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Using a powerful gene-editing technique, scientists have rid human embryos of a mutation that causes an inherited form of heart disease often deadly to healthy young athletes and adults in their prime.

The experiment marks the first time that scientists have altered the human genome to ensure a disease-causing mutation would disappear not only from the DNA of the subject on which it’s performed, but from the genes of his or her progeny as well.

The controversial procedure, known as “germ-line editing”, was conducted at Oregon Health & Science University using human embryos expressly created for the purpose. It was reported in the journal Nature.

The new research comes less than six months after the National Academies of Science, Engineering and Medicine recommended that scientists limit their trials of human germ-line editing to diseases that could not be treated with “reasonable alternatives” — at least for now.

In a bid to make the experiment relevant to real-life dilemmas faced by parents who carry genes for inherited diseases, the researchers focused their editing efforts on a mutation that causes inherited hypertrophic cardiomyopathy.

In this genetic condition, a parent who carries one normal and one faulty copy of a the MYBPC3 gene has a 50-50 chance of passing that mutation on to his or her offspring. If the child inherits the mutation, his or her heart muscle is likely to grow prematurely weak and stiff, causing heart failure and often early death.

In diseases where one parent carries such an “autosomal dominant” mutation, a couple will often seek the assistance of fertility doctors to minimise the risk of passing such a mutation on to a child. A woman’s egg production is medically stimulated, and eggs and sperm meet in a lab — a process called in vitro fertilisation. Then embryologists inspect the resulting embryos, cull the ones that have inherited an unwanted mutation, and transfer only unaffected embryos into a woman’s uterus to be carried to term.

In the new research, researchers set out to test whether germ-line gene editing could make the process of choosing healthy embryos more effective and efficient by creating more of them.

In the end, their experiment showed it could. The targeted correction of a disease-causing gene carried by a single parent “can potentially rescue a substantial portion of mutant human embryos, thus increasing the number of embryos available for transfer”, the authors wrote in Nature. Co-author Dr Paula Amato, an Oregon Health & Science University (OHSU) professor of obstetrics and gynaecology, said the technique “could potentially decrease the number of cycles needed for people trying to have children free of genetic disease” if it’s found safe for use in fertility clinics.

Along the way, though, many of the researchers’ findings were scientifically surprising. Long-feared effects of germ-line editing, including collateral damage to “off-target” genetic sequences, scarcely materialised. And “mosaicism”, a phenomenon in which edited DNA appears in some but not all cells, was found to be minimal.

The study’s lead author, OHSU biologist Shoukhrat Mitalipov, called these “exciting and surprising moments”. But he cautioned that “there is room to improve” the techniques demonstrated to produce mutation-free embryos. As for conducting human clinical trials of the germ-line correction, he said those would have to wait until results showed a near-perfect level of efficiency and accuracy, and could be limited by state and federal regulations.

Eventually, Mitalipov said, such germ-line gene editing might also make it easier for parents who carry other gene mutations that follow a similar pattern of inheritance — including some that cause breast and ovarian cancers, cystic fibrosis and muscular dystrophy — to have healthy children who would not pass those genes to their own offspring.

“There is still a long road ahead,” predicted Mitalipov, who heads the Centre for Embryonic Cell and Gene Therapy at the Portland university.

The research drew a mix of praise and concern from experts in genetic medicine.

Dr Richard O. Hynes, who co-chaired the National Academies’ report issued in February, called the new study “very good science” that advances understanding of genetic repair on many fronts. Hynes, who was not involved with the latest research effort, said he was “pleasantly surprised” by researchers’ “clever modifications” and their outcomes.

“It’s likely to become feasible, technically — not tomorrow, not next year, but in some foreseeable time. Less than a decade, I’d say,” said Haynes, a biologist and cancer researcher at MIT and the Howard Hughes Medical Institute.

University of California, Berkeley molecular and cell biologist Jennifer Doudna, one of pioneers of the CRISPR-Cas9 gene-editing technique, acknowledged the new research highlights a prospective use of gene editing for one inherited disease and offers some insights into the process.

But Doudna questioned how broadly the experiment’s promising results would apply to other inherited diseases. She said she does not believe the use of germ-line editing as a means to improve efficiency at infertility clinics meets the criteria laid out by the National Academies of Science, which urged that the techniques only be explored as treatment for diseases with “no reasonable alternative”.

“Already, 50 per cent of embryos would be normal,” said Doudna. “Why not just implant those?”

Doudna said she worried that the new findings “will encourage people to proceed down this road” before the scientific and ethical implications of germ-line editing have been fully considered.

“A large group of experts concluded that clinical use should not proceed until and unless there’s broad societal consensus, and that just hasn’t happened,” Doudna said. “This study underscores the urgency of having those debates. Because it’s coming.”

WASHINGTON — Two months ago, Marcus Hutchins was an “accidental hero”, a young computer whiz living with his parents in Britain who found the “kill switch” to the devastating WannaCry ransomware.

Today, the 23-year-old is in a US federal prison, charged with creating and distributing malicious software designed to attack the banking system.

His arrest this week stunned the computer security community and shines a light on the shadowy world of those who sometimes straddle the line between legal and illegal activities.

