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Gigira steal 3-2 win over FC POM in extra time

first_imgGigira took a 1-0 lead before half time when July Elijah scored in the 34th minute to put Gigira in front.FC Port Moresby responded in the second half through a double from Jamal Seeto to see them steal a 2-1 lead in the 69th minute.But Gigira leveled up a minute later through Ian Yanum.The game looked certain to go into a draw with the clock winding down.But it took brilliance to steal the win during extra time and Gigira ‘ s Moses Arisim when given the ball didn’t let his his team down powering a ball through from outisde the penalty box to beat the goal keeper.last_img read more

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Williams eats dog food but reaches Italian Open quarters

first_imgThe world number one tried “a spoonful” of food meant for her dog Chip before beating fellow American Christina McHale in straight sets in Rome.”I thought ‘what the heck, I’m gonna try a piece, it looks good’,” said the 34-year-old.”Fast forward two hours – I just ran to the toilet like I thought I was going to pass out.”In a video posted on Snapchat before her match with McHale, Williams explained she sampled a dish of chicken and rice offered on a ‘doggy menu’ at her hotel.”It did taste weird,” she said. “I force-swallowed it. It tasted kind of like house cleaner. I don’t know what they put in these dog foods, but Chip liked it.”I don’t think it’s consumable for humans – they should have wrote that! So now I feel really sick. It was just a spoonful but I don’t feel so good.”Williams recovered in time to defeat McHale 7-6 (9-7) 6-1 and set up a meeting with Svetlana Kuznetsova – who beat fellow Russian Daria Gavrilova – in the last eight.last_img read more

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APNG and PNGSF sign MOU

first_imgUnder the MOU, the parties will work together to develop the content knowledge and best practiced skills of the sport of athletics to the next level, targeting Physical Education teachers, coaches, trainers and athletes.PNG Sports Foundation Director of Major Events and Marketing, John Susuve was on hand to sign the MOU on behalf of the Executive Director, along with APNG President Tony Green.Talks are underway for APNG to provide the course materials for the Human Movement Studies branch of the NSI to make a submission to the University of Goroka for teaching.It is anticipated that if all goes well, a number of promising athletes will be identified through APNG’s own High Performance Division and NSI activities, to enrol at what will become a National Sports Academy, with enrolment complying with the set procedures of Stem 101 and the TVET Institute of UOG. In signing the MOU, Susuve said that the Foundation was very happy to work closely with National Federations and especially a sport like athletics which, being a key sport for PNG on the international stage, will lift the profile of the country.  Green added that NSI is the logical place for athletes to train because of its central location, great climate and the training and accommodation facilities.He said he hoped that the government will see the benefit in upgrading the facilities instead of focusing all its efforts on infrastructure in Port Moresby.Apart from the pursuit of tertiary education programmes, APNG and NSI plan to re-introduce the scholarship program, whereby a small number of quality developing athletes will relocate to NSI and attend high school.last_img read more

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Rape is not equivalent to “deflowering”

first_imgAs Guyana joins the rest of the world in observing Child Protection Week under the theme “Children’s Safety and Security, Our Priority”, the haunting incidents of rape and sexual assault against women and girls continue to trouble this nation. The sad reality of this recently unfolded when a 21-year-old mother of one died following a sexual attack by a minibus driver. So severe were her injuries that a child is now left motherless. In 2015, there were over 230 reports of rape, but only 36 persons were charged. Compounding this actuality is also the fact that there is a stark court backlog on tackling cases of sexual violence.A recent United States Department report on human rights outlined that in Guyana, a high number of rape and sexual assaults are unreported to authorities, citing that this was most likely as a result of fear of stigma, a lack of confidence in authorities, retribution, or further violence.As with any form of violence, sexual violence tears at the fabric of a country’s well-being. However, when the agency responsible for helping victims of rape describes this horrendous crime as mere “deflowering”, the sad unravelled truth of our country’s approach to this crime is evident. “Deflowering” means to deprive (a woman) of her virginity, but is that what rape is? Mere deflowering? The Social Protection Ministry, in its statement on Guyana’s observances for Child Protection Week, stated that “incest and underage sexual activity in childhood (are) also of grave concern to the Childcare & Protection Agency (CPA), an arm of the Ministry. This deflowering of our children must stop.”It is frighteningly obvious that the Social Protection Ministry needs a trained psychologist to educate its staff about the true meaning of rape, particularly child rape, which is not simply “deflowering” even if the victim was virginal. Rape is more than “deflowering”; rape is sexual abuse, a lifelong scar. The Ministry needs to also be enlightened that rape and other forms of sexual assault have traumatic psychological, emotional, physical, social, interpersonal, and financial impact on victims. According to a study conducted by Rape Victims Advocates (RVA), each survivor reacts to sexual assault in their own unique way. Personal style, culture, and context of the survivor’s life may affect these reactions. Some victims may tell others right away what happened, others will wait weeks, months, or even years before discussing the assault, if they ever choose to do so.Earlier this year, Social Protection Minister Volda Lawrence came in for much criticism after she made some unfortunate remarks and had a casual approach in defence of a man, who was charged for sexual molestation. The Minister, in defence of the man, was quoted by another section of the media as saying, “This is a family issue that has been going on and on and on and on for whatever reason, I can’t tell you, because if I had a brother, even if there was an accusation, this is not how I would go about helping him.”What was rather disappointing is that the alleged molester’s sister further alleged that she told the Minister that her brother needed to be jailed for his involvement, but Lawrence asked her not to pursue such actions.Less than six months later, there is a statement issued by the Ministry the same Minister heads defining rape of children as simply “deflowering”.The Social Protection Ministry is where victims of such a dreadful crime seek refuge not only for their physical well-being but also for justice. As such, if rape/sexual assault victims’ tragedy is seen as mere “deflowering” by this ministry, then where can they truly seek help? This time around, President David Granger needs to do much more than modestly ask the Minister for an explanation.last_img read more

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GECOM being run like old-time cake shop (Pt 1)

