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比流感更可怕的神秘病毒竟然有这么多

The mystery viruses far worse than flu
比流感更可怕的神秘病毒竟然有这么多

Spanish flu was one of the most serious pandemics humanity has faced over the last century. But there are others, and some have the capacity to be even deadlier.

西班牙流感(Spanish flu)是过去一个世纪以来人类面临的最严重的流行传染病之一。但还有一些传染病甚至更致命。

It arrived with the army of England’s new king. Just days earlier, tens of thousands of men had been fighting for their lives on a marshy field in Bosworth, Leicestershire. There, in the summer of 1485, the bitter rivalry between Henry Tudor and Richard III was finally resolved – with Richard III dying at the Battle of Bosworth Field.

这种疾病随着英格兰新国王的军队一起到来。几天前,成千上万的人在莱斯特郡(Leicestershire)博斯沃思(Bosworth)的沼泽地里奋战。1485年的夏天,亨利·都铎(Henry Tudor)和理查三世(Richard III)之间的激战终于见分晓——理查三世在博斯沃思原野战役(Battle of Bosworth Field)中阵亡。
 

Freshly styled as Henry VII, the victor led his troops on to London. Little did he know that there they would be about to face a very different kind of mortal peril.

刚登基为亨利七世(Henry VII)的胜利者亨利·都铎率领他的部队意气风发地进入伦敦。他不知道的是,他们即将面临另一个与战场完全不同的致命危险。

The first sign was a feeling of general apprehension, which soon led to shivers, pains, and headaches. Then the perspiration set in. The victims would be swamped by a torrent of sweat, which led to insatiable thirst and delirium. Finally, they’d feel an overwhelming urge to sleep. If they succumbed, they’d likely end up dead. The fatality rate was up to 50%.

此病最初的症状是一种莫名的紧张不适,很快开始寒颤、疼痛和头痛,然后开始出汗。患者出汗量很大,从而导致极度口渴和精神错乱。最后,他们会感到极度嗜睡。如果没能扛住,最终可能会死亡。此病死亡率高达50%。

The army had brought with them a strange and unknown disease. Dubbed “The English Sweat”, this alarming malady swept across the city, killing 15,000 people in just six weeks. Eventually the epidemic fizzled out, but not before it had spread to Europe, leaving plenty of mourners in its wake.

亨利七世军队带来的是一种奇怪且未知的疾病。这种令人惊恐被称为“英国汗热病”(The English Sweat) 的瘟疫席卷伦敦,短短6周就导致15000人丧命。虽然瘟疫最终销声匿迹,但在此之前曾蔓延到欧洲,留下大量失去亲人的哀悼者。

And it kept coming back – the disease’s reign of terror continued through the next generation of Tudors, striking four more times over the coming century.

疾病的阴影一直持续到都铎王朝的下一代,在下一个世纪惊人地爆发了四次。

Henry VII’s son, Henry VIII, was petrified. During one particularly devastating outbreak, he slept in a different bed every night, presumably hoping to outmanoeuvre it. Here was a disease that could strike out of nowhere, often leading to death in a matter of hours; one chronicler wrote that you could be “merry at dinner and dedde [sic] at supper”. Even more uneasily, it seemed to have a peculiar affinity for the nobility. It killed many people at court, and nearly cut short the King’s romance with Anne Boleyn.

亨利七世的儿子亨利八世(Henry VIII)被吓坏了。在一次特别毁灭性的爆发中,他每晚睡在不同的床上,大概是想以此躲过瘟疫。这是一种可能在任何地方突然爆发的传染病,通常几个小时内就能致人死亡;一个记录者写道,你可能“晚餐时还很愉快,夜宵时就死了”。更让人不安的是,这种传染病似乎格外青睐贵族,导致宫廷里许多人死亡,还差一点就终止了国王与王后安波琳(Anne Boleyn)的风流韵事。

To this day, no one has any clear idea what caused the mysterious English Sweat. But the leading theory is that this mega-outbreak wasn’t caused by the flu, Ebola, or any of the infamous diseases we often hear about.

时至今日,没有人清楚是什么导致了这种神秘的英国汗热病。但主导理论认为,该病的大爆发不是由流感(flu)病毒、埃博拉病毒(Ebola)、或任何我们经常听到的臭名昭著的病原体引起的。

Instead, the culprit was a type of hantavirus – a rare family of viruses that typically infect rodents.

