Saturday, 31 March 2018

Recipes Project - Thinking About 17th c. Potatoes (And Eating Them)

Amanda Herbert, Early Modern, Food and Drink 24/01/2017 Amanda Herbert Amanda E. Herbert [A version of this post appeared on the Folger’s Shakespeare & Beyond blog, a current, sometimes playful, and always lively resource on a wide range of Shakespeare topics. Shakespeare & Beyond is created for the great variety of Shakespeare enthusiasts—young and old, from across the US and around the world. You can see the original post here, and read more about our “recreation” of the recipe in a related post, here.] Potatoes are an iconic food in the United States They’re a staple of most American diets, and at holiday meals they often appear twice – white potatoes mashed with butter, and sweet potatoes layered into casseroles with gooey marshmallows melted on top (a dish invented by the Cracker Jack Company in 1917) – on tables around the country. But potatoes have a complex and sometimes troubled American history, one that started outside of today’s United States. Culinary historians and archaeobotanists now think that potatoes originated in Peru, and they were eaten by women and men living in South and Central America long before western Europeans arrived in these areas in the fifteenth century. Sweet potatoes (Ipomoea batatas) are frequently conflated or confused with yams (genus Dioscorea), and this slippage began in the fifteenth and sixteenth centuries. Sweet potatoes are of American origin, but their first major migration was westward, across the Pacific: in the 13th c. CE, they were taken to Easter Island and Hawaii, and later to New Zealand. At the end of the fifteenth century, they traveled eastward across the Atlantic, when they were brought back to Spain by Christopher Columbus around 1493. Yams, another edible root crop, are native to many different places around the world: Africa (Dioscorea cayenensis), Southeast Asia (Dioscorea alata, batatus, bulbifera, esculenta, japonica, and opposita) and even South America (Dioscorea trifida). Potatoes and yams have a high yield, thrive in any kind of soil, are drought-resistant, and grow in many different climatic zones. Their taste is not dissimilar and neither is their method of cultivation (although yams extend much deeper underground and it takes more work to dig them up). And in the fifteenth and sixteenth centuries, people of African, American, Asian, and European origin were all growing, selling, and eating these plants, and they didn’t always do a good job of distinguishing between them. By 1500, the sweet potato (and/or yams) had become an established crop in western Europe. They were a staple of European sailors’ diets. And they were fed – often with great violence, and by force – to enslaved women and men, on the African continent, during the middle passage, and after arrival in the Caribbean and the Americas. “Common,” or white potatoes, took a bit longer to catch on; they arrived in Europe as a cultivable vegetable between 1550-1570. Metropolitan Britain was one of the last European countries to take to the potato; the first mention of potatoes (sweet, “common,” or otherwise) in a printed British book was in 1596, when famed herbalist and botanist John Gerard included it in his Catalogue. This was apparently so well-received that a year later, Gerard devoted an entire chapter of his famous 1597 Herbal to this new and unfamiliar plant. "Of Potatoes of Virginia," in John Gerard, The Herball (London, 1597). Image courtesy of the Folger Shakespeare Library. “Of Potatoes of Virginia,” in John Gerard, The Herball (London, 1597). Image courtesy of the Folger Shakespeare Library. Over the course of the seventeenth century, more and more British subjects – enslaved and free, and on both sides of the Atlantic – began to grow, harvest, cook, and eat potatoes (as well as, and alongside, yams). In the early modern period, news of the potato spread through contact with print as well as people. Women and men learned about potatoes through experimentation, books, and word-of-mouth. They exchanged potato recipes with friends. They shared potato cuttings with their neighbors. They read about potatoes and tried their hands at preparing them. And some were forced to learn about and eat potatoes out of necessity, because they had – or were given – nothing else. A team of Folger researchers recently uncovered a very early European potato recipe in our archives. The Folger Library in Washington, DC is proud home to the largest collection of early modern western European recipe books in the United States. And in one of these recipe books, a manuscript collection kept by the Grenville family from c. 1640-1750, is a recipe entitled “to make a potato puding.” The recipe called for some ingredients that would have been familiar to any early modern British person, like butter and eggs. But