first_imgDear Editor,With each passing day, the inherent fault lines eroding the democratic purpose of the Guyana Elections Commission (GECOM) threaten to graduate into a devastating tsunami. In fact, the magnitude of evidence in the widely circulated public media from many disappointed stakeholders puts the rebranded image of the organisation as tantamount to that of an old-time cake shop being run with hundreds of millions of taxpayers’ money.It is clear that the undercurrents have further deepened, since the strongly-challengeable, unilateral appointment by President Granger of the Chairman, Justice (retired) James Patterson. Nothing significant has so far been done by the Chairman to remedy the problematic issues at GECOM. Rather, things seem to have gotten worse, rendering the decaying grey matter incapable of adjusting to, or overseeing, a meaningful input that would cleanse the infested cake shop operations.In essence, when appointed, Commissioners have to take to the public media to air the overwhelming internal inefficacies and dirty linen permeating GECOM. It is a clear sign that we are fast approaching breaking point!Numerous published evidence -based revelations provide a very dismal picture of the many distasteful happenings being conducted within the organisation. Under Chairman James Patterson’s watch, Chief Executive Officer Keith Lowenfield acts as a lord unto himself, and has become even more emboldened to unleash another imbued ‘Town Clerk-like’ display.It was recently reported that when asked about approaches to expending on public relations projects, Lowenfield informed GECOM’s statutory meeting that once the Finance Ministry gave the accounting officer the approval to expend funds for any purpose, the GECOM Secretariat was not required to bring the issue before the Sub-Committee or the Commission.The seriousness of this erroneous response cannot be understated. Lowenfield pretends to be not any wiser following highly prosecutable findings contained in the report of the 2017 Auditor General’s examination of GECOM’s financial activities. It is clear that the procurement mechanism is being continually abused under a created guise of so-called urgent requirements for the same activities year after year; election after election. In essence, the internally applied approaches are being deliberately manipulated to accommodate fraud and handpicked beneficiaries.In a public entity such as GECOM, properly accountable practices are enshrined in the approved procurement legislation to address procedures that must be followed in the pre-procurement cycle; the cycle, and the post- procurement cycle. Critically, procedures in the law are specific to how this firm procures in terms of mandatory compliance procedures that support accountability. Particularly, they address the tender process, including forms of tendering — whether selective, public, or special; and consider strongly the Terms of Reference for the critical activities.In the GECOM setting, these do not often change, and are repeatable, since they are often informed by the plan for the specific elections and the related budget. This column, on numerous occasions, called for release of the GECOM budget, which often seems absent, abstract or lacking, in the interest of transparency and accountability.It is therefore appalling that the Commission would entertain such responses from the CEO of the Secretariat when requests for clarification are made by Commissioners.Notably, the Chairman of the Commission and the CEO of the Secretariat had, months ago, indicated the readiness of the organisation to fulfill the rudiments of the November 12th Local Government Elections.One had expected that such confirmation would have been driven by structured planning and budgeting, approved by the Commission (including all commissioners). One had expected that the execution of the Secretariat’s plan would have been strongly monitored, supported by a structured schedule that is devoid of occurrences of fraudulent financial manipulation to benefit a few. One would have expected that the high-risk elements which undermine the required level of professionalism would have been identified, and approaches to mitigate them would have been employed.Sincerely,Neil Kumarlast_img read more

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Clogged drains, poor drainage lead to flooding in Region 2

first_imgSeveral businesses in the commercial centre at Anna Regina, Region Two (Pomeroon-Supenaam) were forced to close their doors as a result of flooding.When Guyana Times visited Anna Regina early Tuesday morning, several businessmen were seen bailing water from their business places. Clothes and electronic equipment vendors at Anna Regina were also forced to close and secure their items as a result of excessive water.A house under water at the Anna Regina Housing SchemeAccording to one of the electronic vendors, when he opened his shop he noticed a considerable amount of water accumulated from heavy rainfall. He said he immediately started to sop water and move his transformer to higher grounds. Businessmen next to him were also seen doing the same.Meanwhile, a drive around the town of Anna Regina revealed that several houses in the scheme were inundated with water. At Lima, residents remained under water and were counting their losses daily. According to several residents, the pump and sluice, although in operation, are not draining the lands fast enough. Many poultry pens and kitchen gardens are currently flooded.A Queenstown family was forced to stay indoors as a result of floodwatersAt Queenstown village, some houses are under water. Residents were seen in the floodwaters and according to them, several of their drainage trenches are clogged with overgrown bushes. Like the Lima residents, Queenstown residents are counting thousands of dollars in losses.In the extreme south of the Essequibo Coast in areas such as Golden Fleece, Suddie, Good Hope and Vilvoorden, there was a high accumulation of water in the drainage trenches. Rice farmers are very worried and many of them are calling for the access dams in their respective areas to be rehabilitated.Region Two has been experiencing high intensity rainfall, but poor drainage compounded with clogged drainage trenches has led to flooding.last_img read more

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Mad rush for tickets to Crocodile Hunter’s memorial

first_imgSome 3,000 grieving fans, hundreds of whom camped on the street in Brisbane, Australia, overnight, were rewarded today with tickets to next week’s public memorial service for “Crocodile Hunter” Steve Irwin. The free tickets were distributed at three locations across Irwin’s home state of Queensland, and were snapped up within about 15 minutes. Melissa Power, a 34-year-old beautician, was at the front of the line in the state capital, Brisbane, and had tears in her eyes when she finally got her ticket. “It’s unbelievable,” she said. “I haven’t slept and am so overemotional I’m looking so forward to it.” AD Quality Auto 360p 720p 1080p Top articles1/5READ MOREThe joys and headaches of holiday travel: John Phillips Thousands lined up for tickets outside Irwin’s Australia Zoo. Some burst into tears after the tickets ran out. The public service for Irwin will be held Wednesday at the “Crocoseum” amphitheater on the grounds of the Australia Zoo, and will be a “celebration of his life, not a sad funeral,” his father, Bob, told reporters last week. Irwin was killed Sept. 4 when he was pierced in the chest by a stingray’s barb while filming a new TV show off Australia’s Great Barrier Reef. His death prompted an outpouring of grief around the world and in Queensland, where tens of thousands of fans turned out to lay flowers, candles and messages of support outside Australia Zoo. Although larger venues for the public event had been suggested, Irwin’s American-born wife, Terri, said her husband would have wanted the service held at the Crocoseum. Terri Irwin and the couple’s 8-year-old daughter, Bindi, are to speak at the service, along with Bob Irwin and his close friend and manager, John Stainton, the family said.165Let’s talk business.Catch up on the business news closest to you with our daily newsletter. Something went wrong. Please try again.subscribeCongratulations! You’re all set!last_img read more

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Olivia Hussey honored in T.O. for Mother Teresa role

first_imgTHOUSAND OAKS – People laughed, sighed and gasped, and then actress Olivia Hussey got a standing ovation from the crowd of about 200 people when she attended a showing this week of her film “Mother Teresa of Calcutta” and received an award for her portrayal of the famous nun. The special showing of the film was arranged by the Conejo Compassion Coalition, an interfaith group formed after the 2004 South Asian tsunami to help needy people abroad and at home. Hussey, known in part for her roles as Juliet in Franco Zeffirelli’s “Romeo and Juliet” and the Virgin Mary in the television miniseries “Jesus of Nazareth,” said she had dreamed for 25 years of portraying Mother Teresa on film and felt it was a miracle when she was offered the role. “People would say, `What else could you possibly want to play after Juliet and the Virgin Mary?’ and I said, `Mother Teresa,”‘ Hussey recalled. “That was 25 years ago. It was like a dream come true, because among all people, Mother Teresa was the one who inspired me the most.” AD Quality Auto 360p 720p 1080p Top articles1/5READ MOREThe joys and headaches of holiday travel: John PhillipsMother Teresa’s niece, Agi Bojaxhiu, came from Italy to help present Hussey with the 2006 Mother Teresa Award from the St. Bernadette Institute of Sacred Art based in Albuquerque, N.M. “I’m very moved,” Bojaxhiu said after she had seen the film and witnessed the standing ovation. “Olivia has really expressed the spirit of Mother. I couldn’t believe it. I must say, Mother Teresa is here with us in her spirit.” Tuesday’s gathering for the film at the Rockwell Science Center in Thousand Oaks and a reception at St. Patrick’s Episcopal Church on Wednesday were set up to bring people together in appreciation of the film, Hussey’s work and the work of the St. Bernadette Institute and the Conejo Compassion Coalition. Although 200 people saw the film, another 600 were unable to attend because of the auditorium’s size. “When I saw the film for the first time I knew people had to see it for inspiration, so that they too would be moved to become part of the coalition,” said Marilyn Kennedy, an actress, former Episcopalian nun and a leader of the group who was instrumental in setting up the Thousand Oaks event. “Right from the beginning the whole emphasis of the coalition has been on compassion and sensitivity to the needs of others.” “Mother Teresa of Calcutta” was released on DVD this summer by 20th Century Fox. At Tuesday night’s showing, Hussey was welcomed by Thousand Oaks Mayor Dennis Gillette and received a proclamation from a representative of Gov. Arnold Schwarzenegger. Other recipients of the Mother Teresa Award include Pope John Paul II, the Dalai Lama, Nelson Mandela, Jimmy Carter and Maya Angelou. Mother Teresa was a Roman Catholic nun who founded the Missionaries of Charity in India, where she worked with the poor of Calcutta. She said her mission was to “care for the hungry, the naked, the homeless, the crippled, the blind, the lepers, all of those people who feel unwanted, unloved, uncared for throughout society, people that have become a burden to the society and are shunned by everyone.” She received the Nobel Peace Prize in 1979 and died in 1997. She was beatified by Pope John Paul II in 2003. eric.leach@dailynews.com (805) 583-7602160Want local news?Sign up for the Localist and stay informed Something went wrong. Please try again.subscribeCongratulations! You’re all set!last_img
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Body of elderly Palmdale man found