其罪魁祸首是汉坦病毒(hantavirus),属於一种罕见的病毒科,通常经啮齿类动物传播。

Not all pandemics are caused by the obvious suspects. Though the media have us whipped up into a frenzy over a select cast of superstar pathogens, the villain in the next global drama may be lurking in the unlikeliest of places; perhaps it hasn’t even been discovered yet.

并不是所有的流行病都是由明显的怀疑病原体引起的。尽管媒体煽动我们迁怒于一些被挑选出的臭名昭著的病原体,但下一次传染并全球大爆发的元凶,可能潜伏在看似最不可能的地方,甚至也许还没有被发现。

“I think the chances that the next pandemic will be caused by a novel virus are quite good,” says Kevin Olival, a disease ecologist from the EcoHealth Alliance, a US-based organisation that studies the links between human and environmental health. “If you look at Sars, which was the first pandemic of the 21st Century, that was a previously unknown virus before it jumped into people and spread round the world. So there’s a precedent there – there are many, many viruses out there in the families that we’re concerned with.”

生态健康联盟(EcoHealth Alliance)的疾病生态学家奥利瓦尔(Kevin Olival)说:“我认为下一次大流行病很可能由一种新型病毒引起,如果你看看非典(Sars,也翻译为沙士),这个21世纪的第一场流行病,在进入人们视野蔓延全球之前,是一种人类从未听说过的病毒。所以是有先例的——这些病毒群里有许许多多另我们担心的病毒。” 生态健康联盟总部位于美国,专研究人类和环境健康之间的联系。

Olival is not alone. Earlier this year, Microsoft co-founder Bill Gates warned that the next pandemic could be something we’ve never seen before. He suggested that we prepare for its emergence as we would for a war.

奥利瓦尔不是唯一发出此警世之言的人。微软(Microsoft)联合创始人比尔‧盖茨(Bill Gates)2018年也曾警告说,下一次大流行病可能是我们从未见过的传染病。他建议我们像应对一场战争一样,为其出现做好准备。

Meanwhile, the WHO is so firmly convinced that they have updated their list of pathogens most likely to cause a massive, deadly outbreak to include “Disease X” – a mystery microorganism which hasn’t yet entered our radar.

同时,世界卫生组织(WHO)坚信,他们已经更新了最有可能导致大规模致命疾病爆发的病原体的名单,包括“X疾病”(Disease X)在内。所谓X疾病指的是一种还没有进入我们了解范围的致命神秘微生物。

Of course, finding the deadly microbes that are still in hiding, or identifying which of the obscure or exotic pathogens that we already know about may pose a threat, is no mean feat. What can be done to hunt them down? And how can we tell which ones could really take off?

当然,要发现那些隐藏的致命微生物,或找出我们已知的奇怪病原体中哪些会对人类构成威胁,绝非易事。我们能做什么去追踪它们?我们又如何辨别哪些微生物会引发流行病?

Earlier this year, scientists from Johns Hopkins University published a report which aimed to answer these pressing questions. “Our research really arose because everybody in my field was just coming up with things that they thought were going to cause the next pandemic because they were scary, or because they had caused outbreaks – no one was trying to understand what it was about the pathogens that allowed them to have that potential,” says Amesh Adalja, who led the team. “People just kept taking lists [of potential concerns] that other people had made and adding to them, without any real rigour. Why is influenza at the top of the list? Why did we not think about Zika, before 2016? And why did we not think about West Nile in the United States?”

约翰霍普金斯大学(Johns Hopkins University)的科学家2018年曾发表一份报告,旨在回答上述紧迫的问题。团队负责人阿德加(Amesh Adalja)说:“我们之所以开始这个研究,是因为每个在此领域的科学家都提出他认为会导致下一次大流行病的病原体,或者因为这些病原体很可怕,或是它们已经引发过瘟疫,但没有人试图理解为什么这些病原体会有此可能。大家只是一直在接受他人列出的(潜在威胁)的病原体名单,然后做些添加,但不是很严谨。为什么流感要排在名单的首位?为什么2016年之前我们没有想到寨卡病毒(Zika)?为什么我们以前没有想到过西尼罗河病毒(West Nile)会在美国爆发?”