Hutchins’ arrest following Def Con in Las Vegas, one of the world’s largest gathering of hackers, delivered “an extreme shock”, according to Gabriella Coleman, a McGill University professor who studies the hacker community.

“The community at Def Con would not admire a hacker who was doing hard core criminal activity for profit or damage — that is frowned upon,” Coleman told AFP.

“But there are people who do security research... who understand that sometimes in order to improve security, you have to stick your nose in areas that may break the law. They don’t want to hurt anyone but they are doing it for research.”

Hackers are generally classified as “white hats” if they stay within the law and “black hats” if they cross the line.

At gatherings like Def Con, “you have people who dabble on both sides of the fence”, said Rick Holland, vice president at the security firm Digital Shadows.

An indictment unsealed by US authorities charges Hutchins and a second individual — whose name was redacted — of making and distributing in 2014 and 2015 the Kronos “banking Trojan”, a reference to malicious software designed to steal user names and passwords used at online banking sites.

Hacker mindset

James Scott, a senior fellow who follows cyber security at the Institute for Critical Infrastructure Technology, said it is sometimes difficult to separate the white hats from the black hats.

The hacker mindset includes “an insatiable need to satisfy their intellectual curiosity”, Scott said. 

“Hackers have that thing, they can’t sleep. It’s persistent and it’s constant and it can drive you nuts.”

Scott said he did not know details of the Hutchins case but that it is possible he wrote code that someone else “weaponised”.

Some friends and collaborators of Hutchins said they found the allegations hard to believe.

“He worked with me on a project in 2014 he refused payment for,” said a tweet from Jake Williams of Rendition InfoSec. “This is incongruous with a black hat writing code for money at the same time.”

Security researcher Andrew Mabbitt tweeted that Hutchins “spent his career stopping malware, not writing it.”

Chilling effect

Regardless of the outcome of the case, some security professionals said the arrest could erode trust between the hacker community and law enforcement.

Coleman said many hackers and researchers already tread carefully in light of the Computer Fraud and Abuse Act, a law that makes it illegal to access a computer system without authorisation and has been roundly criticised by some security professionals.

“The statute is very broad and it can be wielded as a tool against researchers,” Coleman said.

She noted that many in the hacker community are still reeling over the 2013 suicide of activist Aaron Swartz, who was charged under the same law for illegally downloading academic journals.

Hutchins’ arrest “might actually drive certain security researchers further underground”, said John Dickson of Denim Group, a security consultancy.

“I know several security researchers from Europe, whom I consider on the ‘white hat’ side of the house, who will no longer travel to the US to be on the safe side.”

Holland of Digital Shadows added that it may lead to “strains in the security community, and it could make people more circumspect about who they may collaborate with.”

Scott said the arrest may be counterproductive for cyber security because hackers like Hutchins help expose security flaws in order to fix them.

“The establishment needs hackers more than hackers need the establishment,” he said. 

Scott added that Hutchins’ obvious talents could make him an asset for national security instead of a liability.

“I wouldn’t be surprised if a federal agency made him an offer he can’t refuse,” Scott said.

“A guy like that should be at Fort Meade,” he added, referring to the headquarters of the National Security Agency.

PARIS — Deaths due to extreme weather in Europe could increase fifty-fold from an estimated 3,000 per year recently to 152,000 by century’s end if global warming is not reined in, researchers warned on Saturday.

The toll would be especially high in temperate southern Europe, where deaths due to warming are projected to rise from 11 per million people per year to about 700 per million per year, they wrote in The Lancet Planetary Health.

Heatwaves will do most of the damage, claiming some 99 per cent of future weather-related deaths — more than 151,000 of the annual total by 2100 from about 2,700 per year recently.

“Unless global warming is curbed as a matter of urgency and appropriate adaptation measures are taken, about 350 million Europeans could be exposed to harmful climate extremes on an annual basis by the end of this century,” said the report, based on pessimistic global warming forecasts.

The researchers looked at records of weather-related events in Europe — the 28 European Union members plus Switzerland, Norway and Iceland — for a 30-year stretch from 1981 to 2010 — called the “reference period”.

They then compared this to projections for population growth and migration, as well as predictions for future heatwaves, cold snaps, wildfires, droughts, floods and windstorms.

“We found that weather-related disasters could affect about two-thirds of the European population annually by the year 2100,” wrote four European Commission researchers.

This translated to about 351 million people exposed per year, compared to about 25 million per year in the reference period, when it was just 5 per cent of the population.

Exposure means anything from disease, injury and death due to an extreme weather event, to losing a home or “post-event stress”, the authors said.

‘Could be overestimated’

Deaths from heatwaves were projected to increase by 5,400 per cent, coastal floods by 3,780 per cent, wildfires by 138 per cent, river floods by 54 per cent and windstorms by 20 per cent.

Deaths from coldwaves will decline by about 98 per cent, said the team, which is not “sufficient to compensate for the other increases”.

Climate change is responsible for 90 per cent of the additional weather-related deaths forecast for Europe, said the team.

Population growth accounts for the other 10 per cent, along with migration to hazard-prone coastal zones and cities.

