasic stimuli with IPG of 2.1 μs in sequences of at least 400 ms duration to allow sufficient loudness integration The phase duration was the same as that selected for the following eCAP measurements The amplitude could be increased up to the compliance level which was calculated after impedance measurement A custom-made MATLAB-based tool was used for eCAP measurements considering the THR and MAL values from the loudness fitting tool The communication with the implant was the same as the software for the loudness-based measurement FM artifact reduction allows investigation of the auditory nerve response to pulses with a specific initial polarity all eCAPs were measured both with anodic-leading (FMA) and with cathodic-leading (FMC) pulses in order to investigate the polarity-specific behavior of neural responses An AP artifact reduction method was implemented by averaging the FMA and FMC probe responses It should be noted that FMA and FMC probes were not measured consecutively which is different to how AP is implemented in clinical software The combination of polarities and IPGs resulted in six different conditions: FMA 2.1 ECAP recordings were performed in monopolar configuration at a rate of approximately 60 Hz using the standard stimulation ground of the implant Recording electrodes were by default set to the next more apical active electrode relative to the stimulating electrode (n−1 except for electrode 1 (the most apical electrode) which had electrode 2 as the default recording electrode the location of each recording electrode could be altered by the investigator to yield a clear eCAP based on visual inspection following an initial test pulse The recording electrode was neighboring the stimulating electrode in nearly all cases ECAP recordings were obtained with high temporal resolution (stimulator internal sampling rate 1.2 MHz) The measurement delay was set to 120 μs for stimuli with IPG = 2.1 μs and to 149 μs for stimuli with IPG = 30 μs to compensate for the different durations of the respective biphasic stimuli Both masker and probe signals were measured with the same recording electrode pair The masker level was 10% higher than that of the probe for which the masker was set to MAL and the probe was set to 95% of MAL This procedure led to a smaller increase for the last stimulus step in the AGF and to potentially less effective masking The default phase duration was set to 30 μs and the default masker-probe interval to 350 μs but both parameters could be adjusted by the investigator when necessary For subjects 7 and 10 the phase duration was increased to 40 and 50 μs to record eCAPs with sufficient reliability Subject 14 had different phase durations in right (30 μs) and left (50 μs) ears AGFs were recorded on all active electrodes with 10 amplitude steps between and including threshold and MAL This resulted in a total of 576 eCAPs for each ear in the case of 12 clinically active electrodes To further reduce the influence of the measurement noise the recorded eCAPs were filtered with a fifth-order Butterworth lowpass filter having a cut-off frequency of 5 KHz which effectively doubled the filter order to ten biasing the determination of eCAP characteristics a weighted linear least-square analysis was applied to the eCAP Each eCAP trace was divided into three equally long parts and samples within the first second and third part were multiplied with weights of 0.1 to emphasize the tail of the response in the estimation of the trend where the presence of the artifact is more pronounced This allowed more accurate estimation of the trend This estimated trend was then subtracted from the eCAP in order to eliminate the artifact caused by internal circuitry the response to the lowest subthreshold current level was subtracted from the detrended eCAP the N1 peak was defined arbitrarily as the amplitude of the signal at 0.03 ms after stimulus onset the above-mentioned time interval was expanded toward the onset of the signal to compensate for the delay in the recording and to allow the detection of any peaks that occurred earlier than expected the N1-P2 peak amplitude difference as a function of stimulating current level each polarity and each artifact reduction approach (FM/AP) An automatic AGF selection was performed in order to only estimate AGFs with adequate reliability The criteria for AGF selection were based on the maximum eCAP amplitude (the N1-P2 peak-amplitude for highest current level must be larger than 120 μV) impedance of the stimulating electrode (must be lower than 10 kΩ) monotonicity of the AGF and the comparison between the maximal AGF slope and the slope of a line fitted to the first three points of the AGFs (the response to the subthreshold and threshold currents) as an estimation of the artifact the slope difference should be larger than 0.5 (μV/ μA) unless the slope of the line fitted to the eCAP amplitude measured with subthreshold and threshold currents was smaller than 0.3 (μV/ μA) Single and multiple linear regressions were employed to investigate the relationship between the IPGEslope and speech test outcomes The coefficient of determination (R2) was calculated based on the Pearson correlation coefficients in each case These were reported together with the corresponding level of significance In the case of multiple linear regression adjusted R2 was reported to compensate for the effect of over-fitting caused by the moderate sample size of this study Where n and k were the sample size and number of independent variables a weighted Pearson correlation analysis was also implemented to account for missing data due to rejected AGFs the cases that the criteria for an automatic selection of AGF by the algorithm were not satisfied The correlation coefficient was calculated according to Where xi and yi were samples of the independent and dependent variables of length n and x̄ and ȳ were the corresponding mean values In cases where each sample was an ear (in case of analysis of monaural data) was the number of electrodes with accepted AGF for both IPG 2.1 μs and IPG 30 μs divided by the total number of electrodes (12) For the analysis of the ear-differences data was the average of the weights for each ear of the subject in case of subject 4 and for FMA condition an acceptable AGF was obtained for both employed IPGs on 10 and 2 electrodes on the right and left ears resulting in weights of 0.8333 and 0.1667 for these ears a weight of 0.5 (average of 0.8333 and 0.1667) was therefore applied In the context of weighted Pearson correlation to calculate the corresponding level of significance the test value for the Student’s t-distribution was defined as nw was the effective sample size and was defined as the exponent of the entropy of the weights with weights being normalized to their summed value The corresponding level of significance (p-value) to the adapted t-value in Eq (3) was calculated using MATLAB’s default numerical methods as for the standard p-value To identify outliers for the variables age duration of hearing loss until implantation (DHL) hearing aid experience (HAE) and CI experience (CIE) The coefficients of determination for the ranges 0.0–0.3 and 0.6–1.0 were categorized as weak Table 1 contains subject demographic data. Subjects 9 and 16 were the youngest and oldest participants of this study. Six subjects had residual hearing. The extent of residual hearing was comparable among this subgroup. Subject 7L was the only case of implantation with a short electrode array (Table 1) This subject had the longest duration of HL and the CI experience was below the mean value of the group data No residual hearing was observed for this subject at the time of experiment Subject 2 was the only subject who showed no ear-difference in any of the investigated demographic data (duration of HL This subject was implanted with the same electrode array type and wore the same type of speech processor on both sides the variation in electrode array type was low among the ears tested Most of the ears were implanted with a 28 mm long electrode array There was a small difference in electrode length in a few subjects hearing aid experience and CI experience were the same because there was no ear-difference in the onset of HL and hearing aid use in any subject the time of implantation was the only cause of variation in all these three demographic data for the ear-differences (A) Depicts the speech reception thresholds (SRT dB SNR) measured for the German matrix sentence test for the right ear (red bars) left ear (blue bars) and the absolute value of the ear-differences (right-left black bars) sorted according to the SRT for the best ear in descending (improvement in speech intelligibility) order (B) Displays the outcome of the Freiburg monosyllable test (% correct) The subjects order and the display are the same as (A) weak but significant correlations were found between monaural SRTs and demographic data of type age (R2 = 0.20*) and CI experience (R2 = 0.21*) Figure 4. The correlation between the two speech intelligibility measures i.e., speech reception threshold (SRT) and Freiburg monosyllable test scores (FMT scores) for the monaural data (left panel) and the ear-differences (right panel). Each subject is represented by a number according to Tables 1, 2 blue and black indicate data from right ear Black solid lines indicate significant correlations Dashed gray regression line indicate non-significant correlations ***p-value ≤ 0.001 Figure 5 shows the measured IPGEslope for all the subjects Each subfigure shows the calculated IPGEslope for individual electrodes (Electrode 1: the most apical Electrode 12: the most basal) and their corresponding ASM for one ear The right and left ears are indicated with red and blue squares and triangles mark the three conditions FMA Black crosses indicate clinically deactivated electrodes The calculated IPG effect on slope (IPGEslope) for each of the 12 electrodes (1: most apical and 12: most basal) and their corresponding across site mean (ASM) values The data from right (B) and left (A) ears are coded in red and blue and triangles mark forward masking with anodic-leading pulse (FMA) forward masking with cathodic-leading pulse (FMC) and alternating polarity (AP) conditions Crosses indicate the clinically deactivated electrodes Arrows indicate IPGEslope with magnitudes larger than 40 (μV/ nC) For two out of the three conditions for each electrode the data points are slightly shifted to the left and right to improve visibility An exemplary case of a successful measurement is subject 16 For subject 16L an acceptable monotonic AGF was obtained for all electrodes and both polarities of the stimulating pulse Subject 5 is an example for incomplete measurements successful eCAP measurements were obtained for only four electrodes The calculated IPGEslope values for these electrodes were relatively low across the electrodes A clear variation in IPGEslope along the cochlea was observed in subject 2L with electrode 2 and 9 (examples of higher IPGEslope values) in contrast to electrode 4 and 11 exemplary cases that result in lower IPGEslope values For some of the subjects such as subject 9 a large difference was observed between the right and left ears in terms of the number of electrodes for which IPGEslope was available For subject 9L (who had a congenital component to their HL) successful measurements were obtained for all the three conditions for most of the electrodes For the three conditions further differences were observed between the ears the difference in IPGEslope between conditions was minor a difference between polarities was apparent in the estimated IPGEslope measurements were successful for most of the electrodes in contrast to FMC which resulted in successful measurements on only 2 electrodes A noticeable difference was also observed between FMA and AP for the estimated IPGEslope Subject 7L and subject 9R were excluded from all analyses due to the extent of the missing data for these ears Both subjects had a congenital component to their HL data of subject 7 and 9 was excluded for both ears since calculation of ear-differences was not possible A comparison of IPGEslope measured in this study with the ones measured in a guinea pig model (Figure 7 of Ramekers et al., 2014) showed a smaller magnitude of this cochlear health measure for human subjects. For the 6-week deafened animals in the study of Ramekers et al. (2014) which are comparable to the human subjects of this study in terms of the degree of HL the measured IPGEslope was 6 to 8 (depending on the phase duration) times larger than those measured in this study for AP condition Figure 6 shows a scatter plot of the SRT as a function of IPGEslope ASM for the three conditions (FMA The upper panel shows the standard Pearson correlation results In this condition all ears