At the core of the research was the idea that pandemic pathogens are fundamentally weird. Out of millions of viruses on the planet, very few have ever caused a major outbreak. Together with his colleagues, Adalja identified the unusual combination of features that allowed them to do this.

流行病病原体习性怪异而难以捉摸,这一观点是流行病学研究的核心。地球上数以百万计的病毒中,只有极少数曾经引起了流行病大爆发。阿德加和他的同事们一起,鉴定出了让这些病毒得以肆虐的几个特征。

First of all, pandemic pathogens are almost all viruses. This is partly because of their sheer abundance and ubiquity. They are the most numerous biological entities, stalking every ecosystem and invading every type of organism. They can traverse continents and cascade down from the sky in their trillions every day; there are about 800 million viruses on every square metre of the planet.

首先,流行病原体几乎都是病毒。部分原因是病毒数量绝对的大,而且无所不在。它们是地球上数量最大的生物实体,跟随着地球上的每一个生态系统并入侵每一种生物体。它们可以穿越地球各大洲,每天有数万亿的病毒会从天而降。地球上每平方米地方的病毒多达8亿个。

When you combine their large population sizes with the lightning speed at which they can copy themselves, you end up with a pace of evolution that’s unparalleled in nature. And not only does this mean that they can outsmart our immune systems, but it’s very difficult to develop effective vaccines and anti-viral treatments. While there are several broad-spectrum antibiotics which will kill a wide variety of bacteria, there aren’t yet any equivalent drugs for viruses that actually work.

当你把它们庞大的数量和自我复制的闪电速度结合起来,你一定会得出这样的结论,病毒具有自然界无与伦比的进化速度。这不仅意味着它们可以战胜我们的免疫系统,而且人类很难开发有效的疫苗和抗病毒治疗。虽然有一些广谱抗生素可以杀死多种细菌,目前尚没有任何真正能发挥作用与抗生素等效的抗病毒药物。

One group, the RNA viruses – which have genomes made from RNA, rather than DNA – takes these characteristics to the extreme. When these super-pathogens make new copies of their genetic instructions, they don’t include a proofreading step where they check for mistakes, so mutations are common and new variants are constantly being created.

一组核糖核酸(RNA)病毒——从核糖核酸而不是脱氧核糖核酸(DNA)中提取的基因组——将病毒这些特征体现到极致。当这些超级病原体在复制自己的遗传指令时,没有检查复制是否错误的校对步骤,所以突变很常见的,因而新的病毒变异体不断被创造出来。

Many of the world’s most notorious pathogens fall into this category, including influenza, HIV, Sars, Mers, Zika, Ebola, polio and rhinovirus (the most prevalent cause of the common cold). But it also includes lesser-known threats, such as Enterovirus 68 – a rare relative of polio with a taste for babies, children and teenagers. It was only discovered in the winter of 1962, when four children were struck down with pneumonia in California.

世界上许多最臭名昭著的病原体都属于这一类,包括流感病毒、艾滋病毒(HIV)、非典病毒、中东呼吸综合征冠状病毒(Mers)、寨卡病毒、埃博拉病毒、脊髓灰质炎(polio)和鼻病毒(rhinovirus,引起普通伤风感冒的最普遍原因)。但也包括有我们很少听说的一些危险病毒,如68型肠病毒(Enterovirus 68),这是一种罕见的脊髓灰质炎相关病毒,感染者多为婴儿、儿童和青少年。该病毒只在1962年冬天被发现过,当时加利福尼亚州(California)的四个孩子因感染此病毒患肺炎死亡。

No one is suggesting that this particular virus is going to suddenly start killing millions of people, but it does satisfy all the criteria – including the final condition that it can infect the respiratory tract. “These viruses are much harder to intervene upon, because breathing is an essential part of life and it’s very hard to stop people from breathing on each other. It’s not the same thing when you’re talking about blood or body fluids,” says Adalja.

并不是说这种特别的病毒会突然造成数百万人死亡,但它的确满足所有的危险标准——包括最后的条件,即它可以感染呼吸道。阿德加说:“这些病毒更难进行干预,因为呼吸是生命必不可少的一部分,很难阻止人们呼吸。这和通过血液或体液感染不是一回事。”

After laying low in the US population, largely undetected, for several decades, Enterovirus 68 has recently been on the increase. It was linked to an outbreak of a mysterious, polio-like disorder which sprung up in the Midwest of the US in 2014 and killed four people, including a 10-year old girl. Then earlier this month, many more children in the area fell ill, experiencing a sudden paralysis of one or more limbs. So far at least 12 have tested positive for rare enteroviruses such as strain 68.

