I am so at home in Dublin, more than any other city, that I feel it has always been familiar to me. It took me years to see through its soft charm to its bitter prickly kernel - which I quite like too.

Home Uncategorized A Postmodern Disease

A Postmodern Disease

Seamus O’Mahony

The Gluten Lie: And other myths about what you eat, by Alan Levinovitz, Regan Arts, 263 pp, $24.95, ISBN: 978-19413930602

Gluten Attack: Is gluten waging war on our health?,  by Professor David Sanders, Vermilion, 200 pp, £12.99, ISBN: 978-1785040160

Willem-Karel Dicke (1905-1962) was a paediatrician who practised at the Juliana Children’s Hospital in The Hague, and later (after World War II) at the Wilhelmina Children’s Hospital in Utrecht. He looked after many children with coeliac disease, also called Gee-Herter’s disease. This was a mysterious condition which caused malabsorption of nutrients in food, leading to diarrhoea, weight loss, abdominal distension, anaemia and growth failure. Many had bone deformity due to rickets (caused by lack of vitamin D), and death was not uncommon: a 1939 paper from Great Ormond Street Hospital reported a mortality rate of 30 per cent among coeliac children. The great Australian paediatrician Charlotte Anderson wrote that she saw these children “languish in hospital for months, miserable and depressed”.

It had long been suspected that the disease was food-related, and various diets, such as Haas’s banana diet, were tried, but none was consistently effective. During the 1930s, Dicke heard of several anecdotal cases of coeliac children who improved when wheat was excluded from their diet. Towards the end of World War II, during the winter of 1944-45 – the hongerwinter, or “winter of starvation” – Holland experienced a severe shortage of many foods, including bread, and the Dutch were famously reduced to eating tulip bulbs. Dicke noticed that his coeliac children appeared to be getting better when their “gruel” was made from rice or potato flour instead of the usual wheat. Dicke attended the International Congress of Paediatrics in New York in 1947, and, although he was a modest and reticent man, he told as many of his colleagues as he could about his observation on wheat and coeliac disease. Years later, Dicke’s colleague and collaborator, the biochemist Jan van de Kamer wrote: “However, nobody believed him and he came back from the States very disappointed but unshocked in his opinion.”

Dicke moved to Utrecht, and formed a research partnership with van de Kamer, who had developed a method for measuring the fat content of faeces. This was a means of quantifying the malabsorption of food from the intestine in these children. He began a series of clinical trials of wheat exclusion, and showed that coeliac children got better on this diet. By measuring faecal fat content before and after wheat exclusion, he demonstrated objective evidence of the benefit of this diet. Later, he showed that gluten (the protein which gives bread its elastic quality) was the component in wheat responsible for the disease. Dicke wrote a paper describing his findings and sent it to one of the main American paediatric journals. He did not receive an acknowledgement, and the manuscript wasn’t even sent out for review. Meanwhile, a research group at Birmingham University and the Birmingham Children’s Hospital had heard of Dicke’s work and wanted to confirm his findings. Dicke was a gracious and generous man who did not regard this group as competitors, and he actively assisted them. One of that group, Charlotte Anderson, visited Dicke to see his studies of coeliac children first hand. Dicke went out his way to help Anderson with her research; she later paid tribute to “his old-world gentility”.

Dicke had formally written up his findings for his doctoral thesis, presented to the University of Utrecht in 1950. He also sent off a paper to the Swedish journal Acta Paediatrica Scandanavica. By the time that paper was eventually published in 1953, the Birmingham group had already reported their results in the Lancet. Dicke died young, at fifty-seven, after a series of strokes.