For the purposes of the study, the team assumed a rate of greenhouse gas emissions from burning coal, oil and gas, that puts the world on track for average global warming of 3°C by 2100 from 1990 levels.

The Paris Agreement, concluded by 195 nations in 2015, seeks to limit warming to under 2°C from levels before the Industrial Revolution, when fossil fuel burning kicked off.

The researchers also made no provision for additional measures being taken to boost human resilience to weather disasters.

In a comment on the study, Jae Young-lee and Ho-kim of the Seoul National University wrote its projections “could be overestimated”.

“People are known to adapt and become less vulnerable than previously to extreme weather conditions because of advances in medical technology, air conditioning and thermal insulation in houses,” they wrote in a comment carried by the journal.

On Wednesday, a study in the journal Science Advances said South Asia, home to a fifth of the global population, could see humid heat rise to unsurvivable levels by century’s end.

Also this week, researchers wrote in Environmental Research Letters, that rising carbon dioxide levels will dramatically cut the amount of protein in stable crops like rice and wheat in the decades to come.

The new paper, said Paul Wilkinson of the London School of Hygiene & Tropical Medicine, “is yet another reminder of the exposures to extreme weather and possible human impacts that might occur if emissions of greenhouse gases continue unabated”.

It is often said, although jokingly, that computers have a mind of their own. Apparently, they also can feel the heat. The current heatwave, that does not seem to end, is affecting the machines too, not just humans. 

Contrary to server computers and large or corporate data centres, personal computers of all kinds do not necessarily require an air conditioning environment to run. But they still have a threshold that should not be crossed. They are designed to be used at what is called room temperature.

Most manufacturers do not give clear figures but say that as long as the person using the device can withstand the temperature of the room or the place, the device will function safely. It is globally accepted that a low of 5°C and a high of 28°C are the extreme limits that are tolerated, for laptops as well as for desktops. Outside these limits, there is a clear risk of unexpected computer shutdown or even complete failure and breakdown.

It is worth remembering that server computers are operated in rooms that are kept at around 18oC and even 16°C in some cases, in order to prevent failures, and also to extend the useful life of the equipment.

Until now this summer, and in places where there is no A/C, room temperature is close to the 28°C high extreme and sometime gets even higher.

So what happens when computers overheat, and what can the consumer do to address the issue?

Most of the time the machine will automatically shut down, before actual damage to the components is done. The internal temperature of the hottest part can go up to about 70°C safely, while the built-in heat sinks and cooling fans do their jobs to evacuate the excessive heat outside the equipment’s casing. Above this temperature the computer becomes at risk. Applications that show the internal temperature are easy to find and install; they help the user to monitor what really is going inside.

In some cases of overheating the damage is irreversible and the computer is to repair before it can be used again. There are a certain number of precautions and even corrective actions one can take, however.

With some models of computers, the user can reduce the working speed of the processor; it is called the clock rate. Tech-savvy teen-agers and hardcore gamers are familiar with this trick. Reducing the clock rate when the room temperature is too high is a smart thing to do. It is like walking instead of running for a human being. Reducing the clock rate is done by accessing the BIOS when the computer starts. Once the hot period is over you can always get back there and restore the original clock rate.

Another precaution consists of making sure that the computer and all its internal components, mainly the cooling fans and the vents on the sides, are dust-free and no obstructed. This ensures optimum ventilation and often is enough to prevent disastrous overheating.

On some very hot days I have seen people placing a large, full-size desk fan before their laptop, directing the entire air flow steadily to the machine, as they would do it for themselves! Even if this is not the most elegant solution, it works and does the job perfectly, as it typically would reduce the machine temperature by at least 5°C or 6°C degrees, which typically is enough to prevent damage.

A more or less similar but much more elegant and efficient solution consists of buying one of these laptops cooler stands. You would place it under the laptop and its additional cooling fans would greatly help the laptop to evacuate the excessive heat. They are inexpensive, in the range of JD20, virtually silent, and they draw the necessary power very conveniently from one of the computer’s USB ports.

To confirm that hardware of all kinds can feel the heat, and not just laptops and desktops computer, my trusty Android tablet gave up on me the other day because of the heat, albeit temporarily. Because tablets do not have moving parts like real computers you don’t really expect them to overheat. And yet…

After playing Youtube videos non-stop for more than an hour in a room at 29°C, and upon trying to plug the power charger in the tablet, I got a message saying “Device too hot. Unable to charge now. Retry after a while.” I turned it off, gave it 15 minutes to cool off and everything worked fine after that.

The machines are asking for sympathy and understanding.

By Neal Morton 

SEATTLE — For decades, researchers have built a compelling amount of evidence that the earlier you introduce a child to a second language, the stronger his or her bilingual skills will be.

An infant’s brain also appears to benefit from early exposure to two languages. Earlier this year, for example, a team at the University of Washington used neuroimaging to show that bilingual 11-month-olds demonstrated stronger activity in areas of the brain associated with problem solving and self-control.

So when the regional government in Madrid, Spain, decided to boost bilingual education for infants there, officials asked the UW’s Institute of Learning & Brain Sciences to develop and test a programme to teach a second language to young children whose parents speak only one. 