first_img(818) 713-3730 160Want local news?Sign up for the Localist and stay informed Something went wrong. Please try again.subscribeCongratulations! You’re all set! AD Quality Auto 360p 720p 1080p Top articles1/5READ MOREWhicker: John Jackson greets a Christmas that he wasn’t sure he’d seeAuthorities were able to contact the elderly man on his cell phone, but were unable to pinpoint his exact location. “We couldn’t determine where he was – he seemed confused,” he said. “They lost contact with him at about 9 o’clock – it went straight to his answering machine.” Two sheriff’s helicopters and one fire chopper assisted in the search as overnight temperatures dipped into the 20s. Though Adlen was dazed and disoriented and unable to direct authorities to his location, Wright said, he had no known history of dementia. dana.bartholomew@dailynews.com PALMDALE – The body of an elderly Palmdale man who had became lost overnight after contacting authorities was found early today, a quarter-mile from his car. A volunteer canine-rescue team found the body of Gordon Adlen, 74, was found about 6 a.m., lying in a stream, Los Angeles Sheriff’s Lt. Ken Wright said. “It appears that he drove down a dirt road heading to one of the ranches and got stuck trying to get his car out and walked a quarter mile away,” he said. “It appears he had fallen into a stream, gotten soaked and succumbed to hypothermia.” Adlen had become the subject of an all-night search after being reported missing by his son at 7 p.m. Wednesday, Wright said. last_img read more

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Profile on starlet linked to £250k Leeds move with ‘unbelievable work rate’

first_img Arsenal transfer news LIVE: Ndidi bid, targets named, Ozil is ‘skiving little git’ England Under-21s vs France Under-21s (Tuesday, 8pm) – talkSPORTJapan vs England (Wednesday, 8pm) – talkSPORTScotland vs Argentina (Wednesday, 8pm) – talkSPORT 2England Under-21s vs Romania Under-21s (Friday, 5:30pm) – talkSPORT 2 Video Player is loading.Play VideoPlayMuteCurrent Time 0:00/Duration 2:00Loaded: 8.23%Stream Type LIVESeek to live, currently playing liveLIVERemaining Time -2:00 Playback Rate1xChaptersChaptersDescriptionsdescriptions off, selectedCaptionscaptions settings, opens captions settings dialogcaptions off, selectedAudio Tracken (Main), selectedFullscreenThis is a modal window.Beginning of dialog window. Escape will cancel and close the window.TextColorWhiteBlackRedGreenBlueYellowMagentaCyanTransparencyOpaqueSemi-TransparentBackgroundColorBlackWhiteRedGreenBlueYellowMagentaCyanTransparencyOpaqueSemi-TransparentTransparentWindowColorBlackWhiteRedGreenBlueYellowMagentaCyanTransparencyTransparentSemi-TransparentOpaqueFont Size50%75%100%125%150%175%200%300%400%Text Edge StyleNoneRaisedDepressedUniformDropshadowFont FamilyProportional Sans-SerifMonospace Sans-SerifProportional SerifMonospace SerifCasualScriptSmall CapsReset restore all settings to the default valuesDoneClose Modal DialogEnd of dialog window.Close Modal DialogThis is a modal window. This modal can be closed by pressing the Escape key or activating the close button.PlayMuteCurrent Time 0:00/Duration 0:00Loaded: 0%Stream Type LIVESeek to live, currently playing liveLIVERemaining Time -0:00 Playback Rate1xFullscreen IN DEMAND REVEALED Getty Liverpool’s signings under Michael Edwards – will Minamino be the next big hit? TOP WORK LIVING THE DREAM The biggest market value losers in 2019, including Bale and ex-Liverpool star Unless you support the Cumbrians or follow every second of League Two, you probably haven’t heard of McCarron.So we’ve taken a look at the winger ahead of a potential move to the Championship.Who is Liam McCarron?The Preston-born forward joined Carlisle’s academy at Under-14s level, before signing his first professional contract last September.During his debut season, he featured 20 times, mainly as a substitute, as the Cumbrians finished 11th in League Two. talkSPORT is your home of live football! Here’s what’s coming up on talkSPORT and talkSPORT 2… Tony Cascarino backs Everton to sign two strikers for Carlo Ancelotti 1 Man United joined by three other clubs in race for Erling Haaland center_img targets Where every Premier League club needs to strengthen in January LATEST TRANSFER NEWS Carlisle winger Liam McCarron has emerged as the surprise favourite to become Leeds’ first signing of the summer.The White are reportedly plotting a £250,000 bid for the 18-year-old, who joins Helder Costa, Ryan Kent, Harry Wilson and Ben White on Marcelo Bielsa’s rumoured shopping list. Cavani ‘agrees’ to join new club and will complete free transfer next summer The Whites are believed to be rivalling Wolves, Sheffield United and Derby for the 18-year-old’s signature. LIVE ON talkSPORT taklSPORT ranks every Chelsea manager in the Roman Abramovich era McCarron registered one assist, but he is still searching for his first professional goal.Carlisle academy manager Darren Edmondson said: “Liam has got no ego, no airs and graces, he’s just a good lad who wants to do well.”How does he play?Leeds famously missed out on the signing of Manhcester United’s new star Dan James in January – and McCarron is cut from the same cloth.The youngster, who can play on either flank, has blistering pace. LATEST Kevin De Bruyne ‘loves Man City and wants to keep winning’, reveals father targets moving on Bielsa packs his teams with speed and energy, so it’s easy to see why McCarron has caught the eye of Leeds scouts.Edmonsdson added: “At 15 he was blessed with loads of pace, which is why we took a chance on him, but he was a young boy who would get very frustrated very quickly.“As he’s matured and come into full-time football, that’s been the biggest change in him. If he makes a mistake now, his work rate is unbelievable.”last_img read more