contributed equally to the obtained coefficient of determination regardless of the extent of missing electrode data The middle panel shows the weighted Pearson correlation The size of the number labels representing individual ears was scaled according to the corresponding weight for that ear e.g. the subject 16L has the largest label because eCAPs were measured successfully for all 12 electrodes subject 10L with successful eCAP measurement on only three electrodes has one of the smallest labels The difference in the print size of each number in panels (B,C) is proportional to the number of electrodes with successful eCAP AGF measurement for that ear the weighting function was applied to the measured IPGEslope on individual electrodes before calculation of ASM of each ear in order to take into account the relative contribution of each electrode’s assigned frequency band to speech intelligibility a weighted Pearson correlation was calculated No correlation was observed between IPGEslope and SRT when the effect of missing data was not compensated for and when the relative importance of frequency bands was not taken into account (upper panel) a weighted Pearson analysis resulted in a weak but significant correlation (middle panel) for both polarities (FMA and FMC) the highest correlation was observed when the effect of missing data was compensated and the relative importance of frequency bands for speech intelligibility was considered (FMA: Rw2 = 0.25* this observation resulted in a trend but showed no significant correlation (lower panel) For the subset of the ears with more successful measurements the magnitude of the coefficient of determination was comparable between the three conditions (FMA: R2 = 0.55* The standard Pearson correlation between speech reception thresholds (SRT) and weighted IPGEslope ASM for monaural data Only the ears with successful eCAP AGF measurement on at least eight electrodes in all the three conditions (A: FMA Right and left ears are plotted in red and blue No significant correlation was observed between ear-differences of SRT and ear-differences of IPGEslope either for the standard (FMA: R2 = 0.06 AP: R2 = 0.04) or the weighted (FMA: Rw2 = 0.06 AP: Rw2 = 0.04) Pearson correlation analyses Applying the weighting to IPGEslope to account for the relative importance of each frequency band for speech intelligibility did not result in a significant correlation with SRT (FMA: Rw2 = 0.06 AP: Rw2 = 0.13) when ear-differences were analyzed (data not shown) Figure 8 depicts the FMT scores as a function of the IPGEslope for monaural data and has the same structure as Figure 6 A weak but significant correlation was observed between monaural FMT scores and monaural IPGEslope ASM for FMC as well as for the standard Pearson correlation analysis and in the absence of applying the weighting to account for the relative importance of each band for speech intelligibility The magnitude of the coefficient of determination was improved when the weighted Pearson correlation analysis was employed the speech-related weighting was also applied although the correlation was not significant in case of AP (FMA: Rw2 = 0.28* No significant correlation was obtained between IPGEslope ASM and FMT scores either for standard or Pearson correlation or after applying the speech-related weighting when ear-differences were analyzed (FMA: Rw2 = 0.18 Figure 9 depicts age as a function of IPGEslope for the three artifact reduction methods with monaural data The correlation analysis showed a clear effect of the polarity of the stimulating pulse: a significant correlation was observed only when a cathodic-leading pulse was used for stimulation The strength of the correlation (R2 = 0.38 R = −0.62) for the AP condition was intermediate between those obtained with FMA and FMC No correlations were observed between hearing aid experience duration of HL or CI experience and the IPGEslope (data not shown) Figure 9. The correlation between IPGEslope ASM and age for monaural data. Each column represents one artifact reduction approach (A: FMA, B: FMC, C: AP). Each number represents one ear which is in accordance with Table 1 The right and left ears are plotted in red and blue The difference in the print size of each number is proportional to the number of electrodes with successful measurement for that ear Figure 10 shows the correlation between IPGEslope and age only for the subset of ears with relatively successful eCAP measurement on at least 8 out of the 12 electrodes This strict inclusion criterion (applied post hoc) strengthened the correlations between the two parameters for all the three artifact reduction approaches a strong and highly significant correlation (R2 = 0.84 R = −0.91) was observed which was considerably higher than the correlations observed in FMA and AP (R2 = 0.60 Figure 10. Standard Pearson correlation analysis between age and IPGEslope ASM for monaural data. Each column represents one of the three conditions investigated (A: FMA, B: FMC, C: AP). Only the ears with successful eCAP measurement on at least eight electrodes in all the three conditions are included. Right and left ears are plotted in red and blue, respectively. Each number represents one ear which is in accordance with Table 1 A multiple linear regression model was used to investigate the relation of cochlear health measures to demographic data and to electrode impedances The model was also used to investigate whether considering demographic data and classical impedances in addition to cochlear health explains the variation in speech intelligibility to a greater extent The obtained results for the multiple linear analysis were compared to the standard Pearson correlation in a two-dimensional domain as the reference point The choice of standard instead of weighted Pearson correlation here was to avoid implementation of weighted multiple regression analysis which requires complex calculations four- and five-dimensional models were used adjusted coefficients of determination (Radj2) were reported to compensate for overfitting resulting from an increase in dimensionality The analysis showed that only age was a significant predictor of IPGEslope for FMC and AP conditions Addition of other investigated demographic factors or electrode impedances did not result in an improvement of model prediction Table 2 describes the variations in SRT as a function of the cochlear health measure alone (first row) and together with CI experience more than 50% of the variation in SRT was explained in the case of FMC Considering both CI experience and IPGEslope significantly improved the model prediction in comparison with considering only IPGEslope as the independant variable [df(1,19) the highest explained variation was almost 30% Results from the multiple linear regression models to predict the variation in speech reception thresholds (SRTs) To compare IPGEslope with IPGEoffset, the same analysis introduced by Brochier et al. (2021) was applied to the human data of this study. Two step-sizes for the sampling of N1-P2 amplitudes were used, 0.1 μV as introduced by Brochier et al. (2021) and a step-size of 0.02 μV. Figure 11 shows the results and has the same structure as Figure 6 It depicts SRTs as a function of IPGEoffset for standard (upper panel) and weighted (middle panel) Pearson correlation and as a function of weighted IPGEoffset for weighted Pearson correlation (lower panel) to consider both the effect of missing data and relative importance of each frequency band for speech intelligibility No significant correlation was observed in any case regardless of the employed step-size Figure 11. The correlation between speech reception threshold (SRT) and IPGEoffset ASM for monaural data. The figure has the same structure as Figure 6 demographic data and the impact of the application of a weighting function related to the speech band importance function on a measure of cochlear health were all investigated No correlation was observed for ear-differences in any condition the difference of the means of AGF slopes for single IPGs was reported (most probably to overcome the ambiguities raised by missing data) The two approaches would have been identical in the absence of missing data for some of the electrodes no AGF was obtained at least for one of the IPGs resulting in a difference when changing the order of averaging and subtraction transferring the approach of analysis of ear-differences to a random selection of bilateral CI users might not always yield a useful result Many studies have investigated the proper unit for analysis of psychophysical and physiological measurements in CI users. McKay (2012) investigated the psychometric probe threshold measured using a forward masking paradigm The author argued that the ratio or logarithmic units are the best for estimation of probe thresholds because only in these domains are the effects of electrode-neuron distances canceled out and only the effective change that neurons experience remains increasing the stimulation current from 100 to 200 μA might result in an increase of 0.5–1 μA in one case and from 1 to 2 μA in other case In both cases the effective current received by neurons was doubled as a response to doubling the stimulation current but there is a difference in the raw increment The author argued that the ratio and logarithmic domain can reflect this effect but not the linear domain Brochier et al. (2021) used the same argumentation for the calculation of IPGEoffset and applied the IPGEoffset in the logarithmic domain as a cochlear health measure robust against non-neural factors such as variation in electrode-neuron interfaces or variation in the stimulating current level It should be noted that as IPGEoffset is a differential measure a logarithmic transformation not only compensates for different field gradient strengths effect current at the recruited population Degeneration affects the degree of the temporal integration of neurons a reliable estimation of cochlear health requires a measure which should be sensitive to changes in temporal integration This argumentation was confirmed with the outcome of this study which showed a significant correlation between IPGEslope in the linear domain and speech test outcome but no significant correlation for IPGEoffset in the logarithmic domain The observation that the IPGE in the linear domain showed only a significant effect could therefore be explained by differences in how the neural population could integrate over time and that this information is removed by an analysis in the logarithmic domain The findings of this study are in line with the study of Takanen et al. (2022) who modeled three cochlear health measures and (3) IPGEoffset in the logarithmic domain They investigated the effect of electrode-neuron interfaces and cochlear health (defined as the number of surviving SGN) They reported that only IPGEslope in linear domain was sensitive to cochlear health although it was also affected by variation in electrode-neuron distance Relative IPGEslope and IPGEoffset in logarithmic domain were not sensitive to either factor The relatively small sample size in such studies is always a statistical obstacle when attempting to generalize and compare results the current investigation differs from the previous studies in various factors such as the focus on cathodic-leading stimuli (in contrast to anodic minus cathodic investigation of individual subjects (in contrast to averaging across all or groups of subjects) and investigating the IPGE between 30 and 2.1 μs for different polarities (in contrast to comparisons between polarity effect on eCAP threshold as well as a different subject selection may be used to argue for the more conclusive results in this study Setting the shorter IPG to 2.1 μs was suited to have samples of the second phase interrupting the vulnerable period longer IPGs may not be suited for the choice as the shorter IPG The etiology of HL was progressive in 10 of 13 subjects (77%) in this study suggesting ongoing degenerative processes as well as the presence of remaining hair cells and PPs Further research is required for more detailed investigation of the principles underlying preferential polarity sensitivity in CI users Although a significant correlation was observed between cochlear health and speech measures variations in speech perception among CI users are still large In order to explain the interindividual variability in speech perception of CI users more than one factor needs to be taken into account a multiple linear regression model was employed and the variation in speech intelligibility was partly explained IPGEslope was used as the main independent variable Integration of CI experience in the model in addition to IPGEslope resulted in the greatest performance of the model This is most probably