“There’s a slew of studies that 0-to-3 years is the best time to develop [a baby’s] language skills… but the question is: ‘How do you do that?’” said Naja Ferjan Ramirez, a researcher at UW who helped design the programme and co-authored a new report on its findings.

In 2015, Ferjan Ramirez and co-author Patricia Kuhl, also at the institute, designed the study to answer that question. The researchers, backed in part by funding from the Madrid government, selected 16 students from UW that they trained over two weeks before sending them to Spain. A total of 250 children, ages seven to three months, were then split into two groups: Those who received daily, hour-long English tutoring sessions for 18 weeks, and those who remained in an existing bilingual programme.

The children in the first group spent their time in small groups of 12 with four of the UW tutors, who encouraged them to talk more in English, even if it was just babbling. The tutors also used social, play-based activities and spoke to the children in a way that helps language development.

In the bilingual programme, children spent about two hours a week with an instructor who introduced simple English vocabulary and phrases in a typical classroom setting, with a higher student-teacher ratio.

The parents of both groups were asked not to provide additional English tutoring through the duration of the programme.

At the end of the experiment, the researchers found that, on average, the tutored children spoke in English five times as often in a given hour than those who remained in the existing programme. The tutored children also produced more complex sentences in English and, even 18 weeks after the programme ended, retained their English skills.

“We wondered… if this was just a short-term thing,” Ferjan Ramirez said. “It was a bit surprising that they had actually maintained what they learned.”

Another surprise: The gains were the same for children from low-income neighbourhoods and those from more well-off schools.

Ferjan Ramirez noted many studies have shown children in low-income areas typically have a harder time developing language skills.

But her study suggests that might be due to lack of opportunity to learn. “If you offer children from low socioeconomic status the right kind of method and teach them by the right kind of approach, they can learn to the same extent as children from mid-income neighbourhoods,” Ferjan Ramirez said.

In their report, the researchers acknowledge that smaller class sizes, highly-motivated tutors and other variables could have influenced the study’s results. They also said follow-up studies could look at the impact of longer-term tutoring programmes and what parents can do at home to help develop their children’s foreign language skills, even if the parents speak only one language. 

In fact, Ferjan Ramirez said her team already is trying to adapt the Madrid programme for families in Washington state and the rest of the United States. “If it works for Spanish-speaking children in Madrid, there’s no reason to think it wouldn’t work for children in the United States,” she said.

MUMBAI — Three Indian actors sharing a surname have ruled Bollywood box offices across three decades, but the success of wrestling blockbuster “Dangal” means it is Aamir who’s currently king of the Khans.

Known as the “Khans of Bollywood”, Aamir, Shah Rukh, and Salman have been the undoubted superstars of the Hindi film industry since the mid-1990s, taking it in turns to reign supreme.

But with “Dangal” smashing records, Salman suffering a rare flop and Shah Rukh without a major hit in four years, the crown for now is firmly placed on Aamir’s head.

“The Khans used to be on a par but Aamir has moved ahead and Shah Rukh is kind of lagging behind recently,” film trade analyst Ramesh Bala said of the trio who all turn 52 this year and who are not related.

“Dangal” has set new and previously unimaginable parameters for the box office potential of a Bollywood movie since it was first released in India in December last year.

It quickly became the highest-grossing Bollywood film ever, knocking another of Aamir’s movies off the top spot, and has made close to 20 billion rupees ($310 million) worldwide.

Khan plays the role of wrestling coach Mahavir Singh Phogat who defies the odds by raising his daughters Geeta and Babita Phogat to become champion wrestlers. Geeta won gold for India at the 2010 Commonwealth Games while Babita topped the podium at the 2014 edition.

Critics say the movie resonated because it was a patriotic story about a triumphant underdog that dealt with India’s skewed attitude towards girls, and credit a large part of Aamir’s success to his careful choosing of movies with a message.

“Aamir is one person who really puts a lot of thought and effort into selecting films that are relevant to an Indian audience. There are very few actors who really do enough of that,” film distributor Akshaye Rathi told AFP.

Audiences lapped up Aamir’s 2014 satirical science fiction comedy “PK”, number two on the all-time Bollywood grossing list, for its questioning of religious superstitions.

His 2009 hit “3 Idiots” appealed for its coming of age tale about students struggling to deal with the pressure of becoming engineers.

‘Genius’

Rathi also points to the fact that Aamir does one film every two years on average, while Salman and Shah Rukh regularly release two a year.

“Aamir has been very consistent for a very long time. He doesn’t do as many films as Shah Rukh or Salman and the more films you do the higher the chance that one misses,” Rathi explained.

Salman’s annual Eid holiday release is usually a blockbuster shoo-in, but the latest, “Tubelight” bombed.

Critics panned the script and said the star’s portrayal of a “village idiot” failed to resonate with his largely young Indian male fan base.

Bala blames Shah Rukh’s failure to register a hit since “Chennai Express” in 2013 on “experimenting with different genres”, including romance, action and drama.

Aamir is lauded for taking on challenging roles. For “Dangal” he gained and then lost again 25 kilogrammes in weight while cinemagoers adored his portrayal of a humanoid alien stranded on Earth in “PK”.