When I qualified as a doctor in 1983, coeliac disease was a well-recognised, although relatively uncommon condition, affecting about one in every two thousand people in Britain. It was then much more prevalent in Ireland, particularly in Co Galway, where the disease was diagnosed in one in every three hundred of the population. In retrospect, this was at least partly due to the fact that the professors of medicine and paediatrics at University College Galway at that time both had a special interest in the condition and actively sought it out. Making a formal diagnosis of coeliac disease in the early 1980s was difficult: a biopsy had to be taken from the upper small intestine – the jejunum – and this was carried out using an instrument known as a Crosby capsule. Obtaining a biopsy with this capsule was technically difficult, time-consuming and very uncomfortable for the patient. Gradually, the diagnosis became easier. By the late 1980s, biopsies could be obtained using an endoscope, in a procedure that took five to ten minutes. In the 1990s, blood antibody tests became widely available, and were shown to be highly accurate. The ease of these testing methods, along with greater awareness of the condition, led to a steep rise in diagnosis of coeliac disease during the 1990s and 2000s: about one per cent of the British and Irish population are now thought to have coeliac disease, although most remain undiagnosed. Coeliac disease is no longer regarded as primarily a disease of children: the diagnosis can be made at any age. Several screening studies across Europe and the US, using antibody tests, show that the prevalence of coeliac disease is now somewhere between 1and 2 per cent of the population. The treatment – a gluten-free diet – is lifelong and effective.

The patients I diagnosed with coeliac disease in the 1980s were often quite ill; nowadays, most adults diagnosed with coeliac disease have minimal or no symptoms. Many have typical features of irritable bowel syndrome (IBS), such as bloating and abdominal discomfort; others are diagnosed because they have a family history. The ease of diagnosis and increased public awareness of the condition led many people with various chronic undiagnosed ailments to seek tests for coeliac disease. These “medically unexplained” conditions include IBS, chronic fatigue, and fibromyalgia. Some did indeed have coeliac disease, but most didn’t. Undaunted by negative tests for coeliac disease, some people with these symptoms tried a gluten-free diet, and found that they felt better. Their doctors put this down to suggestibility and the placebo effect. Many complementary and alternative medicine practitioners, however, thought it was a real phenomenon, and began to recommend a gluten-free diet for all sort of chronic ailments.

In 1980, a Birmingham-based gastroenterologist called Brian Cooper wrote a paper for the prestigious American medical journal Gastroenterology, in which he described eight women with chronic diarrhoea who responded to a gluten-free diet, even though they didn’t have coeliac disease. This study was small – almost anecdotal – without a control group, and the observed response to gluten-free diet might have been coincidental. The paper made little impression at the time, but the concept of “Non-Coeliac Gluten Sensitivity” re-emerged in about 2010, and many cited Cooper’s paper as the first description of this syndrome. Doctors were now seeing many patients who were convinced that they were gluten sensitive, despite testing negative for coeliac disease. These patients were not satisfied with reassurances along the lines of “well, you’re not coeliac, but if it makes you feel better give the diet a go” and demanded a formal diagnostic label for what ailed them. As the bitter history of Chronic Fatigue Syndrome/ME has shown, patients with “medically unexplained” symptoms are often resistant to psychological explanations. Our contemporary culture, for all its superficial familiarity with psychology and its vocabulary, is very uncomfortable with the notion of “psychosomatic” disease. Many of my IBS patients prefer gluten sensitivity as an explanation for their symptoms, and some people with chronic fatigue believe they have infection with the bacterium that causes Lyme disease. Doctors now spend much of their time manoeuvring the ever-widening gap between their patients’ beliefs and their own.

By 2010, coeliac disease researchers had run out of new ideas. Then came “Non-Coeliac Gluten Sensitivity”, which they seized on as a golden opportunity to expand their academic territory. In February 2011, fifteen of them met at a hotel near Heathrow airport. They were keen to give this phenomenon of self-diagnosed gluten sensitivity some form of medical credibility, or, as they put it, to “develop a consensus on new nomenclature and classification of gluten-related disorders”. They were not shy about the commercial agenda:

Now we are observing another interesting phenomenon that is generating great confusion among health professionals. The number of individuals embracing a gluten-free diet appears much higher than the projected number of celiac disease patients, fuelling a global market of gluten-free products approaching $2.5 billion in global sales in 2010. This trend is supported by the notion that, along with celiac disease, other conditions related to the ingestion of gluten have emerged as health care concerns.