because IPGEslope was correlated to age and inclusion of age therefore did not provide complementary information to the model the observed correlation was most likely due to CI experience It is important to consider the effect of overfitting with high dimensional models particularly in cases of a smaller sample size as in the one employed here Adjusted R2 values were reported to compensate for the effect of overfitting caution should be taken in interpreting the outcome of these models in particular with respect to the data size of 24 ears it is suggested to repeat this analysis with a larger dataset and (if possible) with less missing data it was not possible to include only the ears with relatively complete eCAP measurements based on the higher correlation observed in case of considering only ears with successful measurements on at least 8 electrodes it can be concluded that employing such a model with a dataset with less missing data might result in an increase in the predictive performance of the model which might have an increased contribution from overfitting For future studies additional factors such as deficits in the fitting of CI processors or issues related to rehabilitation measures may be of interest In this study to assess the performance of IPGEslope in the estimation of cochlear health (neural status) the correlation with speech intelligibility was selected The study design controlled for many of the covarying factors affecting speech intelligibility The variability in electrode array type was kept as low as possible to completely factor out the interindividual variability in reconstruction of cochlear tonotopy the information about the length of electrode array should be assessed together with the respective insertion angle and cochlear size this information should be considered in future In an attempt to control for the cognitive ability of the subjects ear-differences in cochlear health measures and speech intelligibility were employed analysis of the ear-differences revealed limitations to this approach These limitations include the difficulty in recruiting a large enough number of subjects with between-ear SRT differences higher than 1 dB SNR and the difficulty of obtaining complete eCAP measurements for both ears in some subjects the analysis of monaural data was preferred in the present study this approach came at the expense of losing control over the cognitive ability (which is a highly individual variable and demonstrated in many studies to be related to performance) it might be useful for future studies to assess the cognitive ability of the subjects via additional testing in order to describe some of the remaining unexplained variation in speech intelligibility of the CI users Considering the variation in the spread of excitation might help to better explain the outcome of this study the relationship between electrode impedances and cochlear health should be investigated to assess the impact of electrode impedances on cochlear health measures charge integration efficacy might be a faster measure of cochlear health as it can be measured psychophysically in a co-operative subject its subjective nature might restrict its possible application e.g. Further studies are required to compare IPGEslope and charge integration efficacy in terms of their accuracy as well as their vulnerability to missing data For any application of band importance function it is desirable to consider as many of these factors as possible to obtain a function which is tailored to that particular application It is hypothesized that a tailored band importance function together with complete electrophysiological measurement results in a more accurate prediction of speech intelligibility The clinical map of some of the subjects might be different than the default map Various factors determine the suitable fitting map for individual users in terms of the filter bank setting The presence of low frequency hearing usually results in a change in the filter bank setting because in such a case the listeners are able to hear the low frequencies acoustically and the CI codes a restricted frequency bandwidth Another influential factor might be the usage of the anatomy-based fitting which aims at preserving the natural frequency-place map the amount of the change depends on the insertion depth and the position of the electrodes in the cochlea Electrode deactivation also affect the filter bank setting and consequently the band importance function open or short circuitry are exemplary common reasons for electrode deactivation which results in the frequency redistribution among the remaining electrodes and depends on the number of deactivated electrodes The extent of the variation from the default map is individual and ranges from a slight change to a moderate one Employment of band importance functions adapted to individual maps of the CI users is worthwhile to be tested in future This study investigated the applicability of cochlear health measures for prediction of speech perception capabilities in CI users We focused particularly on investigating the effect of the polarity of the stimulating pulse and the utility of the band importance function significant correlations were observed between IPGEslope and speech perception outcomes with equal correlation strength for anodic-leading and cathodic-leading pulses We found that reliable relationships between the investigated parameters of cochlear health could only be established when the relative importance of each frequency band for speech intelligibility was taken into account A significant negative correlation was observed between IPGEslope and age cathodic-leading pulses resulted in a significant and strong correlation while anodic-leading pulse showed no significant correlation supporting the hypothesis that cathodic-leading pulses are better suited for detection of degenerated SGN PPs The higher sensitivity of younger CI users to cathodic-leading may be due to a larger number of excitable PPs in regions closer to the electrode contact where a cathodic stimulus leads to depolarization more effectively Missing data was particularly detrimental to the analysis The highest correlations were observed when the effect of missing data was compensated either by implementation of a weighted correlation or when only ears with relatively complete measurements were included into the analysis For an accurate estimation of cochlear health (neural status) measurements of high quality eCAPs were essential Stimulation with a cathodic-leading phase might help to improve the estimation of cochlear health The results of this study together with further information about current spread which is assumed to be an individual factor and degrades the spectral resolution of the coded speech have the potential to explain the observed variation in performance achieved by CI users partly due to variation in the degeneration level of the auditory periphery The raw data supporting the conclusions of this article will be made available by the authors The studies involving human participants were reviewed and approved by the Ethics Committee of the Goethe University Hospital in Frankfurt (ERB number 44/19) The patients/participants provided their written informed consent to participate in this study LZ wrote the manuscript and analyzed the data BM analyzed the data and created the figures HB and UB designed the study and revised and finalized the manuscript JT reviewed the study design and the manuscript CG designed the study and revised the manuscript All authors contributed to the article and approved the submitted version Support for this work was provided in part by MED-EL GmbH We thank Marko Takanen for his helpful consultation on speech information Philipp Spitzer for his substantial support with eCAP signal processing Darshan Shah for creating the custom-made MATLAB research tool two students Vera Komeyer and Sophie Hamkens for data measurement and Konrad Schwarz for their constructive feedback and the review of an early version of the manuscript and Patrick Connolly for providing English language editing for the manuscript We would like to express gratitude to the participants of the study for the generous dedication of their time A portion of this work was presented at the 2021 Conference on Implantable Auditory Prostheses The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this 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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) distribution or reproduction in other forums is permitted provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited in accordance with accepted academic practice distribution or reproduction is permitted which does not comply with these terms *Correspondence: Uwe Baumann, VXdlLkJhdW1hbm5Aa2d1LmRl Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish the woman that prosecutors allege was part of a plot to bribe a juror in the “Feeding our Future” trial faced a judge on Thursday afternoon in St Thirty-one-year-old Ladan Mohamed Ali entered “not guilty” pleas to the charges filed against her bribery of a juror and corruptly influencing a juror said his client had “no comment” on the charges as they left court On Wednesday, U.S. Attorney Andrew Luger announced charges against five people who they allege were part of the bribery plot “These defendants engaged in a chilling attack on our justice system,” Luger said during Wednesday’s news conference Luger mentioned considering using possible anonymous juries in cases down the road to try and protect jurors from outside influence where the identities of the jurors are withheld from prosecutors “It comes with some price though,” said retired Hennepin County District Court Judge Kevin Burke about using anonymous juries and the message it sends to the juror “It creates an atmosphere in which you say with these defendants are dangerous and we need to protect you; how do you presume somebody innocent if that’s the message?” Burke said But the retired judge said it’s an option prosecutors could use in certain situations “It’s just one that you’d use quite rarely,” Burke added Prosecutors alleged the “Feeding our Future” cases are part of the country’s largest COVID-19 related fraud cases Earlier this month Numerous studies have highlighted cognitive benefits in lifelong bilinguals during aging, manifesting as superior performance on cognitive tasks compared to monolingual counterparts. Yet, the cognitive impacts of acquiring a new language in older adulthood remain unexplored. In this study, we assessed both behavioral and fMRI responses during a Stroop task in older adults, pre- and post language-learning intervention. A group of 41 participants (age:60–80) from a predominantly monolingual environment underwent a four-month online language course, selecting a new language of their preference. This intervention mandated engagement for 90 minutes a day, five days a week. Daily tracking was employed to monitor progress and retention. All participants completed a color-word Stroop task inside the scanner before and after the language instruction period. Future research is needed to determine the optimal parameters for language learning as an effective cognitive intervention for aging populations. We propose that with sufficient engagement, language learning can enhance specific domains of cognition such as the executive functions. These results extend the understanding of cognitive reserve and its augmentation through targeted interventions, setting a foundation for future investigations. Volume 16 - 2024 | https://doi.org/10.3389/fnagi.2024.1398015 This article is part of the Research TopicLifestyle and Healthy Aging to Prevent Cognitive Decline and DementiaView all 28 articles Introduction: Numerous studies have highlighted cognitive benefits in lifelong bilinguals during aging manifesting as superior performance on cognitive tasks compared to monolingual counterparts the cognitive impacts of acquiring a new language in older adulthood remain unexplored we assessed both behavioral and fMRI responses during a Stroop task in older adults pre- and post language-learning intervention Methods: A group of 41 participants (age:60–80) from a predominantly monolingual environment underwent a four-month online language course selecting a new language of their preference This intervention mandated engagement for 90 minutes a day Daily tracking was employed to monitor progress and retention All participants completed a color-word Stroop task inside the scanner before and after the language instruction period Results: We found that performance on the Stroop task as evidenced by accuracy and reaction time improved following the language learning intervention we observed significant differences in activity between congruent and