“As a star he doesn’t enjoy so much of a fan following as he enjoys the trust of the audience for his craft. People believe at the back of their minds that if Aamir appears in a film there will be something, different, something novel in it,” said Rathi.

“Dangal” has made around $180 million more than “PK” in global sales thanks to a record-breaking run in the hugely profitable Chinese market, where Aamir has worked hard at building his brand, becoming the biggest Indian star there.

“Aamir has time and again proven his marketing genius and his genius when it comes to choosing the right script, delivering a terrific performance and enthralling the audience,” said Rathi.

In India, unlike many other countries in the world, there is no social stigma attached in announcing loudly that you want to go to the toilet. Nobody uses fine terminology like ‘I am going to powder my nose’, or ‘he is answering the call of nature’ or ‘she is washing her hands’ as euphemisms for visiting a lavatory. In fact, there was a phase when all the people from Bollywood, our celebrated film industry, were found for long periods in their respective bathrooms. Whenever you called them on the phone, that is.

These days one sees photographs of film stars splashed all over the social media, carrying a fancy cell-phone in their hands that whenever it rings, they presumably answer themselves. But before the introduction of the mobiles, all of them had landline connections that were handled by other people, like their assistants, butlers or man Fridays. And the most popular response to any phone call was ‘Sorry, Sir is in the bathroom’ or ‘Madam can’t talk to you right now, she’s in the bathroom’. 

If one was persistent, more details would emerge about the actors like ‘Sir is taking a shower’, or ‘Madam is having a bath’. Even if you did not want to know the specifics about where exactly they had reached in his/her grooming ritual, you were provided it anyway. 

In one particular instance, I called up this celebrity that I was supposed to interview for a newsmagazine daily, for an entire week, on the number that was provided to me by his agent. It was picked up every time after the first few rings. The voice on the phone was always courteous and greeted me politely. But I was never connected to the person I wanted to speak to because, you guessed it right. He was constantly in the bathroom! So permanent was his presence there that I was convinced that he suffered from constipation, running stomach or other types of Irritable Bowel Syndrome. I mean, why else would he prefer to be cooped up in his toilet for such lengthy intervals? Either that or he was a compulsive bather, who can tell? 

It is documented that the Tudor monarchs had company even when they visited the lavatory. The ‘groom of stool’ was the person who attended to the Sovereign and he was an important man whose office was highly prized. He spent more time alone with the Ruler than anyone else and very often became his most trusted confidant. This regular access gave him great power.

King Louis XIV’s toilet was designed to look like another throne which he supposedly used while conducting court sessions. A replica of this can be viewed at the International Museum of Toilets, an unusual collection of bizarre loos from down the ages, in New Delhi. It contains hundreds of ancient specimens from across the globe, including a French one that is disguised as a bookcase. The vast assortment of commodes and bidets has been curated to mark the history of sanitation. 

Running late for a meeting recently, I impulsively decide to adopt the toilet manners of our famous Bollywood stars. 

“Your phone is ringing,” my husband calls out. 

“Who is calling?” I ask.

“Blogger Dellybelly,” he reads out the caller identity. 

“Please tell him I’m in the bathroom,” I instruct. 

“But you are not there,” he protests.

“Just say it, will you?” I dictate. 

“Hello, sorry my wife is in the bathroom,” my spouse improvises reluctantly.

LOS ANGELES — An unlikely battle emerged at the box office this weekend between “The Emoji Movie” and “Dunkirk”. As of Saturday morning the animated feature and war epic seemed to be in a dead heat. But by Sunday morning, most of the dust had settled, and “Dunkirk” will once again be the weekend’s first place film.

Christopher Nolan’s latest from Warner Bros. over-performed last weekend when it opened to over $50 million, showing that the director, combined with positive critical reception, still has a strong draw — even for a movie lacking movie star power, and at risk of being written off as yet another World War II movie. This time around it looks to take in $26.6 million from 3,748 locations, for a strong hold.

It is the first time that a movie has been first place two weekends in a row since the same studio’s “Wonder Woman” in early June. Patty Jenkins’ movie has had a phenomenal run since, and is currently closing in on $400 million domestic (right now it’s at $395.4 million).

That means Sony’s “Emoji Movie” is in second for the weekend with $24.5 million from 4,075 locations. The animated adventure took a lot of heat from critics — reaction ranged from meh to horrible, earning its current Rotten Tomatoes score of 8 per cent. Its B CinemaScore is also quite low for an animated movie, meaning audiences are not particularly enjoying the movie either.

T.J. Miller plays the central character, a “Meh” emoji who has “no filter”, meaning his expression can change. The same cannot be said for the rest of the cast, which includes James Corden, Anna Faris, Maya Rudolph, Christina Aguilera, and Sofia Vergara. Oh yeah, and Sir Patrick Stewart plays “Poop”.

“We’re thrilled,” said Sony’s marketing chief Josh Greenstein. “The audience has spoken and made the ‘Emoji Movie’ a family event.”