This meeting was sponsored by Dr Schär, a leading manufacturer of gluten-free foods. A summary of this meeting was published in the journal BMC Medicine in 2012; Dr Schär paid for the “article-processing charge”. “Gluten sensitivity” now became a recognised part of “the spectrum of gluten-related disorders”. The paper concluded with some speculation “as to why this dietary protein is toxic for so many individuals in the world”:

One possible explanation is that the selection of wheat varieties with higher gluten content has been a continuous process during the last 10,000 years, with changes dictated more by technological rather than nutritional reasons. Wheat varieties grown for thousands of years and most used for human nutrition during the Middle Ages … contain less quantities of the highly toxic 33-mer gluten peptide. Apparently the human organism is still largely vulnerable to the toxic effects of this protein complex, particularly due to a lack of adequate adaptation of the gastrointestinal and immunological responses.
Additionally, gluten is one of the most abundant and diffusely spread dietary components for most populations, particularly those of European origin. In Europe, the mean consumption of gluten is 10 g to 20 g per day, with segments of the general population consuming as much as 50 g of daily gluten or more. All individuals (my italics), even those with a low degree of risk, are therefore susceptible to some form of gluten reaction during their life span.

Dr Schär must have been pleased with this consensus, which led to several studies on gluten sensitivity over the next few years. In these trials, patients with self-diagnosed gluten sensitivity were randomly allocated to a challenge with gluten (disguised in a capsule) or to an inert, harmless placebo, and the response to these challenges was measured by symptom scores. This is called “Double-Blind Placebo-Controlled Oral Challenge”. It is difficult to assess the literature objectively, as many of these studies were poorly designed, badly written up, and published in low-impact journals. To add to the confusion, some patients recruited into these trials undoubtedly had a subtle, low-grade form of true coeliac disease (“coeliac lite”), and should have been excluded.

A respected research group based at Monash University in Melbourne published a paper in the American Journal of Gastroenterology in 2011, which reported that IBS patients did indeed appear to react when exposed to gluten. In 2012, an Italian group published a paper in the same highly-regarded journal, which reported similar findings, but with wheat, and not specifically gluten. (Wheat contains several other proteins, sugars and starches.) The Australian group had previously shown that many IBS patients were intolerant to a group of food components called “FODMAPs”. FODMAPs – an acronym for fermentable oligosaccharides, disaccharides, monosaccharides and polyols – are a diverse group of sugars and starches found in fruits (apples, pears), cereals (wheat, rye), dairy produce and vegetables (onions, beans). These FODMAPs are osmotic, pulling water into the intestine, and are fermented by bacteria in the colon, producing gas which causes bloating and farting. They decided to look again at patients with IBS and self-diagnosed gluten sensitivity, and did a further study, which they published in Gastroenterology in 2014. This time, to control for other potential triggers of gut symptoms, they placed the patients on a low FODMAP diet before challenge with gluten or placebo. They found that the patients responded to a low FODMAP diet, but gluten alone had no effect. They measured markers of intestinal inflammation in blood and faeces, and found no change after challenge with gluten. They concluded that these IBS patients were reacting to FODMAPs, not gluten. Intriguingly, most of these patients opted to continue on a gluten-free diet, even when they were told that they were not gluten sensitive.

Despite these inconclusive studies, many review articles appeared in the medical journals describing the symptoms of gluten sensitivity and how to diagnose it. Many of these papers appeared in the journal Nutrients. Professor Carlo Catassi, an Italian paediatrician, has published several papers on gluten sensitivity, mainly in Nutrients. He is probably the most prominent name associated with gluten sensitivity, and has received “consultancy funding” from the Dr Schär Institute. In a 2015 review article for the Annals of Nutrition & Metabolism, Catassi listed the following as clinical manifestations of gluten sensitivity: bloating, abdominal pain, lack of wellbeing, tiredness, diarrhoea, nausea, aerophagia (swallowing air), gastro-oesophageal reflux, mouth ulcers, constipation, headache, anxiety, “foggy mind”, numbness, joint and muscle pain, skin rash, weight loss, anaemia, loss of balance, depression, rhinitis, asthma, weight gain, cystitis, irregular periods, “sensory” symptoms, disturbed sleep pattern, hallucinations, mood swings, autism, schizophrenia, and finally (my favourite) “ingrown hairs”. “Non-Coeliac Gluten Sensitivity”, Catassi concludes, “is a recently ‘rediscovered’ planet in the astronomical system of gluten-related disorders.” In a Disclosure Statement, we are told that “the writing of this article was supported by Nestlé Nutrition Institute”.