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Tactical analysis: Why Aston Villa signing can be a huge hit in the Premier League

first_img 13 TROPHY To fully understand the potential impact Wesley may have this season for Aston Villa we first have to consider the kind of systems that he was used to playing in whilst in Belgium. The shot map for Wesley over the course of the 2018/19 season is also helpful in allowing Villa fans to understand the kind of forward that they have signed.As you can clearly see the clear majority of shots from the forward were concentrated in the penalty area. This will be fine going forward if Villa are able to provide the kind of service that Wesley will thrive from.In a side that struggles for consistent possession and will have to play on the counter-attack, though, the Brazilian will have to be more adept at creating his own chances.  Lampard appears to aim dig at Mourinho for handling of Salah and De Bruyne at Chelsea FAREWELL Here we see the most used formations by Club Brugge over the course of the 2018/19 season. As you can see they spent 73% of their time in either a 3-5-2 or a 3-5-1-1.In each of these systems, Wesley was used to playing with close support, allowing him to combine before moving into the penalty area. Total Football Analysis The biggest market value losers in 2019, including Bale and ex-Liverpool star Man United transfer news live: Haaland ‘wants a change’, two players off in January The heatmap for Wesley last season shows a striker who played inside the penalty area a great deal but who could also drop into deeper positions in order to bring others into play.His ability to hold the ball up and bring other players into play could well be key for Aston Villa as they prepare for life in the top flight. Wyscout Here we see Wesley moving in towards the penalty area as his teammate attacks in the wide-right area.The key in finding space from the forward comes in the way that he originally makes a movement towards the far post, dragging a defender with him, Wesley then changes direction and sprints in front of the covering defender in order to meet the cross at the front post.This type of movement is designed to pull defenders out of position and force them off balance. The forward player can then take advantage of the fact the defenders are not set through quick changes of direction in order to attack either the front post or far post.Wesley is excellent at timing these changes of direction in order to find a pocket of space that he can exploit. We see a similar situation here with the ball this time on the opposite side of the field.On this occasion we see Wesley isolated against a single defender in the middle of the penalty area.The defender, initially, is in a good position and will feel as though he has the threat of Wesley controlled. As soon as the defender turns his attention towards the ball, however, we see the forward take advantage to attack the space.The defender’s attention turns away from Wesley and, as it does, the Brazilian forward bursts past him on his blind side (behind) and attacks the front post. This is an instant cue for the wide player and the ball is played immediately to meet the run of the forward.Aerial AbilityWhile we see the movement from Wesley allowing him to find space in the area and he is a strong finisher with his feet when the ball is on the ground, he is arguably more dominant in the air.The same kinds of movement, occupying the blindside and timing runs across the face of the defensive players, allow him to meet balls played across the face of goal at speed and with excellent timing.Wesley, however, is equally comfortable when challenging defensive players for 50/50 high balls, whether winning headers or simply looking to bring others into play through flick on’s. This is of course an aspect of his game that should go down well in the Premier League. REVEALED 13 One of the players signed by Aston Villa for this coming season is Brazilian forward Wesley who has signed from Club Brugge for a reported £22m.This signing appears to be a clear reaction to the loss of the young English forward Tammy Abraham, who has returned to Chelsea following the end of his loan spell, with Wesley offering a similar playing profile.Both are physically imposing forwards who are capable of leading the line on their own or playing with a second forward alongside them.When we look beyond that, however, we start to see differences between the two. Abraham, despite being younger, has a higher ceiling and is better with the ball at feet. Wesley, on the other hand, is a more instinctive finisher in and around the penalty area at this stage of his career.The Brazilian displays excellent movement and timing in the box. He is especially adept at playing on the blind side of the nearest defender before making late movements that take him into space when the ball is being played into the penalty area. Liverpool update ‘Champions Wall’ after ending 2019 as European and world champions A similar situation here but this time the starting position for Wesley is noticeably deeper.As the ball is progressed into the wide-area we see the ball immediately played inside into the pocket of space that Wesley has occupied.As the ball comes into the Brazilian he does not even take the ball down but immediately plays a volley into the path of a midfielder who is advancing from a deeper line.This pass from Wesley shows his technique and understanding of space as he releases a teammate who is moving into a better position. After playing this pass in the first instance we again see Wesley look to run into advanced areas to enter the penalty area.ConclusionSigning forward players form the Belgian top flight carries with it the same risk as signing them from the Dutch Eredivisie.It can be difficult to accurately judge the level of opposition that they have played against to this point in their career. The first few matches of the season will give us a better indication as to whether Wesley will be able to physically dominate English defenders as he has done elsewhere.Aston Villa have spent and bet big on their return to the top flight. It will be interesting to see whether this strategy is successful in helping them survive and kick on at the Premier League level.If you enjoyed this piece then head over to totalfootballanalysis.com and get a digital copy of their latest magazine for just £4.99 – over 100 pages of pure tactical analysis and coaching content – annual subscriptions also available! 13 New job Wyscout latest 13 As well as a monthly digital magazine you can subscribe to totalfootballanalysis.com for just £2 a month and get over 100 exclusive articles – match analysis, player and team scout reports and much moreIntelligent MovementWhen watching Wesley play, with his side in possession, the first thing that jumps out is that the Brazilian is fantastic with his movement to create space in the penalty area.At the top level of football, the difference between a striker who scores consistently and one who consistently fails to find the net is their movement in the penalty area.Watch Wesley closely and you will often see the forward isolate a defender and then pull away into a pocket of space while the ball is in the wide areas.  Matic one of two players for sale with ‘two Premier League clubs’ interested LATEST FOOTBALL STORIES Wyscout Wyscout 13 13 Arsenal transfer news LIVE: Ndidi bid, targets named, Ozil is ‘skiving little git’ deals Wesley in Champions League action against Borussia Dortmund last season. Now we need to consider the systems that Dean Smith used at Villa last season. As you can see 4-1-4-1 was the most commonly used system although 4-3-3 was used in 25% of the season.The focus for Wesley will be on making sure the two central midfielders are capable of moving into supporting positions when Villa are in possession. Otherwise, we may see Wesley largely isolated.In this tactical analysis, we examine him more closely to show Aston Villa fans what they can expect from their new forward. Getty Images In this example, we see Wesley initially isolated against more than one defender as his team are looking to access the final third.In order to facilitate this the forward drops off the attacking line into a deeper position. This movement allows the ball to be progressed into him and Wesley has the strength and balance to receive the ball and hold off the defensive players.As soon as the ball is played into Wesley however he shifts it backwards at an angle to a supporting player. This immediately changes the angle of attack to catch the defence out as they shift towards Wesley to close the ball down.The forward is then able to spin and move into the penalty area looking for the next pass. Former Crystal Palace and West Brom manager Pardew takes over at Dutch strugglers LATEST Total Football Analysis Wyscout Every year it can be fascinating to follow the strategies used by clubs newly promoted to the Premier League to build their squad.Take this year, for example, as the likes of Norwich City, promoted as champions, have made small alterations and re-signed existing players on improved contracts.Contrast this approach to Aston Villa, who have spent at around the £100million mark, and we immediately see the differences in strategy emerge. 13 Wyscout Liverpool news live: Klopp reveals when Minamino will play and issues injury update Wyscout 13 Wyscout Solskjaer gives Pogba fitness update and calls him world’s best all-round midfielder 13 13 JIBE 13 This time the initial pass comes from a deeper position.It is now a common theme but you can see that Wesley has initially positioned himself behind the covering defender on that players blindside.From this initial position the forward will make eye contact with the man in possession of the ball before making a quick angled run across the face of the defender.He is then free to meet the cross at full pace in space in the penalty area. Once again Wesley gets a headed shot at goal.Linking PlayIn modern football, of course, it is important that a forward player is more than just a penalty box predator. They have to be able to hold the ball up in order to bring others into play and make movements that will drag defensive players out of position.Wesley, as a player who profiles as a traditional target man, is strong when it comes to holding the ball up. He is also underrated when it comes to bringing others into play and linking with midfielders in the attacking phase. His touch and vision allow him to play quickly with one or two touches. 13 Where every Premier League club needs to strengthen in January Wyscout targets boost Wyscout 13 We see once again in this example that Wesley once again times his movements in the penalty area perfectly.With the ball in the wide area on the right-hand side the forward is initially marked by two defensive players. As the ball is about to be played in, however, we see Wesley make a move in front of the front post defender in order to meet the cross and head towards goal. July’s Total Football Analysis magazinelast_img read more