That leaves this week’s other major release, “Atomic Blonde” somewhat straggling. Focus Features and Sierra/Affinity is looking at a decent, but slightly below expectations launch for the Charlize Theron-starrer with $18.3 million from 3,304 locations. Earlier in the week “Blonde” was pegged at $20 million, but the opening weekend result is still solid considering its $30 million budget. It is also one of the largest launches for Focus, behind only “Insidious Chapter 3” ($22.7 million); “London Has Fallen” ($21.6 million); and “Burn After Reading” ($19.1 million).

The R-rated spy thriller has been compared to a female “Bond” or “John Wick”. After all, it shares DNA with the latter in stuntman-turned-director David Leitch, who will next helm the “Deadpool” sequel. “Blonde’s” launch is bigger than the first “Wick”, which opened in Fall 2014 to $14.4 million, but less than its sequel ($30.4 million).

In “Blonde”, Theron plays a hardcore action star — the type of character that knocked out audiences in “Mad Max: Fury Road” — named Lorraine Broughton. The rest of the cast includes James McAvoy, John Goodman, and Sofia Boutella.

“We’re very happy with the opening. I feel this movie is going to have legs to it,” said Lisa Bunnell, distribution chief at Focus Features.

Bunnell also pointed to Focus’ commitment to putting women in and front and behind the camera with recent releases including “The Beguiled” and “The Zookeeper’s Wife.” “There’s always a thought process behind ‘Let’s see some diversity,’” she said. “This is definitely a movie where Charlize takes centre stage... she can fight men, and she can beat men, so it’s a really empowering movie to go see.”

“Blonde” landed just below the summer comedy event that “Girls Trip” has become. Universal’s release is posting $19.6 million during its second weekend from 2,648 theatres, for only a 37 per cent drop from last weekend. Conversely, EuropaCorp and STX’s “Valerian and the City of a Thousand Planets” flopped last weekend, and is falling off fast. This weekend, Luc Besson’s epic domestic dud made $6.4 million from 3,553 locations. Sony’s “Spider-Man: Homecoming” is hanging in the top five with an additional $13.3 million this weekend.

Annapurna showed Kathryn Bigelow’s “Detroit” at 20 locations before its wide rollout next weekend. From those theatres, the critically approved crime drama took in $365,455 for a per screen average of $18,273.

“We’re seeing that first and foremost, people are really into the movie,” said Annapurna’s distribution head Erik Lomis, who pointed to strong exit information, including 71 per cent of the audience marked “definite recommend”. “It’s a Kathryn Bigelow film, so it’s for everybody,” he added.

To treat the bigger picture, this weekend is not good news for the summer box office overall, which is now 8.1 per cent behind last year.

“We have been in a major struggle to compare favourably with last year’s summer season week after week and with yet another ‘down’ weekend on the books, the summer deficit just added another percentage point in the wrong direction,” said Paul Dergarabedian, senior media analyst at ComScore, who pointed out that this weekend’s crop could not compete with 2016’s “Jason Bourne” and “Bad Moms”. Looking ahead, the first weekend in August seems to signal even more gloom and doom, as several films will be measured up against “Suicide Squad’s” record-breaking August 2016 tally.

SAN JUAN — Something unusual is happening in La Perla, a poor barrio clinging to a steep hillside between Old San Juan and the sea where the video for the pop hit “Despacito” was filmed.

“The gringos are coming!”

Outsiders were afraid to venture in before, but since Luis Fonsi and Daddy Yankee’s megahit, tourists from all over the world are descending on the narrow streets that wind among La Perla’s brightly coloured houses.

“Despacito?” they inquire.

And the barrio’s residents obligingly point out the locations where the video was filmed: the rocks facing the sea where Fonsi sings the refrain, the sea wall where ex-Miss Universe Zuleyka Rivera strolls, the little plaza where men play dominoes — the tables and chairs just as they were in the video.

With the video on the verge of becoming the most watched on YouTube (2.9 billion visits since January, fast approaching the 2.98 billion record held by Wiz Khalifa’s “See You Again”), a barrio once burdened with a bad reputation is now a tourist hot spot.

“I totally came for the tourist video,” said Jennifer Adams, a 28-year-old middle school teacher from North Carolina. “I’ve seen the music video many times and I knew where I needed to go, I got pictures, I tried to dance.”

As for Rivera’s sexy walk by the sea, she laughed and said, “I tried.”

Her goal now is to learn the song’s lyrics so she can sing it in karaoke.

Meanwhile, a Swedish woman took photos of herself in front of Luis’s rocks and a Moroccan tourist ambled along “Despacito coast” — as the area around the sea wall has come to be known in tourist brochures.

In a recent interview, Fonsi marvelled at the song’s impact on the non-Spanish speaking public.

“The language doesn’t matter,” he said. “What’s important is the flavour, the rhythm, the music.”

‘No monster here’

The video’s director, Carlos Perez, said Fonsi and Daddy Yankee “had a very clear vision of what they wanted”.

“The key words were culture, sensuality, colour and dance. What we did in essence was to go film in a barrio that had the qualities that supported what we wanted to do,” Perez said.

“But the evolution of La Perla begins and ends in La Perla.”

In fact, residents’ efforts to improve their barrio are independent of “Despacito.” 

The song’s success is a welcome coincidence that “fell from the sky,” said community board president Yashira Gomez.