it also included ingredients that might have seemed luxurious and even exotic: sweet wine imported from Spain, cinnamon (which was sourced from India and Sri Lanka in the early modern period), and three pounds of potatoes. This recipe reveals one family’s attempt to bring a new and unfamiliar food to their table, but it also teaches us about wealth and social status in seventeenth-century Britain. The Grenville’s potato pudding was a fancy dish, saved for special occasions, and something that most early modern families would not have been able to afford. Cookery and medicinal recipes of the Granville family, (ca. 1640-ca. 1750), V.a.430, Folger Shakespeare Library. Image courtesy of the Folger Shakespeare Library. Cookery and medicinal recipes of the Granville family, (ca. 1640-ca. 1750), V.a.430, Folger Shakespeare Library. Image courtesy of the Folger Shakespeare Library. We learned a lot about early modern markets, economies, foodways, and methods of cultivation as we studied the Grenville recipe for potato pudding, but we also wanted to try it for ourselves. So we invited Dr. Amanda Moniz, a former professional chef, veteran Recipes Project contributor, and the Smithsonian National Museum of American History’s new David M. Rubenstein Curator of Philanthropy, to visit the Folger in order to help us re-create the Grenville’s potato pudding in our test-kitchen. We faced three major challenges in making this dish in a form that early modern people would have recognized. First, the recipe calls for sack, a type of sweet fortified wine originally produced in Spain and the Canary Islands. Sack fell out of use in the nineteenth century, and isn’t available in most American markets. The closest approximation to early modern sack is modern sherry, and especially a dark sherry like Oloroso, which is what we used in our adaptation. The second challenge is that the pudding calls for a lot of eggs: eight of them, both whites and yolks. Early modern eggs were smaller, less uniform, and had different moisture levels than our modern American ones. In order to reach the right consistency, we cut the number of eggs in our potato pudding down to five, and we adjusted our cooking time from 30 minutes to 45 minutes so that the pudding would set properly. And last, the recipe doesn’t specify what types of potatoes the Grenvilles used in their pudding. But since sweet potatoes were the first kind of potato to be widely adopted in early modern Europe – and since we thought that those flavors would be more familiar to most modern Americans today – that’s what we chose. When it was finished, the potato pudding was delicious, earning high marks from all of the members of our Folger tasting team. Creamy and rich, delicately scented with sweet wine and cinnamon, this early modern sweet potato pudding was both unusual and familiar, imparting a sense of the past without compromising the sensibilities of a present-day palate. We don’t know how often the Grenvilles made this potato pudding, but I’m going to be making it again very soon. Sweet potato pudding. Image courtesy of the author. Sweet potato pudding. Image courtesy of the author. The Grenville Family’s Sweet Potato Pudding (adaptation) Ingredients: 3 lbs. sweet potatoes, peeled and cut into 2-inch pieces ¾ lb. butter, softened ½ c. sherry (we recommend a dark sherry like Oloroso) ½ tsp. ground cinnamon 5 whole eggs, lightly beaten Directions: Preheat your oven to 350F. Bring a large pot of unsalted water to a boil. Add potato pieces and cook until tender. Drain. In a large bowl, mash the potatoes with the butter until uniform and combined. Fold in the sherry, cinnamon, and eggs. Bake in a buttered casserole dish for 45 minutes, or until the pudding has pulled away from the sides of the dish and the middle jiggles slightly when shaken gently. The pudding will continue to set as it cools. Sources & References: Laura Mason and Catherine Brown, The Taste of Britain (London: Harper Press, 2006); Jancis Robinson, The Oxford Companion to Wine, 3rd ed. (Oxford: Oxford University Press, 2006); L.A. Clarkson and E. Margaret Crawford, Feast and Famine: Food and Nutrition in Ireland 1500-1920 (Oxford UK: Oxford University Press, 2001); Alan Davidson, The Oxford Companion to Food (Oxford UK: Oxford University Press, 1999); Sara Paston-Williams, The Art of Dining: A History of Cooking and Eating (London: National Trust Enterprises Ltd., 1993); Alfred Crosby, The Columbian Exchange: Biological and Cultural Consequences of 1492 (Westport CT: Greenwood Publishing, 1972); Redcliffe N. Salaman, The History and Social Influence of the Potato (Cambridge UK: Cambridge University Press, 1949). Interested in learning more about early modern potatoes? Check out this Recipes Project post by Rebecca Earle from 2014, and learn more about her ongoing research project “The Early Modern Potato: A Global History.”