68型肠病毒在美国人口中潜伏下来后,几十年来基本上没有被发现,而最近一直发现有人感染。该病毒与一种神秘的、类似脊髓灰质炎的障碍症的发病有关,2014年在美国中西部地区爆发,造成4人死亡,其中包括一个10岁的女孩。2018年11月,美国中西部有更多孩子感染到这种病毒,症状是突然有一个或多个肢体麻痹瘫痪。到目前为止至少有12人检测出对罕见的肠道病毒如68型呈阳性反应。

According to Adalja, enteroviruses are the sort that we should be keeping an eye on. “This group has probably been grossly underestimated in terms of its pathogenicity,” he says. “There’s no enterovirus vaccine, except for polio. And there are probably enteroviruses that we haven’t discovered yet.”

阿德加认为肠道病毒是我们应该密切关注高度警惕的病毒。他说:“这个病毒族群的致病性可能被严重低估。除了脊髓灰质炎外,其他肠病毒没有预防疫苗。甚至可能还有我们还未发现的肠道病毒。”

However, perhaps the most enigmatic viruses of all are those which infect other animals. The ‘zoonotic’ pathogens include all the big names, from HIV to Nipah, having caused nearly every pandemic in human history. Just like the recent avian flu outbreak, the 1918 flu pandemic, which killed between 50 and 100 million people worldwide, began in birds.

然而,也许最神秘的病毒是那些除人类外还会感染其他动物的病毒。这些人畜互传的病原体包括艾滋病毒、尼帕病毒(Nipah)等所有曾触发人类历史上大瘟疫的恶名昭著病毒。就像最近爆发的禽流感(avian flu)和1918年的西班牙大流感,两者最初都是先在鸟类中爆发。西班牙大流感造成全球5000万至1亿人死亡。

Enter the virus hunters – scientists like Olival who travel the globe, looking for the source of the next pandemic. During the first phase of the US government’s disease surveillance program, from 2009-2014, “we found about a thousand new viruses”, he says. What is the undiscovered pool of viruses? “Oh, we estimate that it could be in the millions. There are probably millions of viruses out there that infect other mammals and could potentially infect people.” 

于是,病毒猎手,即像奥利瓦尔这样的科学家登场,他们走遍世界,寻找下一次大流行病的潜在元凶。他说,在美国政府疾病监测计划的第一阶段,从2009年到2014年,“我们发现了大约一千种新病毒”,未被发现的病毒是什么?“哦,我们估计种类可能数以百万计。可能有成百上千万的病毒感染其他哺乳动物,有的可能会传染给人。”

With such an intimidatingly large number of missing viruses in the wild, sifting the ones that will stay in other animals from the ones that could become global killers poses a significant problem. But there are some clues. For example, scientists can look out for genes that might allow a virus to latch onto human cells and sneak inside, or uncover which animals tend to carry it, since most people are much more likely to come into contact with, say, chickens than they are eagles.

大自然中还有大量的病毒未被人类发现,要从可能成为全球杀手的病毒中找到那些会传染到其他物种的病毒,是很困难的。但也有一些线索可循。例如,某类病毒的基因能够贴近并潜入人体细胞,科学家就去找带有这种基因的病毒,或找出哪些动物容易携带这种病毒并与人类很接近,比如说大多数人接触到鸡的可能性相对于接触到鹰而言,要大些。

“I think it’s one of the most exciting scientific issues right now in the field, moving from the genetic sequence of a virus to saying what is its potential infectivity of humans or other animals and what is the potential pathogenicity,” Olival says. “It’s still a bit of a holy grail, moving from the sequence to some sort of definitive answer – and every group of bugs is going to be different, in terms of which markers and genes to look at.”