Old San Juan, with its cobbled streets and colonial buildings, sits on a hill on a walled peninsula. 

The little houses that make up La Perla are clustered on the other side of the wall, where the sea crashes against the rocks.

Its residents have fought tooth and nail to preserve it, and artists like Calle 13, Ismael Rivera and Ruben Blades have dedicated songs to it.

With 1,600 inhabitants, it is one of the poorest communities in San Juan. Drug trafficking largely drives its economy, with the government trying in vain to clear it.

On Yelp, reviewers comment on the dangers outsiders risk going there.

“Please don’t go there! It is NOT SAFE!” wrote user Gaby G in a three-year-old posting.

But that is changing thanks to the efforts of the community, which set up a communal baker, cultivated two vegetable gardens and raised $80,000 from private donors to paint 402 houses in vivid colours this year.

“They always said it was a dangerous barrio because we’ve been saddled with a history that wasn’t the best,” said Gomez.

“But now you can go in and see that nothing will happen. There is no monster here, no bogeyman, nobody is going to kill you, nobody is going to mug you.”

As she spoke, the community board’s vice president, Lourdes Lopez, showed a group of tourists around. Later, she explained that the community’s next project is to set up a small business offering guided tours.

Hotel occupancy in May rose 9 per cent compared to the same month last year, but there are still no overall figures to confirm the impression that tourist visits are up, said Jose Izquierdo, executive director of the government’s Puerto Rico Tourism Company.

Puerto Rico hosted 1.7 million tourists in 2015, 6 per cent of its total GDP, according to the US Senate Finance Committee.

But even when official figures are available, statistics will not say how many specifically came for the “Despacito” experience. A bump could also be attributable to the end of last year’s Zika crisis.

But Izquierdo is sure that “Despacito” enhanced the island’s brand recognition.

“All the elements are in place for Puerto Rico to top the list for travellers seeking a Caribbean destination,” he told AFP.

And that is good news for the US territory, which has been hard hit by a financial crisis that resulted in bankruptcy in May.

Marwan Badran, Hotels.com’s manager for Latin America, said online searches for hotel rooms in Puerto Rico shot up 45 per cent this year.

“We often see spikes upwards for locations of hit movies or TV series and celebrity weddings,” he said.

“Puerto Rico is no different now that Despacito has become the world’s most streamed song in history.”

Sister to Audi’s petrolhead-favourite RS6 Avant super-estate model, the RS7 is the Ingolstadt manufacturer’s low-slung, luxurious and dramatic answer to the Mercedes-AMG CLS63 and fellow competitor with the BMW M6 GranCoupe and Porsche Panamera Turbo.

If less practical than the RS6’s family wagon body style, the RS7’s low and rakishly descending coupe-like body, however, appeals to a broader audience of high performance luxury car buyers. 

Powerful enough in regular 552BHP guise, the driven RS7 Performance, however, turns up the power event further, with an additional 45BHP and 37lb/ft torque, and cuts 0-100km/h acceleration by 0.2-seconds.

Low-slung and assertive

Beating the Lexus GS-F to take the 2017 Middle East car of the Year awards’ Best Midsize Premium Performance Sedan category, the RS7 Performance’s body style could, however, be described as a more practical liftback design, with its rear hatch lifting up to provide better access to a generous 535-litre boot that is the case for a traditional saloon body. 

And as a luxurious, high performance, coupe-like 5-door with plenty of premium cache, one could also view the RS7 Performance as somewhat of an indirect competitor to more powerful versions of the electric-powered Tesla Model S, with which it shares a similar body style, weight and size.

Slightly lower and longer than its RS6 sister, the RS7 shares a similarly assertive fascia, with vast honeycomb hexagonal single-frame grille, surrounded by strongly browed and slim LED headlights and bide hungry side intakes.

A moody and dramatic design with deep-set rear lights, muscular haunches and chiselled and ridged bodywork, the RS7 performance features defined wheel-arches and again, huge alloy wheels, twin integrated tailpipes, sharp edged air-splitter style lower front bumper lip and level waistline that emphasises its Quattro four-wheel-drive. The Performance is distinguished by matt titanium exterior details and is available in Ascari blue paint, exclusive to this more powerful version.

Vicious and versatile

No slouch in standard guise, the RS7 is already a brutally powerful performer capable of blasting through the 0-100km/h benchmark in just 3.9-seconds, however, the RS7 Performance unleashes yet more power and performance from the same 4-litre direct injection twin-turbocharged V8 engine. Intense and abundant, the RS7 Performance develops ekes out a tremendous 597BHP at 6100-6800rpm from its comparatively small V8 engine, and the same 516lb/ft torque but over a wider 1750-6000rpm band.

However, for short bursts on overboost, torque output rises to a 553lb/ft peak throughout 2500-5500rpm. Altogether, this reduces 0-100km/h acceleration to a supercar-rivalling 3.7-second time, while top speed can optionally be de-restricted to 305km/h.

Meanwhile seamless cylinder de-activation and stop/start system yields restrained and unchanged when driven modestly.