Hepatoprotective Activity of Easter Lily (Lilium longiflorum Thunb.) Bulb Extracts.

Format: Abstract Send to J Agric Food Chem. 2015 Nov 11;63(44):9722-8. doi: 10.1021/acs.jafc.5b04078. Epub 2015 Oct 30. Tang W1, Munafo JP Jr2, Palatini K3,4, Esposito D3,4, Huang MT5, Komarnytsky S3,4, Ho CT1, Gianfagna TJ2. Author information 1 Department of Food Science, Rutgers-The State University of New Jersey , 65 Dudley Road, New Brunswick, New Jersey 08901, United States. 2 Department of Plant Biology, Rutgers-The State University of New Jersey , 59 Dudley Road, New Brunswick, New Jersey 08901, United States. 3 Plants for Human Health Institute, North Carolina State University, North Carolina Research Campus , 600 Laureate Way, Kannapolis, North Carolina 28081, United States. 4 Department of Food, Bioprocessing & Nutrition Sciences, North Carolina State University , 400 Dan Allen Drive, Raleigh, North Carolina 27695, United States. 5 Department of Chemical Biology, Rutgers-The State University of New Jersey , 160 Frelinghuysen Road, Piscataway, New Jersey 08854, United States. Abstract The hepatoprotective activities of two different extracts, a hydroethanolic crude bulb extract (CB) and a steroidal glycoside-rich 1-butanol extract (BuOH), prepared from the bulbs of Easter lily (Lilium longiflorum Thunb.), were evaluated in a 24 week study in the female KK.Cg-A(y)/J Type 2 diabetic mouse model. Animals were divided into six groups (n = 16): control mice received Easter lily bulb extract-free drinking water together with a low- or high-fat diet (diabetic control); drinking water for the remaining groups was supplemented with CB extract (1%), BuOH extract (0.1 or 0.2%), and reference drug Metformin (0.001%), together with a high-fat diet. Both CB and BuOH extract treatment groups exhibited significantly improved liver function based on comparisons of triglycerides [diabetic 219 ± 34 mg/dL, CB 131 ± 27 mg/dL, BuOH(0.2%) 114 ± 35 mg/dL], CB total cholesterol (TC) (diabetic 196 ± 12 mg/dL, CB 159 ± 5 mg/dL), average liver mass [diabetic 2.96 ± 0.13 g, CB 2.58 ± 0.08 g, BuOH(0.1%) 2.48 ± 0.13 g], alanine transferase [diabetic 74 ± 5 units/L, CB 25 ± 1 units/L, BuOH(0.1%) 45 ± 1 units/L], and histological examinations. Glucose metabolism was improved only in CB, which was confirmed by oral glucose tolerance tests (OGTT) in diet-induced obese C57BL/6J mice exposed to CB extract. These data suggest that steroidal glycosides 1-5 might play a role in the hepatoprotective activity of the BuOH extracts, while the results of the TC measurements and OGTT study indicate that other constituents present in the CB extract are responsible for its hypocholesterolemic and hypoglycemic activity. KEYWORDS: Easter lily; Lilium longiflorum Thunb.; hepatoprotective activity; hypoglycemic activity; steroidal glycoside PMID: 26491954 DOI: 10.1021/acs.jafc.5b04078 [Indexed for MEDLINE]

Helleborus purpurascens-Amino Acid and Peptide Analysis Linked to the Chemical and Antiproliferative Properties of the Extracted Compounds.