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SPFL dismiss King’s call for chairman to be suspended

first_imgThe SPFL have dismissed Rangers chief Dave King’s demand for an investigation into their chairman Murdoch MacLennan’s business links to Celtic shareholders.Following a media report, King called for MacLennan to be suspended pending an investigation into the alleged non-disclosure of his appointment as a non-executive chairman of Independent News and Media PLC – an Irish media giant part owned by Celtic majority shareholder Dermot Desmond.But the SPFL have refuted the Rangers chairman’s request, insisting that no investigation is warranted as a non-executive position on a PLC board does not create a business relationship between that individual and a minority shareholder in the company.An SPFL spokesman said: “It’s not surprising that Murdoch, having stepped down as deputy chairman of Telegraph Media Group, should be approached by other businesses in that sector. “The members of the SPFL board were each informed of Murdoch’s appointment on January 19th 2018, the same day it was publicly announced in a press release from Independent News & Media PLC.“No director raised this issue subsequently and it was not the subject of any board discussions.“To be definitive, a non-executive position on a PLC does not constitute a business relationship between that individual and a minority shareholder in the company and therefore no investigation is warranted.”last_img read more

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Freeplay: Brand with a conscience

first_img5 March 2007Swedish-based global marketing and branding think-tank the Medinge Group has recognised South African energy efficiency company Freeplay Energy as one of nine worldwide brands with a conscience.Business Day reported last Tuesday that Freeplay Energy is the only South African company to be awarded such a status since the annual Medinge awards began in 2004.Winning companies are cited for their contribution to the betterment of society by sustainable, socially responsible behaviour while also being successful at commercial branding.Even though Freeplay has been listed on the London Stock Exchange since 2005, it continues to develop its products at its Cape Town office that remains the hub of the company’s research and development.The company’s products combine wind-up, solar and rechargeable energy to power a range of products, including radios, torches, headlamps and other illuminating devices, as well as standalone chargers for wireless sets and cellphones.Freeplay Energy’s chairman and co-founder Rory Stear said: “As corporate ethical performance and accountability assume increasing importance in today’s global business environment, this recognition serves as an endorsement of our efforts in both a commercial and humanitarian capacity.”One of the Medinge Group’s directors, Jack Yan, told Business Day that Freeplay Energy was an early nominee for this year’s Brands with a Conscience Award.“In addition to the company’s humanitarian aims, Freeplay Energy products are setting new standards in the sustainable products industry for useful alternatives and portable energy solutions,” Yan said.Life-changing technologyThe technology Freeplay Energy develops plays a huge role in promoting education and access to life-changing information to isolated communities in the developing world.To date, more than 400 000 products, including 200 000 Lifeline radios powered by Freeplay technology, are being used in humanitarian projects in more than 20 countries.In 2006, it entered into an agreement with the United Nations Children’s Fund to supply the organisation with Lifeline radios and provide electoral education in Madagascar.Freeplay Energy was a finalist in the 2005 Walpole British Excellence Awards in the British brand-of-the-year category and was nominated for an award in California’s Tech Museum of Innovation’s health category. In addition, its Cape Town-designed Indigo LED lantern was recognised for its innovation, design and engineering at this year’s Consumer Electronics Show in Las Vegas.SouthAfrica.info reporter Want to use this article in your publication or on your website?See: Using SAinfo materiallast_img read more

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Blue lights could prevent bird strikes

first_imgBird strikes—the collision between birds and aircraft—are among the most common aviation hazards. They destroy planes, kill people, and, in the United States alone, cause an estimated $700 million in damage each year. One possible approach to reducing collisions lies in outfitting planes with warning lights that would help birds notice their approach and avoid a collision, but the differences between human and avian sight—which include a wider color space and higher sensitivity to ultraviolet light in birds—make developing such solutions complicated. Now, researchers have found that blue LED lights (with a wavelength of 470 nm) are the most conspicuous to brown-headed cowbirds, which often collide with aircraft. The scientists fitted lights of this color to a small, remote-controlled model airplane. They then recorded the reactions of cowbirds in cages to this plane—both when stationary and when flying toward the birds—with the lights on, off, and pulsing. The researchers found that having the lights on made the cowbirds five times more likely to exhibit an alert response (such as stretching their necks, raising their heads, or crouching) to the stationary plane than without; the birds were also twice as quick to respond to planes with lights than to planes without lights. Similarly, although the time the birds took to react to the moving plane got slower as the plane’s speed increased, the presence of flashing lights helped the birds react faster than to those without. Based on their results, reported in The Condor, the researchers propose a number of preliminary concepts that could help birds better avoid aircraft—such as runway lights that illuminate in sync with taxiing planes and onboard lights that flash during taxiing and shine continuously during takeoff. Similar approaches could be adapted for stationary obstacles, too—such as skyscrapers or wind turbines—to help reduce collisions.last_img read more

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What’s your risk of kidney disease, heart attack, or diabetes? A single molecule can tell