With turbochargers positioned for short intake gas flow path piping and responsive quick-spooling turbos, the RS7 Performance almost eliminates turbo lag, and with Quattro four-wheel-drive ensuring tenacious traction, it is able to launch from standstill with staggering immediacy. 

Pulling with volcanic urgency throughout its rev range when driven with intent, the RS7 Performance remains responsively effortless even when cruising in high gears. Its acoustics include bass-heavy mid-range burbling, bellowing top-end and a crackle on lift-off and gear changes from hard throttle inputs. Meanwhile seamless cylinder de-activation when cruising and a stop/go system help the RS& Performance achieve 9.6l/100km combined fuel efficiency, which given its prodigious performance and 1930kg mass, is very much restrained.

Adjustable and agile

Resolutely stable at speed and indefatigably confident in getting there, the RS7 Performance is driven through a crisp, quick and smooth shifting 8-speed automatic gearbox, with the many ratios allowing for responsive performance and economic cruising. 

Featuring numerous and individually adjustable driving modes for steering, damping, engine, gearbox, exhaust and sport differential, the RS7 can be tailored to be tauter, more responsive and vocal, or more comfortable, smooth and relaxed. Whether in light resistance Comfort mode or meaty Dynamic, steering features excellent directional stability at speed and is precise through corners, if not textured with much road feel. Meanwhile brakes are highly effective and fade-resilient.

With Quattro four-wheel-drive allocating 60 per cent power rearwards and able to vary the split between 70 per cent frontwards and 85 per cent rearwards, the RS7 Performance seemingly defies its front-biased weight distribution, with its engine positioned just ahead of the front axle.

A limited-slip differential further distributing power left and right as necessary, and a torque vectoring system that brakes the inside wheel through corner additionally enhances the RS7 Performance’s agility and eager, tidy turn-in. With phenomenal traction and grip, the RS7 Performance takes fast corners in its stride, while eventual understeer can be kept at bay by its stability systems or by simply easing off the throttle.

Refined and reassuring

Brutally effective through corners, the RS7 Performance sticks to the road like glue and if one forces the rear out, its four-wheel-drive quickly claws back traction. Meanwhile, adjustable adaptive air dampers provide taut flat body control through corners in dynamic mode, with tauter better body control in “dynamic” mode, and a more forgiving ride in ‘comfort’ mode. 

Firm and busy on imperfect surfaces in “dynamic”, the RS7 performance’s default “auto” mode actively changes damper settings. Reassuringly planted at speed, the RS7 Performance is a natural continent-cruncher, and is settled and buttoned down over crests and dips and on rebound.

Well equipped and refined inside, the RS7 Performance is both distinctly sporty yet luxurious, and features sophisticated sound cancellation, acoustic window lamination, frameless windows and optional massaging front seats. 

The RS7 Performance features supportive, well-adjustable and comfortably body-hugging sports seats, while layouts are logical, textures soft and materials include good quality leathers, carbon-fibre, metal and Alcantara rooflining. Spacious in front and with practical lift-back boot, the RS7’s rear headroom and side rear visibility is not as generous as the estate body RS6. 

Equipment includes 360° camera for improved manoeuvrability, intuitive infotainment system with 4G Wifi connectivity, numerous driver-assistance systems and a comprehensive range of creature comforts and gadgets.

TECHNICAL SPECIFICATIONS

Engine: 4-litre, twin-turbo, in-line V8-cylinders

Bore x stroke: 84.5 x 89mm

Compression ratio: 9.3:1

Valve-train: 32-valve, DOHC, direct injection

Gearbox: 8-speed automatic

Ratios: 1st 4.714; 2nd 3.143; 3rd 2.106; 4th 1.667; 5th 1285; 6th 1.0; 7th 0.839; 8th 0.667

Reverse/final drive: 3.317/3.076

Drive-line: four-wheel-drive, self-locking centre differential, optional limited-slip rear-differential

Power distribution, F/R: 40 per cent/60 per cent

Power, BHP (PS) [kW]: 597 (605) [445] @6100-6800rpm

Specific power: 149.5BHP/litre

Power-to-weight: 309BHP/tonne (unladen)

Torque, lb/ft (Nm): 516 (700) @1750-6000rpm

Torque, lb/ft (Nm), overboost: 553 (750) @2500-5500rpm

Specific torque: 187.8Nm/litre (overboost, unladen)

Torque-to-weight: 388.6Nm/tonne (overboost)

0-100km/h: 3.7-seconds

Top speed, restricted/de-restricted: 250/305km/h

Fuel consumption, urban/extra-urban/combined:

13.3-/7.3-/9.5-litres/100km

CO2 emissions, combined: 221g/km

Fuel capacity: 75-litres

Wheelbase: 2915mm

Track, F/R: 1634/1625mm

Overhangs, F/R: 960/1137mm

Headroom, F/R: 1028/944mm

Aerodynamic drag co-efficient: 0.30

Luggage volume, min/max: 535-/1390-litres

Unladen/kerb weight: 1930kg/2005kg

Steering: Electric-assisted rack & pinion

Turning Circle: 11.9-metres

Suspension: Multi-link, adaptive air dampers

Brakes: Ventilated & perforated discs

Tyres: 275/30ZR21