Molecules. 2015 Dec 11;20(12):22170-87. doi: 10.3390/molecules201219819. Segneanu AE1,2, Grozescu I3,4, Cziple F5, Berki D6, Damian D7,8, Niculite CM9,10, Florea A11,12, Leabu M13,14. Author information 1 National Institute for Research and Development in Electrochemistry and Condensed Matter-INCEMC, Timisoara 300224, Romania. 2 University Politehnica Timisoara, 2 Piata Victoriei, Timisoara 300006, Romania. 3 National Institute for Research and Development in Electrochemistry and Condensed Matter-INCEMC, Timisoara 300224, Romania. 4 University Politehnica Timisoara, 2 Piata Victoriei, Timisoara 300006, Romania. 5 University "Eftimie Murgu", Resita, 1-4 Traian Vuia, Resita 320085, Romania. 6 University Politehnica Timisoara, 2 Piata Victoriei, Timisoara 300006, Romania. 7 National Institute for Research and Development in Electrochemistry and Condensed Matter-INCEMC, Timisoara 300224, Romania. 8 University Politehnica Timisoara, 2 Piata Victoriei, Timisoara 300006, Romania. 9 Department of Morphological Sciences, University of Medicine and Pharmacy "Carol Davila", 8 Eroilor Sanitari Blvd, Sector 5, Bucharest 050474, Romania. 10 "Victor Babes" National Institute of Pathology, 99-101, Splaiul Independentei, Sector 5, Bucharest 050096, Romania. 11 Department of Morphological Sciences, University of Medicine and Pharmacy "Carol Davila", 8 Eroilor Sanitari Blvd, Sector 5, Bucharest 050474, Romania. 12 "Victor Babes" National Institute of Pathology, 99-101, Splaiul Independentei, Sector 5, Bucharest 050096, Romania. 13 Department of Morphological Sciences, University of Medicine and Pharmacy "Carol Davila", 8 Eroilor Sanitari Blvd, Sector 5, Bucharest 050474, Romania. 14 "Victor Babes" National Institute of Pathology, 99-101, Splaiul Independentei, Sector 5, Bucharest 050096, Romania. Expression of concern in Removal of Expression of Concern: Segneanu et al. Helleborus purpurascens-Amino Acid and Peptide Analysis Linked to the Chemical and Antiproliferative Properties of the Extracted Compounds. Molecules 2015, 20, 22170-22187. [Molecules. 2018] Abstract There is a strong drive worldwide to discover and exploit the therapeutic potential of a large variety of plants. In this work, an alcoholic extract of Helleborus purpurascens (family Ranunculaceae) was investigated for the identification of amino acids and peptides with putative antiproliferative effects. In our work, a separation strategy was developed using solvents of different polarity in order to obtain active compounds. Biochemical components were characterized through spectroscopic (mass spectroscopy) and chromatographic techniques (RP-HPLC and GC-MS). The biological activity of the obtained fractions was investigated in terms of their antiproliferative effects on HeLa cells. Through this study, we report an efficient separation of bioactive compounds (amino acids and peptides) from a plant extract dependent on solvent polarity, affording fractions with unaffected antiproliferative activities. Moreover, the two biologically tested fractions exerted a major antiproliferative effect, thereby suggesting potential anticancer therapeutic activity. KEYWORDS: antiproliferative activiy; chromatographic techniques; hellebore; mass spectroscopy; thionins PMID: 26690401 DOI: 10.3390/molecules201219819 [Indexed for MEDLINE] Removal of Expression of Concern: Segneanu et al. Helleborus purpurascens-Amino Acid and Peptide Analysis Linked to the Chemical and Antiproliferative Properties of the Extracted Compounds. Molecules 2015, 20, 22170-22187. Free full text Removal of Expression of Concern: Segneanu et al. Helleborus purpurascens-Amino Acid and Peptide Analysis Linked to the Chemical and Antiproliferative Properties of the Extracted Compounds. Molecules 2015, 20, 22170-22187.

A researcher you are connected to, Maria Johanna Groot, has an article that achieved a milestone of 10’000 total views.