incongruent trials in key regions in the prefrontal and parietal cortex These results are consistent with previous reports using the Stroop paradigm We also found that the amount of time participants spent with the language learning program was related to differential activity in these brain areas we found that people who spent more time with the language learning program showed a greater increase in differential activity between congruent and incongruent trials after the intervention relative to before Discussion: Future research is needed to determine the optimal parameters for language learning as an effective cognitive intervention for aging populations We propose that with sufficient engagement language learning can enhance specific domains of cognition such as the executive functions These results extend the understanding of cognitive reserve and its augmentation through targeted interventions setting a foundation for future investigations This engagement is hypothesized to not only activate and strengthen these cognitive areas but also potentially induce neuroplastic changes within the brain the Stroop task provides an objective measure to assess a specific cognitive domain at baseline and after the intervention Any significant change in performance on the Stroop task from pre to post intervention can be attributed to cognitive changes potentially induced by the language learning process we used a pre-post intervention design with functional magnetic resonance imaging (fMRI) to explore the neural effects of language learning in older adults The study was initiated by conducting baseline fMRI scans for all participants to establish a neurological benchmark the participants underwent an online language learning program Participants were monitored daily for their performance and retention a second set of fMRI scans was conducted to identify any neural changes attributable to the intervention This pre-post design allows for the assessment of neural adaptations in response to new language acquisition in older adults The fMRI data were analyzed using standard neuroimaging techniques to observe changes in brain activity with a particular focus on regions associated with language processing and cognitive control This study was approved by the UNL Institutional Review Board (IRB) Office of Research & Economic Development The University of Nebraska at Kearney IRB acknowledged and honored the site agreement to cede IRB review to the University of Nebraska-Lincoln IRB regarding this study under the SMART IRB Master Common Reciprocal Institutional Review Board Authorization Agreement Per this agreement the UNL IRB serves as the reviewing IRB and the UNK IRB as the relying IRB Our participant cohort consisted of 41 healthy aged between 60 and 80 years (M = 66.63 min = 60; max = 77) all residing in a predominantly monolingual environment in Nebraska All participants had at least 14 years of education (M = 17.5 mirroring the demographics of the rural Nebraskan population All ethnic minorities were excluded based on proficiency in two or more languages Inclusion criteria consisted of being monolingual English-speaking adults aged 60–80 years of any gender with an electronic device and access to the internet with normal or corrected vision and hearing no diagnosed depression or neurological disorders we only included right-handed individuals to control for left-hemisphere dominance All participants were fully vaccinated for COVID-19 given that data were collected shortly after COVID-19 restrictions were lifted to avoid putting older adults at additional risk of exposure to COVID-19 Participants who were claustrophobic or did not have the ability to report to the Center for Brain or did not pass the MRI compatibility screener were excluded All participants had computer skills to enroll in the intervention program and access to the internet and a device All participants were screened using Montreal Cognitive Assessment (MoCA) and participants who did not score above the cut-off of 26 were excluded The Language Experience & Proficiency Questionnaire (LEAP-Q) (Marian et al., 2007; Kaushanskaya et al., 2020) was used to screen for second language knowledge LEAP-Q is a self-report toolbox to collect data on language knowledge use and exposure for all languages spoken by an individual and scores above 7 are taken as a measure of bilingual proficiency; a score of 0 indicates monolingualism Only participants with a score of 0 or 1 (minimal knowledge and at vocabulary level) were included Participants engaged in an online language learning program, Rosetta Stone1, in which they selected a language of their choice to learn. Rosetta Stone is a comprehensive computer-assisted language learning software developed by Rosetta Stone Ltd. This software employs an immersive method, inspired by the naturalistic way individuals learn their first language (Work, 2014; Zheng, 2024) The approach is characterized by the absence of translations or explicit grammar instructions and textual cues in the target language to convey meaning and foster language comprehension and production This methodology aligns with the communicative approach to language teaching which emphasizes the importance of interaction and using the language for real-life communication purposes This method mirrors the way a baby learns their mother tongue emphasizing immersion and natural acquisition the writing system is initially excluded from the learning process we did not exclude languages with different writing systems We used the educational version of Rosetta Stone which provided us with the possibility of monitoring the adherence to the program with detailed information about the number of minutes engaged in the program a detailed statistics about the activities in which the participant engaged the number of times each activity was repeated and scores on tests at the end of each lesson and each level The intervention spanned a duration of 4 months Participants were instructed to engage in language learning 5 days per week The online platform provided flexibility for participants to learn at their own pace and in a familiar environment potentially enhancing adherence to the program To ensure a consistent and effective learning experience we offered optional monthly zoom meetings to participants These meetings provided them with an opportunity to meet other participants Adherence to the intervention protocol was closely monitored we had access to log-in and time and type of language learning activities Participants could proceed with the lesson only if they passed the test with 80% accuracy or above This data was then used to assess the fidelity of the intervention and its potential impact on the cognitive abilities of the participants The color-word Stroop task (Stroop, 1935; Scarpina and Tagini, 2017) is a well-established neuropsychological test designed to evaluate cognitive control and executive function (Kane and Engle, 2003; Bari and Robbins, 2013) participants are presented with words denoting colors that are printed in congruent or incongruent colors (e.g. the word “red” printed in blue) They were required to identify the color of the “ink,” not the word itself which requires the inhibition of an automatic reading response the congruent trials included the names of colors that appeared in the same color that they read The incongruent trials included the names of colors that appeared in a different color that they read The participants were instructed to always pick the color of the word on the monitor (i.e. and ignore what the word “read.” The neutral condition consisted of the words “when,” “so” and “for” which were presented in different colors on the monitor Participants were instructed to respond with a right index finger key press for when the color of the word was yellow a right middle finger key press when the color of the word was red and a right ring finger key press when the color of the word was green The task was displayed to participants via a screen visible through a mirror mounted on the head coil The Stroop task paradigm was previously used in a number of studies (MacLeod, 1991; Kane and Engle, 2003) Our custom version of the Stroop task consisted of 108 trials divided into three conditions with each condition consisting of 36 trials Stimuli were presented with E-prime version 2.0 software (Psychology Software Tools Trials were presented in a pseudorandom order to control for sequence effects: (1) Neutral Condition: Departing from the traditional non-word letter strings our task incorporated common English words such as “When,” “So,” and “Like.” These words This adaptation aimed to control the impact of familiarity and semantic content on the participants’ response times and accuracy color words such as “Yellow,” “Red,” and “Green” were displayed in their respective colors The semantic and visual congruence would expedite response times leveraging the alignment between the word meaning and its visual presentation (3) Incongruent Trials: These trials featured color words in contrasting colors Each color word was repeated 12 times in each of the three incongruent colors resulting in a total of 36 trials for each condition Participants also practiced a short version of the same task outside of the MRI environment The only differences from the MRI Stroop task was that participants were seated at a desk and used a keyboard to respond MRI data were collected using a 3 T Siemens Skyra scanner with a 32-channel head coil at the Center for Brain Biology and Behavior at the University of Nebraska-Lincoln A T1-weighted high resolution anatomical scan (TR = 2.2 s FOV = 256 mm/100% phase slice thickness = 1 mm) was collected for precise alignment of functional data We also collected multiband echo-planar data (TR = 1 s FOV = 210 mm/100% phase slice thickness = 2.5 mm multiband acceleration factor = 3) during in-scanner task performance (one run of 490 s prior to language learning and one run of 490 s following the language learning intervention) The mean beta weight for each condition was extracted for each participant and time point for subsequent statistical analysis We calculated mean accuracy and reaction time data for congruent and incongruent trials for each participant. We ran an ANOVA with time (pre and post-language learning) and condition (congruent and incongruent) as repeated measures in JASP (ver. 0.16.2) (Love et al., 2019) The Holm-Bonferroni method was used for post hoc tests we monitored the amount of time that the participants used the online program The mean cumulative time dedicated to the intervention by our participants was 4,885 min (min = 1,218; max = 14,522) with a standard deviation of 2,470 min while the average time spent per day was 66.5 min accompanied by a standard deviation of 25.1 min Each language program is divided into three levels with participants required to take a proficiency test before advancing to the next level This indicates that all participants achieved a high proficiency level in the language lessons Performance on the Stroop task increases from pre to post language learning (A) The difference between accuracy on congruent and incongruent trials decreases following language learning (B) The difference between reaction time on congruent and incongruent trials decreases following language learning Asterisks indicate interaction p-value <0.05 Increased activation for incongruent relative to congruent trials in the Stroop task The main effect for condition (incongruent vs All significant results were characterized by greater activation for the incongruent relative to congruent condition We did not observe any significant clusters for the main effect of time (pre vs and we did not find any significant clusters for the condition (incongruent and congruent) by time (pre and post-language learning) interaction The results on participants’ performance in this study indicated that all participants achieved a high proficiency level (an average of % 96 on all proficiency tests) the time spent on the language learning program varied among participants (min = 1,218; max = 14,522; M = 4,885; SD = 2,470 min) Although within the design of this study it is not possible to tease apart exposure and use we used the cumulative time tracked by the language learning software as a variable that reflects exposure and use combined Changes in Stroop activation are related to the amount of time spent on the language learning program (A) Changes in Stroop task activation were extracted from four clusters identified in the main effect for condition These clusters were selected based on their involvement in the Stroop task in previous studies as well as from the main effect of condition in the current study Correlation between the change in Stroop activity and the time participants spent with the