first_imgNate Henry (right), Nick’s identical twin, is healthy. Nick’s high levels of a molecule called suPAR may explain his illness. The data gets stronger and stronger that suPAR is the worst toxin you can have for the kidneys. Nick Henry first experienced the symptoms of kidney disease in 2004, shortly after the 19-year-old had a severe reaction to a spider bite. “I woke up one morning, and I was just swollen from head to toe,” he recalls. But doctors managed Henry’s disease, allowing him to return to his unusually active lifestyle—including baseball, softball, basketball, flag football, golf, and fishing—in his northeast Louisiana hometown of West Monroe. Shortly after he witnessed the death of his mother in a motor scooter accident in 2012, however, Henry’s renal health took a dramatic turn for the worse. “It’s almost as if my body went into shock,” he says. “Within a couple months, boom, I started swelling up again.”That swelling was a sign that his kidneys were no longer working normally. A biopsy confirmed that he had focal segmental glomerulosclerosis (FSGS), a severe form of kidney disease. In FSGS, the kidney’s glomeruli—the microscopic filtration units that sieve excess fluid and waste products from the blood—become overly leaky; essential proteins such as albumin seep out, disrupting blood chemistry and causing fluid to leak from the blood vessels into tissues throughout the body. Henry’s condition deteriorated so rapidly that by July 2014, his doctors in Shreveport, Louisiana, decided to remove both diseased kidneys. The next month, Henry received a transplanted kidney from his identical twin, Nate, who was healthy, even though FSGS can be genetic in origin.Within a day of the transplant, however, Henry felt like the swelling was coming back. At first, his doctors reassured him that he was doing fine. “Once they checked my urine, saw me spilling a bunch of protein again,” he says, “they realized [FSGS] was attacking the new kidney.” Three days after the surgery, Henry’s doctors conceded that the newly transplanted kidney had already become diseased. His transplant doctor, Neeraj Singh of Louisiana State University in Shreveport, says the recurrence was “one of the most dramatic cases I’ve seen.”Sign up for our daily newsletterGet more great content like this delivered right to you!Country *AfghanistanAland IslandsAlbaniaAlgeriaAndorraAngolaAnguillaAntarcticaAntigua and BarbudaArgentinaArmeniaArubaAustraliaAustriaAzerbaijanBahamasBahrainBangladeshBarbadosBelarusBelgiumBelizeBeninBermudaBhutanBolivia, Plurinational State ofBonaire, Sint Eustatius and SabaBosnia and HerzegovinaBotswanaBouvet IslandBrazilBritish Indian Ocean TerritoryBrunei DarussalamBulgariaBurkina FasoBurundiCambodiaCameroonCanadaCape VerdeCayman IslandsCentral African RepublicChadChileChinaChristmas IslandCocos (Keeling) IslandsColombiaComorosCongoCongo, The Democratic Republic of theCook IslandsCosta RicaCote D’IvoireCroatiaCubaCuraçaoCyprusCzech RepublicDenmarkDjiboutiDominicaDominican RepublicEcuadorEgyptEl SalvadorEquatorial GuineaEritreaEstoniaEthiopiaFalkland Islands (Malvinas)Faroe IslandsFijiFinlandFranceFrench GuianaFrench PolynesiaFrench Southern TerritoriesGabonGambiaGeorgiaGermanyGhanaGibraltarGreeceGreenlandGrenadaGuadeloupeGuatemalaGuernseyGuineaGuinea-BissauGuyanaHaitiHeard Island and Mcdonald IslandsHoly See (Vatican City State)HondurasHong KongHungaryIcelandIndiaIndonesiaIran, Islamic Republic ofIraqIrelandIsle of ManIsraelItalyJamaicaJapanJerseyJordanKazakhstanKenyaKiribatiKorea, Democratic People’s Republic ofKorea, Republic ofKuwaitKyrgyzstanLao People’s Democratic RepublicLatviaLebanonLesothoLiberiaLibyan Arab JamahiriyaLiechtensteinLithuaniaLuxembourgMacaoMacedonia, The Former Yugoslav Republic ofMadagascarMalawiMalaysiaMaldivesMaliMaltaMartiniqueMauritaniaMauritiusMayotteMexicoMoldova, Republic ofMonacoMongoliaMontenegroMontserratMoroccoMozambiqueMyanmarNamibiaNauruNepalNetherlandsNew CaledoniaNew ZealandNicaraguaNigerNigeriaNiueNorfolk IslandNorwayOmanPakistanPalestinianPanamaPapua New GuineaParaguayPeruPhilippinesPitcairnPolandPortugalQatarReunionRomaniaRussian FederationRWANDASaint Barthélemy Saint Helena, Ascension and Tristan da CunhaSaint Kitts and NevisSaint LuciaSaint Martin (French part)Saint Pierre and MiquelonSaint Vincent and the GrenadinesSamoaSan MarinoSao Tome and PrincipeSaudi ArabiaSenegalSerbiaSeychellesSierra LeoneSingaporeSint Maarten (Dutch part)SlovakiaSloveniaSolomon IslandsSomaliaSouth AfricaSouth Georgia and the South Sandwich IslandsSouth SudanSpainSri LankaSudanSurinameSvalbard and Jan MayenSwazilandSwedenSwitzerlandSyrian Arab RepublicTaiwanTajikistanTanzania, United Republic ofThailandTimor-LesteTogoTokelauTongaTrinidad and TobagoTunisiaTurkeyTurkmenistanTurks and Caicos IslandsTuvaluUgandaUkraineUnited Arab EmiratesUnited KingdomUnited StatesUruguayUzbekistanVanuatuVenezuela, Bolivarian Republic ofVietnamVirgin Islands, BritishWallis and FutunaWestern SaharaYemenZambiaZimbabweI also wish to receive emails from AAAS/Science and Science advertisers, including information on products, services and special offers which may include but are not limited to news, careers information & upcoming events.Required fields are included by an asterisk(*)The sudden failure of Henry’s new kidney is a recent chapter in a long-running medical mystery, dating to when kidney transplants became routine in the 1970s. Up to 30% of transplanted kidneys fail in FSGS patients—not because of immune rejection by the body, as doctors first suspected, but because the new organ immediately begins succumbing to the same disease process that ravaged the original ones. As he struggled to cope with that devastating turn of events (and relied on dialysis to stay alive), Henry traveled to Chicago, Illinois, to consult with Jochen Reiser, a kidney disease specialist who is chairperson of internal medicine at Rush University Medical Center there.Ever since he learned about such transplant failures 2 decades earlier, Reiser has been convinced that “there is something in the blood circulating that attacks the kidney. And we were out to catch that.” What he and colleagues claim to have “caught,” in an elegant but still unfolding story of molecular detective work over the past 10 years, is a protein known as soluble urokinase plasminogen activator receptor (suPAR). When Reiser analyzed blood samples from the Henry twins, the results aligned with the message he has been preaching with evangelical fervor for years. Nate, the healthy brother, had relatively low levels of suPAR; Nick’s were high—a driving force, Reiser believes, of his kidney failure. KidneyGlomerulusFunctional unit of kidneyPodocyteGlomerular basement membraneEndothelial cellsuPARsuPAR Slit diaphragmCapillary Chronic kidney disease affects 14% of the U.S. population, with estimates suggesting nearly 600 million people affected worldwide. The disease steadily erodes the kidneys’ ability to filter the blood, often leading to cardiovascular disease and premature death. Kidney disease—which can directly attack the filtration process, as in FSGS, or damage the kidney’s support structure—is particularly insidious because by the time the first diagnostic signs appear, patients have irreversibly “burned off” much of their kidney function. Historically, the leading risk factors have been high blood pressure, diabetes, and African-American ancestry. (Several mutations associated with increased risk are more common in African-Americans.)But research by Reiser and others has dramatically challenged that traditional picture of risk. If suPAR levels are low, people with the high-risk genes are no more likely to develop kidney disease than people without those gene variants, Reiser says. If suPAR levels are high, people are at greater risk of developing the disease regardless of whether they have the mutations.Molecular studies in animals as well as a growing number of analyses of large human populations associating suPAR with kidney disease have bolstered his confidence—and convinced him the disease could be treated by suppressing suPAR. Some other researchers aren’t convinced, noting that several clinical studies found no clear association between suPAR levels and FSGS. But on both sides of the debate there is widespread fascination with suPAR, a ubiquitous, Zelig-like bystander molecule that, at elevated levels in the blood, seems to presage many health calamities, such as heart attacks, diabetes, and premature death. Whatever suPAR’s precise role in kidney disease, the molecule appears to be a potent signal broadcast by an immune system under siege. It is exquisitely sensitive to inflammation, an accelerant for many diseases.”What is inflammation?” asks biochemist Jesper Eugen-Olsen of the University of Copenhagen, a pioneer in suPAR research. “It’s the language of cells. It’s how cells communicate with each other. When