The Hidden Effects of Dairy Farming on Public and Environmental Health in the Netherlands, India, Ethiopia, and Uganda, Considering the Use of Antibiotics and Other Agro-chemicals Frontiers in Public Health picto-impact 10’476 total views
French Universities Cancel Subscriptions to Springer Journals Negotiations between the publisher and a national consortium of academic institutions have reached a stalemate. By Diana Kwon | March 31, 2018 FLICKR, LOUGHBOROUGH UNIVERSITY LIBRARY French research organizations and universities have cancelled their subscriptions to Springer journals, due to an impasse in fee negotiations between the publisher and, a national consortium representing more than 250 academic institutions in France. After more than a year of discussions, and SpringerNature, which publishes more than 2,000 scholarly journals belonging to Springer, Nature, and BioMedCentral, have failed to reach an agreement on subscriptions for its Springer journals. The publisher’s proposal includes an increase in prices, which the consortium refuses to accept. Although and its members were expecting the publisher to cut access to Springer journals on April 1, a SpringerNature spokesperson tells The Scientist that the publisher will continue to provide French institutions with access to its journals while discussions continue. “Springer Nature is disappointed by Couperin’s decision. . . . It is with regret that our concessions have been deemed to be insufficient,” the spokesperson writes. “[As] requested by Couperin, we are considering a further proposal and during this time access will remain open.” According to a statement published by yesterday (March 30), the consortium was pushing for a reduction in subscription costs to account for the increasing proportion of open-access articles—for which authors pay an article processing fee to publish—in Springer's journals. “The continuous increase in the share of articles published [as] open access makes it difficult to maintain a policy of increasing subscription costs,” they write (translated from French with Google Translate). “On the contrary, it justifies’s request for a price reduction.” Sandrine Malotaux, the head of’s document negotiations department, tells The Scientist in an email that subscriptions to SpringerNature’s other titles are not included in this agreement. Discussions for 2019 contract renewals, she adds, have not yet begun. See “Major German Universities Cancel Elsevier Contracts” The French stalemate is the latest in a series of disputes between publishers and universities around the world. In Germany, around 200 institutions have terminated their Elsevier subscriptions in order to put pressure on the publisher during ongoing negotiations for a new nationwide licensing agreement. Discussions between Elsevier and Project Deal, an alliance of German universities and research institutions, have made little process since they began in 2016. Subscription negotiations between library consortia and Elsevier in Finland and South Korea had also become heated, but deals in those countries were reached with the last few months. In other parts of the world, such discussions appear to be on the horizon. This February, the Canadian Association of Research Libraries, which represents more than two dozen university and national libraries in Canada, published a brief describing “unsustainable” subscription costs and calling for a “coordinated national approach” against rising journal prices. “CNRS like others is willing to have the most [smooth] negotiations possible,” Laurence El Khouri, Director of the Scientific and Technical Information Department at the French National Center for Scientific Research (CNRS), one of the organizations represented by, writes in an email to The Scientist. “Scholarly communication is getting fully digital and needs to progress and develop in all ways that addresses the way science is being done. Open access is a goal but not at any price. Access to scholarly literature must meet a good balance between costs and service.” Tags springernature, springer, science publishing, publishing, open access publishing, open access, library and Elsevier

Friday, 30 March 2018

Courtenay - a couple of weeks ago

My camera tackled early morning shots.

Joint Conference of the Society of Ethnobiology & Society for Economic Botany FOOD SECURITY, SOVEREIGNTY, & TRADITIONAL KNOWLEDGE JUNE 3–­7, 2018

Memorial Union on the UW-Madison campus Madison, Wisconsin (USA) We welcome you to join us for the 2018 Joint Conference of the Society of Ethnobiology and Society of Economic Botany. The conference will take place from June 3 – 7, 2018, in Madison, Wisconsin, with most conference events held in Memorial Union at the University of Wisconsin-Madison. The theme of 2018’s conference is Food Security, Sovereignty, & Traditional Knowledge. Our joint conference provides a wonderful opportunity to meet colleagues in your field, connect with potential research partners, and develop greater cross-cultural, cross-discipline knowledge and awareness. Conference presenters and attendees come from a variety of fields and backgrounds, including academic faculty and students, Native/Indigenous community members, government personnel, museum staff, and individuals from private consulting and nonprofit agencies. This year’s conference will include multiple days of oral presentations, breakout sessions, active/applied demonstrations, and cultural field trips. The conference will culminate in a joint banquet on Wednesday evening, and will include awards and talks from this year’s Distinguished Ethnobiologist and Distinguished Economic Botanist. Some funding support for this conference is provided by the National Science Foundation and The United States Department of Agriculture.