language learning program in the (B) Left lateral prefrontal cortex we reversed the subtraction operations so that more positive scores could be interpreted as increases in performance from pre to post intervention for both accuracy and reaction time the formula for accuracy was [(pre congruent – pre incongruent) – (post congruent – post incongruent)] there was greater between-participant variability in reaction times so to account for this variability we calculated the change score as a proportion of the difference between incongruent and congruent trials pre-intervention the formula for reaction time was [(pre incongruent – pre congruent) – (post incongruent – post congruent)/(pre incongruent – pre congruent)] we correlated the behavioral change scores with the amount of time spent on the language learning program As our hypothesis was that this relationship would be positive We did not observe a significant relationship between time spent on the language learning program and improvements in either accuracy or reaction time on the Stroop task While we did not observe a significant linear relationship between time spent on the language learning program and improvements in Stroop performance those who spent more time with the language learning program and those who spent less time Participants were placed in these groups if they spent more or less than the mean amount of time with the language learning program (4,885 min or ~ 81.5 h) Then we evaluated whether or not these groups were characterized by different levels of improvement on Stroop task performance (as described above) We found that the group who spent more time with the language learning program showed greater increases in Stroop accuracy from pre to post-intervention We did not observe any differences in reaction time performance between the groups who spent more or less time with the language learning program These data suggest that time spent with the language learning program was related to greater accuracy gains from pre to post-intervention on the Stroop While the effect on reaction time was not significant it was in the opposite direction as the accuracy effect which may be suggestive of a speed/accuracy trade off We hypothesized that learning a new language could serve as a beneficial intervention to boost cognitive performance for older adults By leveraging the cognitive complexity inherent in acquiring a new language we hypothesized that L2 learning would lead to specific cognitive domains such as executive functions We observed a significant condition (congruent vs incongruent) by time (pre and post-language learning) interactions on measures of accuracy and reaction time for the Stroop task These interactions were characterized by an increase in accuracy and a decrease in reaction time on incongruent trials post intervention Changes in performance on incongruent trials showed no significant change from pre to post-language learning This suggests the changes observed on incongruent trials are not general practice effects; but related to the intervention Behavioral results showed the Stroop effects and an improved performance post intervention as compared to pre intervention pre-post intervention comparisons reflected that the performance in Stroop task was more accurate post intervention as compared to pre intervention and the accuracy of the incongruent trials were improved and closer to the easier congruent trials which are less demanding in terms of conflict management Response times showed a similar effect to accuracy suggesting language learning influenced processing speed as well these data support the idea that Stroop performance improves following language learning While we did not observe any significant effect of time (pre vs or for the interaction (condition by time) we did observe a relationship between changes in the brain activity during Stroop task and the amount of time participants spent on language learning we found a positive relationship between changes in brain activity and time spent on the language learning program in the right lateral prefrontal cortex the left prefrontal cortex and the left parietal cortex as well as the right lateral prefrontal cortex This suggests that the time spent on learning a new language can modulate activation related to the Stroop task in regions included in the frontoparietal network (FPN) This superordinate network can describe how the executive function system with a common infrastructure can cater to the requirements of a network-specific and domain-specific demands of a particular task these brain areas have been reported as important brain areas that contribute to the cognitive advantage in lifelong bilinguals as compared to monolingual peers The current results suggest that learning a new language in older adults for 4 months may improve Stroop performance These results may also suggest that learning a new language in older adults can contribute to improving cognitive reserve and may contribute to postponing or slowing cognitive decline These results are in contrast to the current study where we did observe an effect of language learning on reaction time on the Stroop task It is unclear whether potential differences in the dose Altogether, in line with the previous reports (Bubbico et al., 2019; Meltzer et al., 2023) we provide evidence that even short-term language learning interventions can significantly reorganize and enhance neural network functions in older adults contributing to better cognitive performance in specific executive function tasks such as the Stroop task to note that while Stroop performance improved from pre to post-intervention and brain activity was modulated by the amount of time people spent with the language learning program the dose dependent effects of time spent on the language learning program and improvements in Stroop performance were tenuous Future studies should determine the optimal intensity duration and intensity of language learning programs as an effective cognitive intervention in older adults this intervention may potentially counteract the cognitive decline associated with aging through the enhancement of brain plasticity and functional connectivity The latter hypothesis remains to be tested We bring evidence that language learning at older ages may boost cognitive control performance as measured by improvements in the Stroop task This enhancement is associated with functional neuroplasticity in cognitive control areas of the brain indicating that acquiring a new language may actively influence function in these crucial regions these changes are observable improvements in tasks that require attentional control reflecting the transfer of cognitive gains from language learning to other cognitive domains These results align with the theory of cognitive reserve suggesting that intellectually stimulating activities like language learning can bolster the brain’s resilience to age-related decline we also acknowledge that the extent of these benefits depends on the dose of language engagement highlighting the importance of the amount and intensity of learning in realizing cognitive advantages These results present a promising avenue for non-pharmaceutical intervention for aging related cognitive decline low cost and potentially enjoyable approach to maintaining and enhancing cognitive health in the aging population As populations globally are experiencing increased longevity understanding how to maintain cognitive health in later life is of paramount importance Our study has a few limitations. First, our study’s design involved 41 participants, and is likely too small to allow for broad generalizations. In addition, Dichotomization of data may increase the risk of obtaining a false positive result (Altman and Royston, 2006) our study employed a pre-post intervention design without incorporating a control group or control condition limiting our ability to isolate the intervention effect from other potential influencing factors such as practice effects a lack of control groups limits drawing a strong conclusion for the causality of the intervention effects or controlling for confounding factors such as interaction with the researchers or the logistics of the language program such as logging in and out as well as limiting the generalizability of our findings The challenges associated with conducting randomized trials on second language acquisition as a cognitive intervention in older adults Future research approaches with bigger samples and designs that include control conditions are required this study potentially exhibits self-selection sample bias as the personality types of the participants and demographic homogeneity could have influenced the composition of our sample The participants were homogeneously white Caucasian which is reflective of the population characteristics of Nebraska Future multi-site studies should include all races and different ethnicities our sample consisted of older adults with moderate to high education levels (M = 17.5 Higher education level may have impacted the learning process or the cognitive demand required for learning a new language Future studies should explore the effect of education level on the cognitive effect of language learning the ethnic minorities were excluded due to their proficiency in two or more languages Future research should look at the cognitive effects of a third language in bilinguals of different ethnicities our priority was to allow participants to select the language of their choice This approach does not account for the effect of language distance Future studies should explore the language distance effect comprehensive research on cognitive effects of language learning is required to support our evidence for cognitive benefits of learning a new language in older adults Further research can provide invaluable insights into cognitive aging offering strategies not only for individual cognitive health but also for societal well-being The original contributions presented in the study are included in the article/supplementary materials further inquiries can be directed to the corresponding author The studies involving humans were approved by Rachel Wenzl - 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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: Ladan Ghazi Saidi, Z2hhemlzYWlkaWwyQHVuay5lZHU= Isah Ladan Bosso on Sunday heaved a sigh of relief and gave thanks to God that his side were able to keep their spot in the Nigerian Professional Football League (NPFL) with a 2-1 win over one of his former clubs Sports247 gathered that Sunday’s matchday 35 home win kept The Harmony Boys ninth on the NPFL log with 49 points while El-Kanemi are just one rung ahead of Heartland of Owerri who are the fist team in the top-flight league’s relegation zone Read Also: El-Kanemi Warriors’ Assistant Coach Mohammed Mohammed Tags Next Match Versus Remo Stars ‘Must Win’ While El-Kanemi will continue being anxious with their last three matches of the campaign Sunshine Stars of Akure and Lobi Stars of Makurdi in the war against relegation Bosso is happy that Bayelsa United are already assured of being in the NPFL come next season Flying Eagles’ former handler and current president of Nigerian Football Coaches Association (NFCA) admitted that Sunday’s victory was not easy to get against their very resilient visitors Bosso disclosed: “We expected that there was going to be a good fight from them That’s why the players that came from the bench were able to give us the result we still have to appreciate the resilience of the opponents Though they did not play in the second half what they they did in the first half the changes we made helped us get an impact.” The lanky tactician also took a closer look at the run of play in which either side scored through penalty kicks and acknowledged how his substitutions ultimately earned Bayelsa United the crucial winning goal pretty late in the encounter at Samson Yebowei Siasia Stadium in Bayelsa State’s capital “Two of the goals were interesting … penalty against us the goal that we scored to win the match could not be cancelled It was clinically executed through a lot of pressure from my boys and we finally got the winning goal.” He concluded by pointing out that the hosts’ goal came in the knick of time and too late for El-Ka to have any hope of staging a comeback for a draw leaving Bayelsa United picking up maximum points and gaining an assurance of being there next season in the NPFL there was no way they could balance the game again The only thing to do was maintain the line of defence we appreciate God with how we were able to seal up our position in the premier league for next season,” Bosso rejoiced and website in this browser for the next time I comment Congratulations are in order for electrical and