something is going wrong, the immune system is activated. It produces suPAR … and suPAR is a voice that just shouts, ‘Get on with it! Something is going on!’”A brash styleIn neither background nor appearance does Reiser conform with the public image of the director of a major metropolitan medical center. His 10th floor office at Rush sits just behind a corridor lined with photographs of hospital administrators going back to the 19th century—stern-faced, all-knowing medical patriarchs. Inside, Reiser, 46, sports a stylish striped blue suit, fashionably stubby beard, red socks, and slick dark hair. Known among colleagues as ambitious and scientifically gregarious, he has been eager to collaborate with anyone interested in exploring suPAR biology, and his brash, full-on style extends to the conspicuous display of large-format books celebrating the history of Aston Martins (he owns one) and Porsches on the coffee table in his office. Describing the speed of data collection for a paper that several years ago ended up in The New England Journal of Medicine (NEJM), he says, “It was like going from zero to 200 in no time,” adding sheepishly, “Car analogy.”Born and raised in the small German village of Remchingen, on the eastern edge of the Black Forest, Reiser got his medical degree and Ph.D. from Heidelberg University and did an overseas residency at Albert Einstein College of Medicine in New York City. Specializing in kidney disease, he went on to conduct research at Harvard Medical School in Boston and became chief of nephrology at the University of Miami Leonard M. Miller School of Medicine in Florida before being hired by Rush in 2012.Reiser’s arrival in the United States in 1999 coincided with renewed interest in solving the mystery of why up to 30% of FSGS patients who receive transplants see the disease recur in the new kidney. Just 3 years earlier, a group headed by Flavio Vincenti, a transplant specialist at the University of California, San Francisco (UCSF), and Virginia Savin, at the Medical College of Wisconsin in Milwaukee, announced a major clue. They reported in NEJM that they had amassed evidence for an FSGS-promoting factor in the blood of transplant recipients who’d experienced recurrences; they couldn’t isolate the exact protein, but when colleagues later injected an extract of such patients’ blood into rodents, the animals’ kidneys became permeable and spilled protein in the urine. That mysterious “permeability factor” became “the holy grail” of the field, according to Sanja Sever, a molecular biologist who studies kidney disease at Massachusetts General Hospital in Boston.While still in Germany, Reiser had trained his research efforts on a unique renal cell called the podocyte (so named because of its amoebic, faintly footlike extensions). That choice turned out to be fortunate. The kidney has about 1 million glomeruli, and in each one, hundreds of podocytes bridge the gap between the bloodstream and the urinary system. Their footlike extensions wrap around capillaries snaking through the kidneys and, along with two other layers of tissue, form a physical mesh of cells, like a three-ply screen door, that allows only small molecules—sodium ions, potassium ions, and metabolic wastes—to pass into the urinary tract. When the podocytes become damaged, however, they essentially lose their architectural integrity. The kidney filters then become leaky, allowing larger essential proteins such as albumin to escape from the blood and pass into the urine.It’s like a coffee filter, Sever says. “If there are holes in your filter, then you get some coffee grounds in your urine.” Podocyte damage can be reversed early in kidney disease. But, she says, “If you keep losing them, there’s a point of no return. … You are basically walking toward end-stage renal disease.” Kevin Beasley Albumin leakage A dangerous immune responseAnimal models suggest immature immune cells in the bone marrow release more suPAR when an organism is under attack. The molecule, an all-purpose marker of ill health, may be directly toxic to the kidney.A HEALTHY FILTERIn each glomerulus, the footlike extensions of cells called podocytes wrap around capillaries, fitting together tightly to create narrow “slit diaphragms.” The slits form a fine mesh that allows only small molecules to escape from the bloodstream into the urine.KIDNEY DISEASE What causes such damage? Reiser suspected that the mysterious blood-borne factor disrupts podocytes through receptor molecules on their cell surface. He focused on one: β3-integrin, a molecule whose activation perturbs the shape and motility of cells. When he looked for the molecular key that turned the lock of the integrin receptor, he discovered that oncologists had already been working on one such protein, urokinase PAR (uPAR), a cell surface receptor that plays a role in cancer metastasis. Reiser became even more intrigued when he learned that uPAR can be cleaved from cell surfaces and circulate in the blood—at which point it becomes a soluble cousin known as suPAR. Maybe suPAR was the mysterious kidney-destroying factor.In 2011, Reiser and colleagues reported in Nature Medicine that in cell culture, suPAR damaged human podocytes through the integrin pathway. The researchers supplemented that evidence with three mouse models showing that rodents with elevated levels of suPAR suffered kidney damage, although sometimes more slowly than in FSGS. With human clinical data suggesting that elevated suPAR levels correlated with the recurrence of FSGS in patients, a picture emerged in which the protein triggers a pathogenic process that ultimately produces holes in the coffee filter, leading to kidney disease.The findings both electrified and polarized the nephrology community. In a commentary for Nature Medicine, Martin Pollak of Harvard Medical School, who studies the genetics of kidney disease, and nephrologist Stuart Shankland of the University of Washington in Seattle described the findings as “paradigm shifting for our understanding of the pathogenesis of FSGS.”But some groups could not find the same clinical association between suPAR levels and recurrent disease in FSGS patients, and other groups questioned the protocol and interpretation of the animal models. And regardless of whether suPAR actually destroys the kidney, many nephrologists thought its levels were not very informative—by the time those specialists saw patients with kidney disease, suPAR levels were already high and offered no prognostic value. With Reiser claiming to have found the “holy grail” even as several groups were reporting discordant results, says one source, “People felt very emotional.”An omen of ill-healthBy that point, another key strand of the suPAR story had emerged in Europe. There, the focus was on the molecule as a potential biomarker for a range of diseases.The first clues came from AIDS patients. In Copenhagen, Eugen-Olsen and others examined blood collected from more than 300 HIV patients in the early 1990s, before life-saving antiretroviral therapies became available. All those patients had died, but a retrospective analysis showed their suPAR levels eerily correlated with disease progression: Higher levels were associated with an earlier death. Eugen-Olsen then spent several years collaborating with a hospital in the West African nation of Guinea-Bissau, testing suPAR levels in patients suspected of being HIV-infected. Again, higher suPAR levels predicted a quicker death among the infected. Surprisingly, however, suPAR also predicted mortality in patients who didn’t have AIDS; many turned out to have tuberculosis. That finding led him to hypothesize that suPAR might be a more general biomarker for chronic inflammation.In 2001, Eugen-Olsen founded the company ViroGates, which began to manufacture a relatively inexpensive test to measure suPAR levels in the blood. With the test in hand, he and colleagues in Copenhagen began to look at collections of blood samples banked in large-cohort prospective studies. In one called MONICA, which monitored healthy members of the Danish population for about 13 years, elevated levels of suPAR were associated with a higher risk of cardiovascular disease, type 2 diabetes, cancer, and premature death. Two other large European populations, enrolled in the Malmo Diet and Cancer Study and the Danish Inter99 Study, showed similar associations.The findings caught the attention of researchers at Emory University School of Medicine in Atlanta who had been looking for new and better biomarkers to predict risk of adverse cardiac events in people with heart disease. The researchers had built the Emory Cardiovascular Biobank with serum from several thousand patients. “We draw blood, and we follow them for years,” says Salim Hayek, a physician and research fellow at Emory. When two of Hayek’s colleagues, Danny Eapen and Arshed Quyyumi, delved into