Society of Ethnobiology Vancouver 2019

The 2019 SoE Annual meeting will be held in Vancouver, B.C. on the University of British Columbia campus, on 8–11, May, 2019. The conference theme is "Voices" to honor ethnobiology and language, song, stories, and activism. However, all ethnobiological oral or poster submissions are welcome. Stay tuned for updates, but mark your calendar now! Questions? email:

Decent men are despondent. The men I know are livid

Una Mullally: We need to put misogyny on trial. We need men to step up and challenge their own behaviour and the behaviour of their peers about 14 hours ago Updated: about 3 hours ago Una Mullally At least a thousand people bring traffic to a standstill on Dublin's O’Connell Street during a rally in solidarity with the woman in the Belfast rape trial. Video: Kathleen Harris I’m not going to write about the verdict of the Belfast rape trial. That technical legal argument has been decided, and the law has emerged in favour of four men. But as we all know, much more was revealed throughout this trial - which has had an emotional impact on most people I know - than the verdict. There were days when I couldn’t read the reports. There were days when I did read them, and thought, “I’m just going to park that.” We compartmentalise to contain our emotions, to keep going, to stem the burgeoning overflow that can leave us in states of rage and despair. In many ways, everything is always about something else, and this trial represented so much about how women are treated. Stuart Olding’s counsel, Frank O’Donoghue QC, used the types of arguments and language that left me exasperated and sad. He asked the court if Olding was the type of guy who would commit rape, “Seriously? A man who has no history of violence on or off the field?” O’Donoghue asked the young woman why she didn’t say “help me, I’m being raped and I’m going to be raped again.” I would wonder what his behaviour was like in a nightclub in the early hours after a skinful of pints ‘Titillating sideshow’ That’s not how it works, of course, but that doesn’t matter when you’re constructing an argument in court. He called the disgusting messages the men had sent to each other “a titillating sideshow”. Let’s look at those messages, and see how they reveal what these men of “good character” think about women. “We are all top shaggers,” Olding messaged. “There was a lot of spit roast last night,” Jackson messaged. “A merry-go-round at the carnival,” Olding said. McIlroy captioned a photograph, “Love Belfast Sluts.” He also messaged a friend saying, “Pumped a bird with Jacko on Monday. Roasted her.” Those are the facts. Inside Court 12: the complete story of the Belfast rape trial Women asserting rape need better support Media appeals over reporting restrictions If any man I know spoke about a woman like that, I would find it hard to believe he respected women, that he understood women to be full and whole human beings. I would wonder about him, to be honest. I would wonder what his behaviour was like in a nightclub in the early hours after a skinful of pints. Wouldn’t you? When people tell you who they are, listen to them. When people show you who they are, believe them. “Any sluts get fucked?” one of the “lads” asked, “precious secrets,” Olding replied. Those messages tell us what those men are like. It’s right there. Some men might call that “banter”. Hundreds of people attended a rally in Belfast on Thursday to support the woman at the centre of the Belfast rape trial. Photograph: Pacemaker Hundreds of people attended a rally in Belfast on Thursday to support the woman at the centre of the Belfast rape trial. Photograph: Pacemaker The young woman sent messages too. “I am not going to the police, Going up against the Ulster rugby. Yea because that’ll work,” she texted, shortly after the incident. Another text to a friend read, “Thing is I would report it if I knew they would get done. But they won’t. And that’s just unnecessary stress for me. It will be a case of my word against theirs.” She seemed to know in the back of her mind how it would pan out. It is time now to lobby effectively for reform in trials of sexual assault. Why does it feel that in rape cases it is the alleged victim who is on trial? Decent men are despondent. The men I know are livid. They’re disgusted by those WhatsApp messages, and feel sorry for what the young woman was put through during the trial. Conversations about consent For women, our reaction vibrates so much deeper. We carry the residue of every unwanted grope, every assault, every sexual encounter that we re-evaluate in the context of contemporary conversations about consent. Educating ourselves is a positive thing, but it also brings pain and shame to the surface. There are things we want to forget, brush off, disregard, but they’re there, niggling away at us, the hollow feeling of compartmentalising, the echo of every sleazy remark and catcall. Hugh O’Laoide from Limerick expressing support for the complainant in the Belfast rape trial on O’Connell Street, Dublin. Photograph: Gareth Chaney/Collins Hugh O’Laoide from Limerick expressing support for the complainant in the Belfast rape trial on O’Connell Street, Dublin. Photograph: Gareth Chaney/Collins It is time now to lobby effectively for reform in trials of sexual assault. Why does it feel that in rape cases it is the alleged victim who is on trial? In a much broader context, we need to put misogyny on trial. We need men to step up and challenge their own behaviour and the behaviour of their peers. We need to talk about consent and stop humouring the petulant arguments against consent classes in schools and colleges. The trial occurred in the context of the #MeToo movement, and in the context of the abortion referendum campaign. Both are about women having control over their own bodies. Both are about systems that oppress women, and deem us lesser than.