Professor Catassi is the first author, too, of a paper entitled “Diagnosis of Non-Coeliac Gluten Sensitivity (NCGS): The Salerno Experts’ Criteria”, published in Nutrients. In October 2014, a group of thirty “International experts” met in Salerno, Italy, “to reach a consensus on how the diagnosis of Non-Coeliac Gluten Sensitivity should be confirmed”. The meeting was again funded by Dr Schär. Only six of the fifteen experts who met at Heathrow made it to Salerno; was there an early schism in the church of gluten sensitivity? The Salerno experts decided that diagnosis of gluten sensitivity required a “Two-Step” approach. In step one, patients suspected of having gluten sensitivity are put on a gluten-free diet for six weeks. They are assessed every week by a symptom score; a symptomatic response is defined as “a decrease of at least thirty per cent of the baseline score … for at least 50 per cent of the observation time”. Those who passed these (decidedly arbitrary) criteria, then progressed to stage two. Stage two is a “Double-Blind Placebo-Controlled Challenge with Crossover”. In other words, the patients are randomised to being exposed to either disguised gluten or placebo, and their response was assessed by symptom questionnaire. Again the figure of thirty per cent was chosen as the threshold variation between the gluten and the placebo challenge to discriminate a positive from a negative result. The experts concede that “The threshold of 30 per cent increment in symptoms is somewhat arbitrary and needs scientific validation.” Whatever about this arbitrary figure, the most important feature of this “Two-Step” diagnosis is that it is completely impractical in clinical practice, effectively consigning it to formal research trials only. Paradoxically, this strengthens the case for gluten sensitivity: if doctors can’t routinely diagnose the condition, they will simply have to accept the patient’s self-diagnosis of gluten sensitivity at face value and recommend a gluten-free diet.

The only conclusion that can be made from the studies to date is that we don’t know whether gluten sensitivity even exists. The appropriate, cautious, scientific response to these data should have been a suspension of judgement. Professor Peter Gibson, the leader of the Monash University researchers, explained, somewhat wearily, in an interview: “People said the researchers in Australia have changed their minds. They don’t understand what science is. We didn’t change our minds. We just produced more data … nothing has been proved.” The question can only be resolved by further studies, with strict, agreed common protocols and recruitment criteria. The experts, however, instead of waiting until more data became available, gave us the Salerno Criteria on how to diagnose a condition that may not exist. Gluten sensitivity is thus a model for what might be called a postmodern disease. It’s “discovery” owes much to patient pressure and the suborning of expert opinion by commercial interests. It does not have a validated biological marker (such as a blood test or a biopsy), and the diagnosis is made by a dubious and highly arbitrary symptom score.

I found a picture online of the experts gathered at Salerno, and was reminded of a fresco in the Sistine chapel depicting the first Council of Nicea in 325 AD. The council was convened by the emperor Constantine to establish doctrinal orthodoxy within the early Christian Church. The industry-sponsored get-together in Salerno had similar aims. Why did these experts attach their names to a consensus on how to diagnose this postmodern pseudo-disease? Unlike Willem-Karel Dicke, who was a clinical doctor who happened to stumble on an idea that he desperately wanted to test, modern medical researchers are an intensely competitive professional academic caste. They market “their” diseases (and thus, their research) as aggressively as any commercial enterprise, and the line that used to separate the university and commerce has become decidedly blurred. In 2000, Dr Marcia Angell wrote an editorial in the New England Journal of Medicine (America’s most prestigious medical journal) entitled “Is Academic Medicine for Sale?” in which she warned against the increasingly unhealthy relationship between medical researchers and industry, particularly Big Pharma. Shortly after, a Dr Thomas J Ruane wrote to the journal: “Is academic medicine for sale? No, the current owners are very happy with it.”

Few of these contemporary experts share Dicke’s qualities of modesty, reticence and “old-world gentility”. It is very much in their interest to “expand the astronomical system of gluten-related disorders” and to “raise awareness”. David Sanders, professor of gastroenterology at the Royal Hallamshire Hospital in Sheffield (present both at Heathrow and Salerno), has written a book for a general readership called Gluten Attack: Is gluten waging war on our health? Despite putting his name to the Salerno Criteria, in this book he is decidedly lukewarm and non-committal about gluten sensitivity: “there is much to be said on both sides of the debate. Whether you think it is gluten or FODMAPs and let’s not forget wheat! So if the doctors are confused what can the poor patient do!” He is relaxed about industry-sponsored research: “Many would suggest that this is a conflict of interest. The problem is this: what do you do if you cannot get funding for your idea? Then you are very grateful if you find a commercial sponsor.”