computer engineering professor, Dr. Ladan Tahvildari Tahvildari was recently elected to the Board of Governors of the IEEE Computer Society (IEEE CS) for a three year term beginning 1 January 2025 The IEEE Computer Society is engaging computer engineers and industry professionals from all areas of computing IEEE CS sets the standard for the education and engagement that fuels continued global technological advancement Tahvildari leads the Software Technologies Applied Research (STAR) Group at the University of Waterloo Her research is in the areas of decision-making approaches for self-adaptive software systems including adaptive security analyzing architectures to manage cloud applications and scalable similarity search over big data Tahvildari is a member of the Association for Computing Machinery (ACM) ACM Special Interest Group on Software Engineering and the Institute of Electrical and Electronics (IEEE) She has been an elected Member-at-Large (2016-2018) for the IEEE Technical Council of Software Engineering (TCSE) Tahvildari is the current IEEE TCSE chair (since 2020) She is currently a Member-at-Large of the IEEE Technical Activities Committee (TAC) She served for more than 10 years as Chair of the IEEE Women in Engineering (WIE) Affinity Group Professor Tahvildari is a fellow of the Canadian Academy of Engineering Staff and Faculty DirectoryContact the Department of Electrical and Computer Engineering Waterloo Engineering Faculty OpeningsProvide Website FeedbackEngineering Website Help Head coach of Bayelsa United Ladan Bosso believes his team deserved more than a point in their NPFL Match Day 23 clash with with champions Rangers International on Sunday.Both teams fought out a 0-0 draw at the Samson Siasia Stadium Yenagoa with chances opening up for either sides at the tail end of the game but none could convert.Bosso believes that the result could have been different if his side did better than they did in the first half especially by converting the scoring chances they had even when the match was going on in the first half I believed my team would get better in the second half and they did just that The performance in the second half was better than the first so that is the output of coaching.“The issue now is the players taking their chances as early as possible If they have taken those chances in the first half and get one or two goals in the first half which I saw those chances were available it could have been a different story in the end,” added the former Nigeria Under 20 coach.Bayelsa United with the draw stretched their mini-unbeaten run to three matches and are currently placed 12th on the league log five points above the dreaded relegation zone.Up next for the Prosperity Boys is a trip to Kwara United in Ilorin on Match Day 24 Katsina United 1 Heartland 0 Shooting Stars 1 Bendel Insurance 0 Elkanemi Warriors 1 Nasarawa United 0 Remo Stars 2 Kano Pillars 1 Niger Tornadoes 1 Plateau United 1 Ikorodu City 2 Kwara United 1 Abia Warriors 3 Sunshine Stars 0Akwa United 2 Enyimba 1 Rivers United 1 Lobi Stars 0 Enter your email address to subscribe to this blog and receive notifications of new posts by email Previous | Next By Harminder Phull. This article was originally published on Waterloo News housed within the Faculty of Environment at the University of Waterloo is a leader in sustainability research education and innovation to benefit the environment The centre plays a pivotal role in developing guidance and mobilizing solutions that address climate-related extreme weather risk across Canada and enable a more resilient country all levels of government and businesses to reduce negative impacts from extreme weather events “Heat-related illness and death are preventable,” states Caroline Metz “By putting protective measures in place before a heat wave occurs tenants and homeowners can reduce undue suffering and health risks from heat – including negative social impacts The Intact Centre’s heat protection infographics offer a ‘how to' guide that can help residents and communities stay safe.” The Heat Waves Design Challenge brought together experts from climate science and design to serve on the judging panel and identified novel ways of communicating the impacts of extreme heat and actions to protect people and communities The initiative profiled meaningful communication strategies for those seeking more information and awareness offering practical solutionsand emphasizing adaptation action rather than solely profiling the threat from heat waves Sponsored by the Environmental Design Studio and Shade the U.K. the contest received entries from around the world “It is encouraging to see innovative work on extreme heat from around the world recognized in an international design competition Communication is key to changing behaviours,” says Joanna Eyquem “It is not enough to identify what to do; the key challenge is to engage people in taking action to protect themselves as part of their everyday lives.”   Receiving commendation in this prestigious international challenge is a significant accolade for the Intact Centre It reaffirms the centre’s role in advancing climate resilience and emphasizes that effective communication on complex issues like extreme heat is not only possible With a future characterized by irreversible climate warming the Intact Centre remains committed to helping Canadians understand heat risk and implement protective measures that can safeguard health and well-being now This article was originally published on the Electrical and Computer Engineering news site Congratulations are in order for electrical and computer engineering professor, Dr. Ladan Tahvildari Tahvildari was recently elected to the Board of Governors of the IEEE Computer Society (IEEE CS) for a three year term beginning 1 January 2025 The Open Access movement seeks to promote free and open online access to academic information libraries are key partners in the open access movement This year the Library will be hosting a series of workshops throughout the week, highlighting some of the key supports the Library provides related to open access. Learn more and register for events on the Library website the new emergency notification system (ENS) provided by Regroup will be tested on a campus-wide basis for the first time The test will include the following communications channels:  Downloaded Regroup Mobile to your device and follow the login and recommended settings steps Ensured your cell phone number is up to date either in the app if you are staff Downloaded and installed the Desktop Alert tool onto your computer If you have any questions about the upcoming test, or about how to make sure Regroup’s app and desktop alert are installed properly on your devices, email ens@uwaterloo.ca  30 years ago: The Shawshank Redemption The Student Health Pharmacy (located in the lower level of the Student Life Centre) is offering flu shots with no appointments needed daily from 9:30 a.m. to 3:30 p.m. Call 519-746-4500 or extension 33784 for more info. COVID shots will be available on appointment basis only. 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Don McCrae Naismith Classic. Buy your tickets today!  Stay up to date on service interruptions, campus construction, and other operational changes on the Plant Operations website Optometry Laser Clinic underground water main work fire sprinkler system in Optometry will be out of order during the work but the fire alarm system will be operational The Daily Bulletin is published by Internal and Leadership Communications, part of University Communications Contact us at bulletin@uwaterloo.caSubmission guidelines | Subscribe to the e-newsletter The President of the Nigeria Football Coaches Association (NFCA) has expressed strong support for the newly appointed Super Eagles Head Coach Bosso emphasized that Chelle’s success would be a triumph for the entire nation Read Also: Done Deal: American Women Soccer League Side Signs Rivers Angels Striker, Chiamaka Okwuchukwu Commending the leadership of the Nigeria Football Federation (NFF) President Bosso highlighted the strategic nature of Chelle’s appointment He noted that Gusau’s passion for the advancement of Nigeria’s national teams is evident in his dedication to establishing solid structures for long-term success “The appointment of Eric Chelle is a testament to Alhaji Gusau’s vision and commitment to improving Nigerian football,” Bosso stated The NFCA has pledged its full backing to the new head coach assuring him of the necessary support to achieve his goals expectations are high for a promising and successful tenure under Chelle’s leadership Metrics details There is an arms race between beta-lactam antibiotics development and co-evolving beta-lactamases which provide resistance by breaking down beta-lactam rings We have observed that certain beta-lactamases tend to aggregate which persists throughout their evolution under the selective pressure of antibiotics on their active sites we find that existing beta-lactamase active site inhibitors can act as molecular chaperones promoting the proper folding of these resistance factors synthetic peptides designed to exploit the structural weaknesses of beta-lactamases by causing them to misfold into intracellular inclusion bodies This approach restores sensitivity to a wide range of beta-lactam antibiotics in resistant clinical isolates including those with Extended Spectrum variants that pose significant challenges in medical practice Our findings suggest that targeted aggregation of resistance factors could offer a strategy for identifying molecules that aid in addressing the global antibiotic resistance crisis since this molecule is an inhibitor that binds in the active site but when administered at low doses it increases the overall activity of the enzyme by increasing the folding efficiency A Aggregation propensity prediction of TEM-1 using TANGO (left) and structural views of the TEM protein with the APR predicted by TANGO highlighted (right) Structure image (not including signal peptide and thus APR1) generated with Yasara of pdb ID 1bt5 B Distribution of the number of APRs per 100 residues in the various SCOP categories of protein folds: all-alpha helical (a) or separate helical and sheet segments (d) The dashed red line indicates the position of the TEM protein C Structured illumination Microscopy (SIM) super-resolution image of E coli BL21 overexpressing a GFP fusion of TEM-1 showing a single representative micrograph of one out of three independent repeats performed D Heat denaturation of TEM-1 monitored by intrinsic fluorescence plotted as the BaryCentric Mean (BCM) of the fluorescence emission spectrum in the presence (red) and absence (blue) of tazobactam The melting temperature (Tm) is derived from these data and the error bars represent the standard deviation E Temperature-dependent evolution of the Right-Angle Light Scattering (RALS) intensity measured simultaneously with the data in D to monitor protein aggregation The aggregation onset temperature Tagg is derived from these data but showing a dose-titration of the beta-lactamase inhibitor tazobactam G Scatterplot of RALS intensity at 60 °C versus the tazobactam concentration (from F) Source data are provided as a Source Data file These results lead us to conclude that in the recent evolution of the TEM enzyme it has retained its intrinsic aggregation propensity and the pharmacological chaperone effect of tazobactam thereon A Schematic representation of the structure of the peptides B Ribbon representation of the superposition of the crystal structures of TEM (green The catalytic site of the beta-lactamase activity is indicated and the location of APR3 is shown in red C TANGO aggregation score and alignment of APR3 in TEM and SHV D Fractional Inhibitory Concentration Index determination of the indicated peptides versus the penicillin control on E Each of the five dots per condition indicates an independent experiment consisting of 96 data points FICI values below 0.5 indicate synergy (shaded in green) Values between 0.5 and 1.0 indicate additivity (shaded in yellow) and values greater than 1 indicate indifference (shaded in red) between the combined substances G FICI values for the TEM3.2 peptide on a range of E A Measurements of the hydrodynamic radius by Dynamic Light Scattering of 50 μM TEM3.2 in buffer alone or in the presence of LPS or polyphosphate (PolyP) The data show a single representative replicate B Amyloid-like aggregation kinetics of 50 μM TEM3.2 measured by Thioflavin-T (Th-T) fluorescence in the same conditions as A Three replicates are shown for each condition C Transmission Electron Micrograph of 50 μM TEM 3.2 incubated for 24 h in the same buffer as A with polyP negatively stained with 2% (w/v) uranyl acetate D Amyloid-like aggregation kinetics of 