the biobank, they found that higher suPAR levels predicted heart attacks and death, as they reported in the Journal of the American Heart Association in 2014. (At the annual meeting of the American College of Cardiology last month, Hayek presented further evidence from the Emory group, suggesting that suPAR is a better predictor of cardiac events including heart attacks and death than any other biomarker in widespread clinical use.) Nick Henry had a kidney transplant, but his new organ quickly deteriorated, and he spends his nights on dialysis. An organ under attack In one scenario for a severe form of kidney disease, a blood-borne molecule called soluble urokinase plasminogen activator receptor (suPAR) disrupts the organ’s filtration units, or glomeruli, which remove waste and fluid from the bloodstream. Other molecules may intensify this attack. Jochen Reiser has spent years amassing evidence that suPAR mounts a powerful assault on the kidney. Kevin Beasley In addition to serving as an omen of ill health, suPAR seems to be a remarkably sensitive indicator of lifestyle insults. Studies have shown that the protein’s blood levels typically rise with obesity and with smoking. (Eugen-Olsen, an inveterate smoker, confesses that he quits when his suPAR levels rise and resumes when they subside again.) “Just looking at the data,” Hayek says, “clearly the environment is a much larger contributor to suPAR than genetics.”With its links to multiple diseases and environmental stresses, suPAR appears to sit at the nexus of immune signaling, chronic inflammation, and tissue damage. Among the protein’s normal sources are fat cells, immune cells, and endothelial cells, which produce low baseline levels. But a team led by Reiser and David Scadden of the Harvard Stem Cell Institute showed in 2017 that in mice, immature “stemlike” cells in the bone marrow can release a pulse of suPAR when the immune system detects an attack.Reiser believes suPAR is an ancient and unspecific way for the immune system to send urgent signals to the major organ systems when an organism faces a severe challenge from disease or the environment. Kidney damage, he says, is the long-term cost of that vital signaling mechanism. “As one example,” he says, “you get infected, you release more suPAR, you open your kidneys up, and you can dump the big molecules out into the urine. Almost like a primitive coupling of the immune system to vital organs.” In an acute infection, he says, the body urgently needs to flush out bacterial toxins, relatively big molecules. But if that inflammatory signaling becomes chronic, it takes its toll on kidney function—a trade-off that may have been acceptable earlier in human history, Reiser suggests, but is less so now. “If you live 40 years long, you can burn off the kidney this way, no problem,” he says. “If you live to be 80, 90, 100, you might burn off your kidneys too soon.”For Reiser, the Emory cardiac biobank offered a chance to put to rest the notion that high levels of suPAR are simply a nonspecific sign of failing kidneys, not a cause. When he saw the 2014 heart risk paper from the Emory group, he had the obvious question: Could the large databank show whether suPAR levels predicted the onset of kidney disease years later? He immediately fired off an email to Hayek.The Emory-based group quickly agreed to conduct follow-up renal examinations in more than 1300 patients who had no evidence of kidney dysfunction when they enrolled. The team found a strong link between high suPAR levels and the later development of kidney disease. For patients with the highest levels of suPAR, the risk was three times that of patients in the lowest group, and suPAR levels could predict kidney disease up to 5 years before the first symptoms appeared. “The effect was huge,” Hayek recalls.The association was so robust, he says, that when the group first submitted its findings for publication, “the first response we got from [NEJM] was: ‘How is that association so strong? Is that real? Something is wrong with your cohort.’” But after Hayek and Reiser found the same association in a second, unrelated cohort—the Women’s Interagency HIV Study—NEJM published their findings in 2015. “In that paper,” Reiser says, “we could show that suPAR is the strongest risk factor known in healthy people for new chronic kidney disease. Even stronger than hypertension, diabetes, black race—all of these risk factors that are known to be strong. When you adjust for those, suPAR had the strongest risk.”In the latest piece of evidence, published last summer in Nature Medicine, Reiser collaborated with researchers at the African American Study of Kidney Disease and Hypertension, based at Johns Hopkins University School of Medicine in Baltimore, Maryland, to compare the influence of suPAR and two gene mutations known to predispose African-Americans to kidney disease. A study of about 600 participants revealed that if suPAR levels remain low, “no notable differences” in kidney dysfunction were apparent between people who had the high-risk “disease genes” and people who did not. Conversely, high levels of suPAR strongly predicted kidney disease in African-Americans, regardless of whether the individual had the genetic variants.The proof is the cureYet nephrologists are still divided about whether suPAR actually attacks the kidneys—and if so, how aggressively. Doubters point to the conflicting clinical results and the slow progress of kidney damage in Reiser’s mice with elevated suPAR levels. The original 2011 animal and clinical data are “as complete as you can get,” Vincenti says. “But at some point, there has to be independent duplication of that data.”Several unresolved issues might explain the discrepancies. Different forms of suPAR can circulate in the blood, and some variants might be more pathogenic than whole suPAR. And a team led by Minnie Sarwal of UCSF, Dany Anglicheau of Necker Hospital in Paris, and Reiser has shown that in FSGS, a second blood-borne factor, an anti-CD40 autoantibody, works with suPAR to attack podocytes. “Everyone agrees it’s more complicated” than the initial findings in 2011 suggested, Reiser concedes. “But meanwhile, the data gets stronger and stronger that suPAR is the worst toxin you can have for the kidneys.” Bone marrow Jochen Reiser, Rush University Medical Center By Stephen S. HallApr. 19, 2018 , 12:15 PM Rush Production Group V. Altounian/Science What’s your risk of kidney disease, heart attack, or diabetes? A single molecule can tell MonocyteImmature myeloid cellNeutrophilPodocyte lost to urinary space The controversy may not be resolved to everyone’s satisfaction until a human trial indisputably shows that removing suPAR cures or slows the progression of kidney disease. Several groups are trying to develop a monoclonal antibody drug that would remove suPAR from the blood. One such group is Trisaq, a company Reiser and Sever founded in 2011. Vincenti said his group also has developed monoclonal antibodies to suPAR for clinical testing. “I was excited to try it in patients,” he says. “But we could not demonstrate, at least in our samples, that suPAR was a biomarker for either FSGS or recurrent FSGS. [That’s] held it back.”The first human proof may come not from a drug, but from a medical device. Miltenyi Biotec, a company in Bergisch Gladbach, Germany, makes apheresis devices, which remove substances from plasma, and it is developing a technology that would selectively scrub suPAR out of patients’ blood. “The key question,” notes CEO Stefan Miltenyi, “is if suPAR is the cause [of] renal diseases or just a bystander molecule.” Miltenyi hopes to launch a clinical trial in 2019.For FSGS patients such as Henry, who relies on 8-hour overnight sessions of dialysis to stay alive, a breakthrough therapy can’t come soon enough. But suPAR is already beginning to influence clinical decisions. Singh, Henry’s transplant physician, has used suPAR levels to manage the care of several kidney patients. And since 2013, every patient arriving at the emergency department at Copenhagen University Hospital Hvidovre has undergone suPAR testing to help physicians make triage and discharge decisions.Reiser often likens suPAR to cholesterol—a key marker and disease-associated molecule that can be monitored and, perhaps, ultimately controlled. But the main lesson of suPAR, he believes, is cautionary in an age of genomics and personalized medicine. Although a huge amount of attention (and government coin) has been devoted to identifying genes associated with disease, the environment can sometimes trump them. “I think that the gene adds to the risk profile—it’s part of the picture,” he concedes. “But the environment is a way-underestimated modifier that becomes way more important, quite frankly, than the underlying gene event. And this is … a beautiful illustration of exactly that principle.”last_img read more