Although the coeliac disease experts accepted commercial sponsorship and then obligingly legitimised the highly dubious entity that is gluten sensitivity, two entrepreneurial American doctors, William Davis, author of Wheat Belly (2011), and David Perlmutter, author of Grain Brain (2013), took the hysteria to the next level. Their best-selling books contributed substantially to the popular perception of gluten as toxic not just for coeliacs but for everyone. Neither Davis (a cardiologist) nor Perlmutter (a neurologist) had any expertise or research track-record in coeliac disease or gluten sensitivity, but the fact that both used “MD” after their names gave their best-selling books a bogus scientific credibility. Davis argues that “modern” wheat is a “perfect, chronic poison”, is addictive and is the main cause of the current obesity epidemic. Perlmutter claims that “modern grains are destroying your brain”, causing not only Alzheimer’s disease, but also “‘chronic headaches, depression, epilepsy, and extreme moodiness”. This list is, of course, absurd, and completely unsupported by any evidence, but it is a model of restraint compared to Professor Catassi’s list of “clinical manifestations of gluten sensitivity”. Perlmutter’s and Davis’s books have sold in their hundreds of thousands, but are dismissed by scientists. Science, however, should be more concerned about the reputational damage inflicted on it by the feverish musings of the Salerno/Heathrow experts.

Twenty million Americans claim that they experience symptoms after eating gluten. One-third of adults in the US say they are reducing or eliminating their gluten intake. You can buy gluten-free shampoo, and even go on a gluten-free holiday. It is easy to mock this foolishness, and many do: look up JP Sears’s “How to become gluten intolerant” on YouTube. A US marketing firm called Cataline has estimated that the average gluten-free grocery basket costs $100 compared to $33 for the average basket. Even the gluten sensitivity evangelists are getting a bit alarmed by this social phenomenon. Alessio Fasano, an Italian paediatric gastroenterologist who works at the Mass General Hospital for Children in Boston, and one of only six coeliac disease experts who attended both the Heathrow and Salerno meetings, told the BBC reporter William Kremer: “We started this crusade, so to speak, to really make the North American community aware that coeliac disease existed. We didn’t realise that this pendulum was going out of control and go all the way to the other side.” Fasano, like David Sanders, has also published his own book, Gluten Freedom, because he was “frustrated by sensationalist coverage”.

Meanwhile, several celebrities, including Gwyneth Paltrow, Miley Cyrus and Novak Djokovic, have proclaimed the benefits of gluten exclusion for one’s general health. “Everyone should try no gluten for a week!” tweeted Miley Cyrus, “The change in your skin, physical and mental health is amazing! U won’t go back!” Up to fifty per cent of elite athletes are thought to be on a gluten-free diet. Popular magazines ran stories on how a gluten-free diet helped weight loss, and many new diets, such as the “paleo” diet, are effectively gluten-free. The gluten-free food market, which had hitherto been a small, niche business, has expanded rapidly over the last several years. In 2014, sales of gluten-free foods in the US totalled $12.18 billion; it has been estimated that this market will grow to $23.9 billion by 2020.

YouGov, the internet-based market research firm, recently produced a report called “Understanding the FreeFrom consumer”. Gluten-free is not the only “FreeFrom” food: consumers can choose lactose-free, dairy-free, nut-free, soya-free, and many other products. Marketing experts also predict a rapid growth in FODMAP-free food sales. Nearly one in five of the UK population consider themselves to have a food allergy or intolerance; a quarter of UK households include at least one allergy or intolerance sufferer. Three-quarters of these food sensitivities are self-diagnosed. Ten per cent of the UK population are “cutting down” on gluten. Remarkably, two-thirds of those cutting down gluten do not have a sensitivity, self-diagnosed or otherwise, and are referred to as “lifestylers” by the marketing experts. These gluten-excluders tend to be younger, of higher social class, and female. They are more likely to be vegetarians, regular exercisers, and “spiritual but not religious”. The main reason given for cutting down on gluten is that is “generally healthier”. Specific perceived benefits include weight loss and improved energy. The “free-from” food market is booming, with annual sales of £740 million; gluten-free making up fifty-nine per cent of it. This market is growing at a rate of roughly thirty per cent annually.