50 μM TEM 3.2 in the PolyP condition in A E Aggregation kinetics using pFTAA fluorescence emission of recombinantly purified TEM-1 based on an APR sequence of beta-galactosidase but now using a previously published off-target Pept-In The plots are the results of a single experiment A Brightfield and structured illumination microscopy (SIM) images of E coli strain UZ_TEM104 treated with TEM3.2 at 12 μM for 120 min and stained with pFTAA coli strain UZ_TEM104 treated with 12 μM FITC-TEM 3.2 in PBS for 120 min and stained with the red-shifted oligothiophene HS169 to visualize aggregation coli K12 MG1655 overexpressing GFP from a pBAD vectorn and treated with vehicle or peptide TEM3.2 E Western blot and quantification for the TEM beta-lactamase in the inclusion body (IB) fraction of E treated with 12 μM of the indicated peptide in PBS or control for 120 min The quantification is the result of the densitometric quantification of four independent experiments and shows the mean and the standard deviation Statistical testing was done using one-way ANOVA with Dunnett’s pairwise comparison to control (ns non-significant F Western blot and quantification for the SHV beta-lactamase in the IB fraction of E treated with 12 μM of the indicated peptide in PBS for 120 min or control Fluorescence-activated cell-sorting (FACS) (A) of E coli strain UZ_TEM104 mixed 50–50% with the same strain after heat-inactivation The cells were stained with pFTAA to monitor aggregation and propidium iodide (PI) to monitor cell permeabilization associated with cell death The plot shows a single representative run of three independent repeats coli strain treated for 4 h with 400 μg/mL penicillin but treated with 50 μg/mL TEM 3.2 in PBS for 4 h but treated with 400 μg/mL penicillin and 50 μg/mL TEM3.2 in PBS for 4 h Note: the horizontal and vertical lines correspond to the gatings used to obtain the quantifications shown in the corners of each image A Lysis of human erythrocytes (hemolysis) was assessed in the presence of the indicated concentrations of TEM3.2 for 2 h at 37 °C and normalized to the value obtained with 1% of the detergent triton The plot is the result of 3 replicates and shows the mean and the standard deviation B Cell viability using the CellTiter Blue assay of HeLa cells treated for 24 h with the indicated concentrations TEM 3.2 at 37 °C The plot is the result of three replicates and shows the mean and the standard deviation C Fluorescence micrography of HeLa cells co-cultured with E coli TEM104 and treated with FITC-TEM3.2 (green channel) DAPI (4’,6-diamidino-2-phenylindole) is blue D Experimental workflow of the in vivo model used in this study E–G Bacterial load of indicated organs of female C57BL/6JAX mice with a urinary tract infection with E treated with 30 mg/kg penicillin (oral) as well 10 mg/kg tazobactam (oral) or 10 mg/kg TEM3.2 via the indicated treatment route The data shown is from a single experiment with 12 animals for each group The result for each animal is shown as a dot where the box extends from the 25th to 75th percentiles the line in the middle of the box is plotted at the median and the whiskers go from the minimum to maximum values The statistically significant differences were determined using ANOVA followed by Dunnett’s multiple comparison test One control sample for bladder was removed as an outlier (ns non-significant The exact P-value in the tazobactam versus control comparison for bladder was 0.0077 for all other comparisons the P-value is only known to be <0.0001) These data provide proof of concept that the TEM 3.2 is capable of restoring sensitivity to the beta-lactam antibiotic ampicillin in vivo of this strain of beta-lactamase carrying E which could lead to therapeutic applications A Ribbon representation of the crystal structure of the NDM-1 beta-lactamase enzyme (pdb id 3pg4). The active-site residues are indicated in green, the targeted APR is shown in red. B FICI plot as described in Fig. 2 for the strains indicated treated with penicillin and peptide NDM1-1 the peptides show a striking selectivity between the three analyzed beta-lactamases as synergy is only observed between each specific pair of peptides and the enzyme it is targeting The downside of this is that different peptides need to be developed for each beta-lactamase enzyme but the advantage is that identifying inhibitors for newly emerging enzymes is much faster than identifying novel small molecules Although the peptides presented in this work have not been optimized in any way to have drug-like properties they already show efficacy in vivo by restoring sensitivity to beta-lactam antibiotic treatment in a murine bladder infection model This suggests the development of these molecules into drugs may be possible and that they could become part of the molecular arsenal to combat the global antibiotic resistance crisis A DynaPro DLS plate reader instrument (Wyatt USA) equipped with an 830 nm laser source was used to determine the hydrodynamic radius (RH) of the peptide particles Two hundred microliters of each sample (at 100 or 10 μM unless stated otherwise) were placed into a flat-bottom 96-well microclear plate (Greiner The autocorrelation of scattered light intensity at a 32° angle was recorded for 5 s and averaged over 20 recordings to obtain a single data point The Wyatt Dynamics v7.1 software was used to calculate the hydrodynamic radius by assuming linear particles The amyloid-specific dye Thioflavin-T (Th-T CAS number 2390-54-7) was used to study the aggregation state of peptides Two hundred microliters of each peptide sample (at 100 μM unless stated otherwise) was placed into a flat-bottom 96-well microclear plate (Greiner and the dye was added to a final concentration of 25 μM Germany) was used to measure fluorescence by exciting the samples at 440-10 nm and fluorescence emission was observed at 480-10 nm (or a complete spectrum ranging from 470 to 600 nm) Aggregation kinetics were obtained by placing 200 μL of the peptide solution with a final concentration of 25 μM thioflavin-T (Th-T) into a flat-bottom 96-well microclear plate Fluorescence emission was monitored at 480-10 nm after excitation at 440-10 nm Every 5 min Th-T fluorescence was measured The Cell Titer Blue assay was performed to evaluate the cell viability according to the instructions of the manufacturer (Promega The peptide treatments were done in DMEM medium without serum cells were seeded to approximately 20,000 mammalian cells per well in a 96-well flat-bottom plate (BD Biosciences 353075) and incubated at 37 °C with 5% CO2 and 90% humidity 20 μL of the CellTiter Blue reagent was added to each well and the plate was incubated for 1 h at 37 °C The fluorescence was measured at 590 nm by exciting at 560 nm with a ClarioStar plate reader (BMG Labtech Hemolytic activity was evaluated by measuring the amount of released hemoglobin Fresh blood was pooled from healthy volunteers (collected from Rode Kruis Vlaanderen erythrocytes were collected by centrifugation 3000 × g for 10 min The cells were washed with phosphate-buffered saline (PBS) several times and diluted to a concentration of 8% in PBS 100 microliters of 8% red blood cells solution were mixed with 100 μL of serial dilutions of peptides in PBS buffer in 96-well plates (BD Biosciences The reaction mixtures were incubated for at least 1 h at 37 °C after which plates were centrifuged for 10 min at 3000 × g The release of hemoglobin was determined by measuring the absorbance of the supernatant at 495 nm Erythrocytes lysed in 1% Triton were used as control for 100% hemolysis The antibodies and antibiotic product codes used are as follows: monoclonal anti-TEM (Abcam polyclonal rabbit anti-SHV (custom-made by Eurogentec chicken polyclonal anti-beta Galactosidase (Abcam Goat Anti-Mouse IgG HRP secondary antibodies (ab97040); Rabbit Anti-Mouse IgG HRP (ab6728); Goat Anti-Chicken HRP (ab97135) The antibiotics used for this study: Penicillin G sodium (Benzylpenicillin sodium and kanamycin CAS number 56-75-7 (Duchefa Biochemie) Determination of MIC values was performed using the broth microdilution method according to the EUCAST guideline which was performed in 96-well polystyrene flat-bottom microtiter plates (BD Biosciences) a single colony was inoculated into 5 mL Difco™ Mueller–Hinton Broth (BD Biosciences Ref 275730) and grown to the end-exponential growth phase in a shaking incubator at 37 °C Cultures were subsequently diluted to a MacFarland (0.5 optical density) to reach 106 CFU/mL in fresh MHB medium 50 µl of different concentrations of peptides ranging from 128 to 2 µg/mL were serially diluted to the sterile 96-well plate in MHB 50 µL of the diluted bacteria in MHB were next pipetted into 96-well plates to reach the final volume of 100 µL The bacteria grown with the maximum concentration of carrier and medium were considered positive and negative controls The plates were statically incubated overnight at 37 °C to allow bacterial growth OD was measured at 590 nm using a multipurpose ultraviolet–visible plate reader and the absorbance of the bacterial growth was measured using an absorbance reader Bacterial growth was also visually inspected which agreed well with the OD reading The beta-lactamase assay procedure is based on the hydrolysis of the substrate Nitrocefin which produces a colored product (detectable at OD = 490 nm) that is directly proportional to the quantity of beta-lactamase activity This experiment was carried out in 96-well black polystyrene flat-bottom microtiter plates (BD Biosciences) 50 μl of different concentrations of peptides or tazobactam in PBS were added to each well followed by 50 μl of beta-lactamase protein at a final concentration of 12 ng The control heat was heated for 1 h at 95 degrees Celsius Each well received 5 μl of Nitrocefin at a stock concentration of 0.5 mg/mL Nitrocefin The hydrolyzed Nitrocefin was identified by absorption at 490 nm which is proportional to the amount of beta-lactamase activity a total volume of 100 μL of Mueller–Hinton broth was distributed into each well of the 96-well plates The first compound (peptide) of the combination was serially diluted vertically (128 0 μg/mL) while the other drug (Beta-lactam or Kanamycin) was diluted horizontally in a 96-well plate (from 3200 to 3 μg/ mL) The total volume of each microtiter well was inoculated with 100 μL of MHB containing 1 × 106 CFU/mL bacteria The plates were incubated at 37 °C for 24 h under aerobic conditions without shaking Calculation of the FICI is used to analyze the results of the checkerboard assay by estimating the degree of synergistic effect FICI is calculated as the sum of the individual fractional inhibitory concentrations (FICs) for each drug (where MIC A and MIC B denote the MIC of each drug alone and MIC AA+B and MIC BA+B denote the concentrations of A and B in the drug combination) FICI = (MIC AA+B/MIC A) + (MIC BA+B/MIC B) the combination of antibiotics is considered as a synergistic effect Bacterial cells in cleaned suspensions were stained with both propidium iodide (PI) and FITC-labeled peptides to evaluate the killing rate and peptide uptake in a two-dimensional analysis coli cells (106 CFU/mL) were washed with PBS and treated with peptides at sub-MIC (0.25 x MIC) and sub-MIC of Penicillin for several hours at 37 °C Treated bacteria were washed with PBS buffer two times One microliter of PI (Invitrogen) was added to the bacteria and incubated for 5 min The bacteria were counted by FACS to reach 40000 events To correlate the activity of the peptides with cell death the fluorescence intensity was measured in two channels using the GalliosTM Flow Cytometer (Beckman Coulter FITC: excitation 490 nm and emission 525 nm Heated bacteria at 90 °C for 10 min were used as PI-positive control The bacterial cultures were washed with PBS and the number of bacteria was adjusted to 108–109 cells/mL Bacteria were then treated with peptides (at sub-MIC or MIC concentration based on the aim of the study) or buffer for 2 h at 37 °C cells were treated with LCO dyes (pFTAA; AmytackerTM680 or AmytackerTM545: final concentration of 0.5 µM; Ebba Biotech and excitation spectra for each dye were measured based on the standard Ebbabiotec advice (ebbabiotech.com) Overnight cultures of bacteria were centrifuged for 30 min at 4000 × g and cells were washed with physiological water (NaCl 0.9%) Bacterial cells were treated by peptide at the appropriate concentration for at least 2 h at 37 C The bacterial pellets were washed with 10 mL buffer A (50 mM HEPES 1.0 mM EDTA) and centrifuged at 4 °C for 30 min at 4000 × g The supernatant was discarded and 20 mL of buffer B (buffer A plus 1 tablet of the protease and phosphatase Inhibitor Cocktail (ab201119 a High-Pressure Homogenizer (Glen Creston Ltd) with the pressure set to 20,000–25,000 psi was used on ice