Thursday, 29 March 2018

Constructing Scientific Communities ‘Wholesale poisoning by hot cross-buns’ and bizarre murders of medical men

Thu, Mar 29, 2018 2:55 pm Posted: 29 Mar 2018 01:03 AM PDT This post is contributed by Professor Sally Shuttleworth (University of Oxford). As you bite into your delicious hot cross-bun this Easter, spare a thought for the inhabitants of Inverness in 1882, who were subjected to ‘whole-sale poisoning by hot cross-buns’, with over 140 worthy citizens and children affected.[1] The Glasgow Herald reported on Easter Saturday that, ‘Good Friday of 1882 is not likely to be forgotten in Inverness….In the forenoon whole families were suddenly seized with a severe and serious illness, and the town doctors were soon in great demand. The illness manifested itself at first as a rule with giddiness and pain in the neck and limbs. The giddiness was in every case followed by severe illness and vomiting….Families here and there were prostrate, and school children were suddenly seized with sickness and were dropping in a helpless condition on the ground.[2] A subsequent medical enquiry pointed the finger at the spice in the buns as the agent of poison.[3] I picked up this item of news from the Lancet, April 22, in 1822, amidst a larger item on the insanitary conditions of bread-making in London, including one establishment where bread tins were placed over an open sewer to cool. Not to be recommended! hot cross buns “Hot Cross-Buns!” from Illustrated London News, 1861. One of the delights of reading nineteenth-century periodicals is that of sheer serendipity – you never know what you will encounter next. This item on hot-cross buns came from a section in the Lancet called ‘Annotations’ which gives a round-up of medically-related news and is a wonderful way of exploring the goings-on and concerns of the time. For the Diseases of Modern Life team, this particular day is a treasure trove capturing many of the issues we are exploring, from public and occupational health through to education, and the problems of drink and drug taking. The latter figures largely, with items on ‘The Curse of Chloral’, on Dante Rossetti’s death from this new drug; ‘Another Warning against the Use of Narcotics’ on an over-worked doctor who died from an accidental overdose of morphia which he took to get to sleep; and ‘Grocers’ Licences and Secret Drinking’, which highlighted an issue Jennifer Wallis has explored, on anxieties about alcohol licenses for grocers’ premises unleashing a wave of secret female drinking: ‘To no other members of the body politic is it so well known as to the members of our profession how the secret evils to health and morality springing from the license increase the mischievous and dangerous results from alcoholic indulgence, especially amongst the female section of the community’. The prospect that the respectable activity of grocery shopping could become a cover for illicit female drinking was clearly alarming. Occupational health was covered by an item on demonstrations by shop assistants for shorter hours: the journal supported the general aim, but disapproved of ‘mixed gatherings in Trafalgar–square’ – women breaking decorum again, and disturbing public peace. The item on education addressed the issue of the day, ‘Cramming and Forcing School Children’, expressing yet again the journal’s opposition to the excessive cramming and examining of the young: ‘It is perfectly well known to everybody who has taken the trouble to study the system of teaching and training for results – the inevitable consequence of the competition and examination mania – that education is a misnomer for the method of tuition too generally employed’. I would recommend this section to our current Secretary of State for Education as some Easter reading, while munching a hot-cross bun. By far the most bizarre item in these ‘Annotations’ comes in under the bland title, ‘A Strange Story’. It recounts ‘an extraordinary plot to murder a number of medical men in Berlin’. The plot was discovered when two accomplices went to the police. The idea was to hire rooms in various parts of town, and summon a doctor under the pretence of illness ‘and then to murder him by means of a strangling instrument’. The instrument, which the perpetrator had spent two years devising, based on ‘an old-fashioned instrument of torture preserved in one of the museums of the city’ is described in gruesome detail. Even more bizarrely, the police allowed the plot to go ahead, hiding in an adjoining room and dressing up one of their number as the intended victim, Dr Lehrs. They only intervened when the ‘half-strangled man’ knocked on the floor to summon aid. If it were not for the fact that this tale pre-dates the Sherlock Holmes stories by eleven years, I would have been tempted to think that the police had been consuming too much detective fiction. I had always assumed that the elaborate dramas of enticement, so beloved of crime writers, largely belonged to the fictional domain. Now I am not so sure. Happy Easter everyone, but beware of over-indulgence, whether of hot-cross buns, alcohol (or other stimulants), or television crime dramas! [1] ‘Annotations’, Lancet April 22, 1882, 657-664, p. 661. See also ‘The Poisoning by Hot Cross Buns’, Morning Post, Monday, April 10, 1882, p. 6. [2] ‘Alarming Occurrence in Inverness’, Glasgow Herald, Saturday April 8, 1882; also ‘The Poisoning Case in Inverness’, Glasgow Herald, Monday April 10, 1882, where the original estimate of 100 cases goes up to 140. [3] ‘Poisonous Hot-Cross Buns’, August 12, 1882, p. 284.