奥利瓦尔说,“我认为这是此领域现在最激动人心的科学问题之一,从找出病毒的基因序列到确定病毒对人类或其他动物中的潜在传染性,以及其潜在的致病性。从基因序列到得出明确的答案,这仍然是我们追求的一个最高目标,因为每种病毒都是不同的,我们要依照其基因和基因标记来辨识。”

Back in 2017, Olival and colleagues from the EcoHealth Alliance decided to investigate where the most dangerous undiscovered pathogens are most likely to be hiding. The team examined thousands of viruses known to infect mammals, including 188 which are also known to infect humans.

2017年,奥利瓦尔和他在生态健康联盟的同事就决定调查未被发现的最危险病原体的最可能藏身之处。团队研究了成千上万已知会感染哺乳动物的病毒,包括188种也会传染给人类的病毒。

One not-so-surprising finding was that the next pandemic will probably emerge from bats. No one knows why, but bats are absolutely riddled with nasty viruses. They’re known to be the source of many, many human pandemics, including Sars, which we picked up from cave-dwelling bats in China, as well as Ebola.

一个不那么意外的发现是,下一次大流行病可能会出现于蝙蝠中。没有人知道为什么,但是蝙蝠身上绝对有很多恶意病毒。蝙蝠已知是许多人类大瘟疫的来源,包括非典和埃博拉病毒。我们已从生活在中国的窑洞里的蝙蝠身上提取到了非典病毒。

Another predictor that emerged is the range of animals they can infect – and here an obscure group of viruses called the ‘bunyaviruses’ rose to the top of the list. They have a wide variety of potential victims, from insects to plants, which means they’re likely to be able to adapt to infect humans, too. Intriguingly, the family of viruses suspected to have caused the medieval sweating disease, the hantaviruses, belong to the bunyavirus group.

另一个预报因素是病毒可以感染的动物范围。一种名不见经传的病毒群 “布尼亚病毒(bunyaviruses)”现升到了危险病毒的榜首。因为这种病毒传播对象非常广泛,其潜在的受害者从昆虫到植物,形形色色,这意味着他们也能够感染人类。有趣的是,被怀疑造成了中世纪汗热病的汉坦病毒,就属于布尼亚病毒群。

“These are viruses that most people have never heard of, but they rank quite highly in terms of their potential for pathogenicity,” says Olival.

奥利瓦尔说,“这些病毒大部分人从未听说过,但它们的潜在致病性非常高。”

Once a potential pathogen has been discovered, perhaps the greatest challenge is getting the authorities to take it seriously. According to Stephen Morse, an epidemiologist at Columbia University, this is even problematic with notorious viruses like Ebola; exotic new bunyaviruses wouldn’t stand a chance.

一旦发现一个潜在的病原体,也许最大的挑战是让政府部门能认真对待。哥伦比亚大学(Columbia University)流行病学家莫尔斯(Stephen Morse)认为,对待像埃博拉病毒这样臭名昭著的病毒甚至都存在这个问题,奇异的新布尼亚病毒就更不用说了。

“I hate to say that it could have been prevented, but the first report of the 2014 Ebola outbreak in West Africa by the WHO said, in the usual bland language, that a rapidly evolving – that should have been a red flag – outbreak of Ebola had occurred, with 43 cases. And that’s a large number,” says Morse. It was months before they mounted a response, by which time it had already made its way into cities.

莫尔斯说,“我不想说埃博拉疫情本可以避免,但世界卫生组织关于2014年西非的埃博拉疫情爆发的第一份报告用一种寻常平淡的语言说,一次快速发展的——这本该是危险信号——埃博拉疫情发生,有43例。这是一个很大的数字,”几个月后他们才作出回应,此时病毒已经传入了多个城市。

“I think we are better able to respond to pandemics today than ever, but part of the problem is mobilising the resources and political will to take them seriously,” he says. “I feel the greatest problem is not so much the pathogen – it’s complacency.”

他说,“我认为我们今天有能力更有效地应对大流行病,但部分问题是调动资源和政治意愿来认真对待它们。我觉得最大的问题并不是病原体——而是人类满足于现状。”

Finally, no list of obscure pandemic threats would be complete without a mention of smallpox. Though the virus has only been extinct in the wild since 1977, the sheer terror of the disease has largely been forgotten.