the suspensions were sonicated (Branson Digital sonifier 50/60 Hz) on ice with alternating 2 min cycle (15 pulses at 50% power with 30 s pauses on ice until completing 2 min total sonication time) The lysed cells were centrifuged at 4 °C for 30 min at 11,000 × g The precipitated fraction was afterward resuspended with 10 mL buffer D (buffer A plus 0.8% (V/V) Triton X-100 and the suspension was sonicated to ensure the pellet was completely dissolved Centrifugation was performed at 4 °C for 30 min at 11,000 × g the pellet was suspended in 500 μl of buffer F (50 mM HEPES Plasmids were obtained from Genscript (USA) vector construction services TEM (870 bp) and SHV (894 bp) were each sub-cloned into a PUC57 vector cloning site NdeI/ XhoI with an N-terminal HIS-tag followed by the TEV cleavage site coli BL21 (DE3) by inducing with 1 mM IPTG overnight at 20 °C Cells were harvested by centrifugation (15 min at 5000 rpm (2800 x g) at 4 °C) 200 mM Tris pH 8.5 plus protease inhibitors (mini ETDA free (Sigma-Aldrich) one tablet per 25 mL of buffer) and lysed using a high-pressure homogenizer (EmulsiFlex C5 The cell debris was removed by centrifugation (30 min and the soluble lysate was loaded on a size-exclusion chromatography (SEC) column 26/600 75 pg column (column vol 320 mL The protein was equilibrated with buffer 50 mM Tris pH 8.5 A multiple cloning site containing EcoRI and SpeI restriction sites was introduced C-terminally of the linker sequence through site-directed mutagenesis (using the New England Biolabs Q5® Site-Directed Mutagenesis Kit) SHV and TEM sequences with EcoRI and SpeI restriction sites at their N- and C-terminus were produced through PCR amplification from the expression constructs used for purification (discussed above) both the vector and PCR inserts were digested with SpeI-HF® and EcoRI-HF® (New England Biolabs) and ligated according to the manufacturer’s instructions For protein expression and solubility analysis bacterial strains were grown overnight in Lysogeny Broth (LB DifcoTM) supplemented with Ampicillin for GFP expression and both Ampicillin and chloramphenicol for co-expression of the GFP constructs with pKJE7 The overnight cultures were diluted 1:100 in fresh LB supplemented with the appropriate antibiotics and grown to an OD of about 0.6 after which expression was induced with 0.2 % arabinose Expression was allowed to proceed for 3 h after which cells were lysed in B-PER™ reagent (ThermoFisher USA) supplemented with 0.1 mg/mL lysozyme (Sigma-Aldrich) Complete™ Protease Inhibitor Cocktail (Sigma-Aldrich) and Pierce™ universal nuclease for cell lysis (ThermoFisher) after which soluble and insoluble fractions were separated through centrifugation at 17,100 x g for 30 min at 4 °C and the insoluble fraction dissolved in an equal volume of 8 M urea GFP in soluble and insoluble fractions was then quantified through SDS-PAGE followed by Western blotting Blots were developed using chemiluminescence after incubation with an anti-GFP antibody (Antibody 2555 S Cell Signaling Technologies) or anti-DnaK antibody (D8076 USBio USA) and an HRP-conjugated secondary antibody Blots were quantified using Bio-Rad’s Image LabTM Software Soluble GFP fractions were determined by calculating the ratio of soluble over total (soluble + insoluble) protein Female C57BL/6Jax mice of 6 to 8 weeks with uniform weight (between 20 and 23 g) were used in this study (Harlan four mice per cage on softwood granules as bedding The room was kept between 21 °C and 25 °C with 12/12 h light–dark cycles The animals had free access to water and pelleted rodent food To avoid stress-induced confounding factors the mice were transferred to the lab one week before experimental manipulation female C57BL/6Jax mice female mice were deprived of water for at least 1 h they were anesthetized by IP administration of the mixture of ketamine (Nimatek)/xylazine (XYL-M 2% BE-V170581) The bladder of the mouse was massaged with fingers and pushed down gently to expel the remaining urine Mice were slowly inoculated urethrally with 50 µL of a bacterial suspension slowly over 5 s to avoid vesicoureteral reflux (108 CFU/ mouse) using a sterile catheter (pediatric intravenous-access cannula (GS391350)) The catheter was removed directly after inoculation the animals were visually monitored for full recovery all mice received Ampicillin (30 mg/kg_PO-orally) and at the same time 3 groups of animals received the peptides via different administration routes (10 mg/kg_IV—intravenous; IP—intraperitoneal or SC—sub-cutaneous) and the positive control groups received tazobactam (10 mg/kg The negative control groups received vehicle or saline (IV administration) all mice received a second injection with the same concentration of each treatment as explained above ureter) were washed with PBS and were homogenized (Thermo Savant FastPrep FP120 Homogenizer/24 s) The homogenized tissues were serially diluted and cultured on blood agar plates The plates were incubated overnight at 37 °C and the number of bacteria was measured by CFU value Human HeLa cells were grown to create a confluent monolayer on a small-cell-view cellular plate with a glass bottom (Greiner Bio-One GmbH/35 mm Ref: 627860) for imaging purposes cells were inoculated for 24 h with 200 μL of a mixture of overnight culture of TEM1 E Cells were stained for 30 min with CellMask Deep Red plasma membrane dye (ThermoFisher catalog # C10046) and 1 L of NucBlue reagent (Invitrogen) and 2 mL paraformaldehyde 4% was added to the dish for fixation The dish was kept at room temperature for 6 h the co-cultured cells were rinsed at least three times with 1 mL PBS Bacteria were fixed by adding 2.5% paraformaldehyde and 0.04 % glutaraldehyde (final concentrations) to the culture media followed by incubation at room temperature for 15 min and 30 min on ice Bacteria were then washed in PBS and resuspended in GTE buffer (50 mM glucose cells were transferred to a glass slide and covered with a coverslip Imaging was performed using a Zeiss Elyra S.1 system in the VIB BioImaging Core at KU Leuven Statistical analysis was performed with Prism or R and ANOVA to determine the statistical significance of differences between samples unless otherwise indicated Significance levels: * for P < 0.05; ** for P < 0.01; *** for P < 0.001; **** for P < 0.0001 Non-significant differences are not separately labeled All mouse experiments were conducted according to the national (Belgian Law 14/08/1986 and 22/12/2003 Belgian Royal Decree 06/04/2010) and European (EU Directives 2010/63/EU All protocols were approved by the KU Leuven Institutional ethics committee on animal experimentation All relevant animal characteristics and housing conditions are specified in the materials and methods All blood samples were obtained from healthy volunteers from the biobank of the Red Cross Flanders in accordance with all relevant national legislation Blood samples were completely anonymized prior to transfer to our facilities Ethical approval was obtained from the medical ethical committee of the University Hospitals Leuven (study number S60497) Only the PCR systems with ANSI/ATCC standard ASN-0002 were aligned in the final comparison Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article The code of all analysis scripts and in silico datasets used are available from the corresponding authors upon reasonable request An enzyme from bacteria able to destroy penicillin Extended-spectrum beta-lactamases in the 21st century: characteriszation and detection of this important resistance threat Van Puyvelde, S., Deborggraeve, S. & Jacobs, J. 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Multiple Global Suppressors of Protein Stability Defects Facilitate the Evolution of Extended-Spectrum TEM β-Lactamases. 404, 832–846 https://doi.org/10.1016/j.jmb.2010.10.008 (2010) Abriata, L. A., M. Salverda, M. L. & Tomatis, P. E. Sequence-function-stability relationships in proteins from datasets of functionally annotated variants: The case of TEM β-lactamases. 586, 3330–3335 https://doi.org/10.1016/j.febslet.2012.07.010 (2012) The role of residue 238 of TEM-1 beta-lactamase in the hydrolysis of extended-spectrum antibiotics Crystal structure of the OXA-48 beta-lactamase reveals mechanistic diversity among class D carbapenemases Purification and biochemical characterization characteriszation of the VIM-1 metallo-beta-lactamase Kumar, G., Issa, B., Kar, D., Biswal, S. & Ghosh, A. S. E152A substitution drastically affects NDM-5 activity. FEMS Microbiol. 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H., Thathireddy, A. & Hsieh, M. H. Transurethral induction of mouse urinary tract infection. J. Vis. Exp https://doi.org/10.3791/2070 (2010) Download references The Switch Laboratory was supported by grants from the European Research Council under the European Union’s Horizon 2020 Framework Program ERC Grant agreement 647458 (MANGO) to J.S. the Flanders Institute for Biotechnology (VIB) the Funds for Scientific Research Flanders (FWO and postdoctoral fellowships 1231021N to Ladan K and 12S3722N to B.H.) and the Flemish Agency for Work and Innovation (VLAIO We thank the following core facilities for training and access to their instrument parks: the VIB BioImaging Core at KU Leuven (SIM microscopy) the KU Leuven Flow and Mass Cytometry Facility and the Electron Microscopy core of VIB-KU Leuven Leuven) for kindly providing clinical isolates These authors contributed equally: Ladan Khodaparast Department of Cellular and Molecular Medicine Laboratory of Clinical Bacteriology and Mycology Department of Microbiology & Immunology contributed to the interpretation of the results All authors provided critical feedback and helped shape the research are named as inventors in a patent (WO 2022/184821 ‘Beta-lactamase inhibitors’) filed by their host institute VIB describing the peptides mentioned in this manuscript (Status: international PCT phase The remaining authors declare no competing interests reviewers for their contribution to the peer review of this work Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41467-023-41191-z Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Sign up for the Nature Briefing newsletter — what matters in science Title: Towards Guaranteed Artificial Intelligence Methods the integration of artificial intelligence (AI) into mechatronics systems has demonstrated significant promise across diverse industries ensuring the reliability and trustworthiness of AI procedures particularly in sensitive manufacturing applications I will address the issue of guaranteeing AI procedures through hybrid control methods which facilitate the development of certified learning algorithms essential for ensuring dependable performance in complex mechatronic systems I will explore how adversarial machine learning techniques can enhance safety and security in control procedures for manufacturing and aerospace applications we aim to advance the application of AI in critical industrial domains while ensuring robustness and reliability in operational outcomes The seminar explores the practical implications of these methodologies demonstrating their potential to advance manufacturing automation and fortify control systems in aerospace engineering By examining the intersection of certified learning and adversarial machine learning with mechatronics this presentation illuminates innovative pathways toward enhancing efficiency and resilience across vital industrial sectors Contact Us Provide website feedback The Bayelsa State government has issued a stern warning to Bayelsa United threatening to ban the club if they are relegated at the end of the season the government has given Bayelsa United’s technical adviser and his coaching staff a two-game ultimatum to secure their jobs At a recent meeting with the coaching team and club management in Yenagoa Commissioner for Sports Development Daniel Igali stated that the ultimatum was necessary due to the team’s ongoing struggle to secure wins Igali emphasized that the government cannot continue to “fold its hands” while the team’s performance declines especially given the significant financial support provided by the state The two-game ultimatum will begin with Bayelsa United’s upcoming fixtures against Rivers United in Port Harcourt and Katsina United Igali made it clear that if Bosso’s team fails to secure victories in both matches the entire technical crew could lose their positions Bayelsa United sits in 18th place with just 10 points from 10 games who took charge of the team at the start of the season with his future hinging on the outcomes of these next two games Bayelsa United will travel to face Rivers United in a South-South derby at the Adokiye Amiesimaka Stadium in Port Harcourt followed by a home match against Katsina United at the Samson Siasia Stadium in Yenagoa