Fred Brouns, professor of Health Food Innovation Management at Maastricht University, wrote the pithily entitled review “Does wheat make us fat and sick?” for the Journal of Cereal Science in 2013. He examined the claims made against wheat by both William Davis and David Perlmutter, namely, that it causes weight gain, makes us diabetic, and is addictive. He addressed also the charge (made by Davis, Perlmutter and the Heathrow experts that modern wheat contains higher levels of toxic proteins. Brouns and his colleagues reviewed all the available scientific literature on wheat biochemistry, and concluded that wheat (particularly whole wheat), has significant health benefits, including reduced rates of type 2 diabetes and heart disease. He found no evidence that the wheat we eat now is in any way different from that consumed during the Palaeolithic era, apart from having higher yields and being more resistant to pests. Genetically modified wheat has not been marketed or grown commercially in any country. “There is no evidence,” he concluded, “that selective breeding has resulted in detrimental effects on the nutritional properties or health benefits of the wheat grain.”

America leads the way in the demonisation of gluten. I am amused by this, because up to recently, US doctors ignored coeliac disease, and the overwhelming majority of research papers came from Europe. As recently as 1993, a review article in the New England Journal of Medicine on evaluation of iron-deficiency anaemia did not once mention coeliac disease, a common cause of this condition. Now that Americans are obsessed with gluten, many grand US teaching hospitals have “Celiac Disease Centers”. Alan Levinovitz, a professor of religion at James Madison University in Virginia, was struck by the parallels between contemporary American fears about gluten and the story of the “grain-free” monks of ancient China. These early Daoists, who flourished two thousand years ago, believed that “the five grains” (which included millet, hemp and rice) were “the scissors that cut off life”, and led to disease and death. They believed that a diet free of the five grains led to perfect health, immortality, and even the ability to fly. In his book The Gluten Lie Levinovitz places contemporary American anxieties about gluten in a long line of food-related myths:

As with MSG, the public’s expectation of harm from gluten is fuelled by highly profitable, unscientific fearmongering, validated by credentialed doctors. These doctors tap into deep-rooted worries about modernity and technology, identify a single cause of all our problems, and offer an easy solution.

Does it really matter if many people adhere to a gluten-free diet unnecessarily? After all, it’s their own choice, and if they’re happy with it, why should we bread-eaters fret? The gluten story is a symptom of the growing gap between rich and poor. For most of human history, the main anxiety about food was the lack of it. Now, the wealthy worried regard food as full of threats to their health and are willing to pay a premium for “free-from” products. The notion that food has to be processed to render it safe creates a climate which will inevitably contribute to rising food costs. People who do not have scientific knowledge are likely to take the food industry’s claims at face value, and start to buy these “free-from” foods. Their children, bombarded with advertising on social media and television, will add to the pressure. What if Johnny’s poor school performance and lack of concentration is caused by gluten? What if Mary’s snuffly nose is due to lactose intolerance? When food was scarce, fussiness about it was frowned upon and socially stigmatised because it was wasteful of a precious resource. What used to be simple fussiness has now progressed to self-righteous grand-standing: people with self-diagnosed food allergies and intolerances often use this diagnosis to control others. More worryingly, self-imposed exclusion diets are often the first step on the via dolorosa of chronic eating disorders.

We have a strange paradox: the majority of people who should be on a gluten-free diet (those with coeliac disease) aren’t, because most people with coeliac disease remain undiagnosed. The majority of those who are on a gluten-free diet shouldn’t be, because they do not have coeliac disease. The “lifestylers” are deluded, and we don’t know if NCGS is a real entity (it almost certainly isn’t). People with coeliac disease are ambivalent about the gluten-free fad: they have benefited, because gluten-free produce is now easily obtained and restaurants and supermarkets are very “gluten aware”. They resent, however, the narcissistic lifestylers and self-diagnosed gluten intolerant for trivialising the condition of the one per cent who really do need to go gluten-free. Willem-Karel Dicke’s inspiration during the hongerwinter saved the lives of many sick children. I wonder what this humble, old-fashioned doctor would have made of Miley Cyrus, the Salerno Experts and Drs Perlmutter and Davis.

1/2/2017


 Seamus O’Mahony is a consultant physician and a regular contributor to the Dublin Review of Books. His book The Way We Die Now is published this week by Head of Zeus.

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