最后,在大流行病的威胁名单中如果没有提到天花就是不完整的。虽然这种病毒刚在1977年后才在自然环境中灭绝,但这种疾病的绝对恐怖在很大程度上已经被遗忘了。

Here’s a quick reminder: during its 3,000-year dominion, the smallpox virus killed hundreds of millions of people, including several European kings and queens and nearly the entire population of native North Americans. The mummified head of Egyptian pharaoh Ramesses V bears its characteristic pockmarks, as did the Soviet dictator Joseph Stalin, who required that all photographs of his face were edited to disguise them – he would reportedly have the creators of unflattering images shot.

这里有一个快速提示:在天花病毒3000年的肆虐期间,杀死人类数亿人,包括一些欧洲的国王和王后,以及几乎全部北美原住民人口。埃及法老拉美西斯五世(Ramesses V)的木乃伊头上留着痘疤,这是出过天花的特征,苏联独裁者斯大林(Joseph Stalin)也一样,他要求所有他脸部的照片都要进行编辑来掩饰那些痘疤——据报道,他会枪毙那些真实照片的拍摄者。

Smallpox has most of the ingredients you need for a major pandemic: it’s caused by a virus, and though it is unusual in having a genome made from DNA, it belongs to a family that can evolve rapidly and move easily between different animal species. Crucially, the smallpox pathogen is transmitted by breathing in droplets of particles suspended in the air. Though there haven’t been any natural infections since it was eradicated, the virus took its last victim a year after it was declared extinct, when a medical photographer contracted the disease at a lab in Birmingham in 1978. And it could happen again. To this day, smallpox stores exist at labs in Atlanta, Georgia, and in the scientific city of Koltsovo in central Russia.

天花具备主要流行病的所有元素:这是一种少见的脱氧核糖核酸病毒,通过悬浮在空气中的飞沫微粒传播,很容易在不同的动物物种中间快速传播。虽然自从宣布天花灭绝后没有出现过任何自然传染病例,但一年后天花病毒的最后一个受害者出现,一位医学摄影师于1978年在伯明翰(Birmingham)的一个实验室感染了天花。这样的事还可能再次发生。到今天,仅有的天花病毒分别存放在美国乔治亚州亚特兰大(Atlanta)和俄罗斯中部的科学城市科特索瓦(Koltsovo)两个实验室。

Back in the 1970s, most people had been vaccinated in childhood. But today state vaccination programs for the virus have been discontinued, and the only people with any immunity are middle aged or older. The United States and many other countries have stockpiles of the vaccine, just in case. Even so, an outbreak of such a contagious disease could easily rip across the globe and kill millions.

回到20世纪70年代,那时大多数人在童年时期都接种过天花疫苗。但今天所有国家的天花病毒疫苗接种项目已经终止,唯一有免疫力的人口都已到中年,或年龄更大。以防万一,美国和其他许多国家还有疫苗储备。即便如此,诸如此类的接触性传染病的爆发很容易在全球蔓延,杀死数百万人。

Then there’s the risk of bioterrorism. It’s now possible to build viruses from scratch, using nothing more than their genetic sequence for instructions, so you don’t need to be a government scientist to have access to the world’s most lethal pathogen. If it’s ever released, the virus could change the world forever. As Bill Gates put it last year “With nuclear weapons, you’d think you would probably stop after killing 100 million. Smallpox won’t stop. Because the population is naïve, and there are no real preparations. That, if it got out and spread, would be a larger number.”

还有生物恐怖主义的风险。现在只需要使用基因序列指令,就可以从零开始构建病毒,所以你不需要成为政府科学家也能接触到世界上最致命的病原体。病毒一旦被释放出来,将会永远改变世界。正如比尔‧盖茨去年所说 “拥有核武器,你认为你可能会杀掉1亿人以后停下来。而天花不会停止。因为人类是天真的,并没有真正做好准备。如果它被释放并传播,死亡人数将会更多。”

It may have been centuries since the dreaded sweating sickness of 1485, but we can still learn from the past. The flu is seen as a likely candidate for the next pandemic – not the only candidate. And if the scientists have got it right, failing to take D-list viruses seriously could be a catastrophic mistake.

距离1485年那场可怕的汗热病已过了几个世纪,但我们仍然可以从这一瘟疫吸取教训。流感病毒被认为可能是造成下一次瘟疫大爆发的候选凶手——但流感病毒不会是唯一的候选者。如果科学家们是对的,未能认真对待那些致命病毒可能是灾难性的错误。
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