SUZANNA SCOTT - art - varied collection of altered coin purses

Coin Cunts: an ongoing project featuring a varied collection of altered coin purses. via @SuzannaScottArt

Urtica dioica (Stinging Nettle): A Neglected Plant With Emerging Growth Promoter/Immunostimulant Properties for Farmed Fish

Mini Review ARTICLE Front. Physiol., 26 March 2018 | Gionata De Vico1*, Vincenzo Guida2 and Francesca Carella1 1Department of Biology, University of Naples Federico II, Naples, Italy 2Calatia Agricultural Society, Caserta, Italy Urtica dioica (stinging nettle), is a perennial plant belonging to the family of Urticaceae, genus Urtica. Despite the use of nettle in folk veterinary medicine is well documented, U. dioica is today an underestimated and frequently neglected plant, considered by the contemporary agriculture as a weed to be eliminated. This mini review focus on very recent studies on dietary administration of U. dioica, both as a single herb or in combination with other herbs, to enhance growth and stimulate farmed fish immunity, thus enabling the fish to be more resistant against bacterial infections. Such an emerging feature, together with cost-effectiveness, adequate availability, and easy processing of nettle, could make this herb an excellent, inexpensive and widely used dietary supplement on intensive fish farms.

Wednesday, 28 March 2018

Hibiscus sabdariffa FAMILY NAME: Malvaceae COMMON NAME: hibiscus, roselle

Serenoa repens + selenium + lycopene vs. tadalafil 5 mg for the treatment of LUTS secondary to benign prostatic obstruction: a phase IV, non-inferiority, open label, clinical study (SPRITE Study).

BJU Int. 2018 Mar 22. doi: 10.1111/bju.14209. [Epub ahead of print] Morgia G1, Vespasiani G2, Pareo RM3, Voce S4, Madonia M5, Carini M6, Ingrassia A7, Terrone C8, Gentile M9, Carrino M10, Giannantoni A11, Blefari F12, Arnone S13, Santelli G14, Russo GI1; SPRITE investigators. Author information 1 Urology section - Department of Surgery, University of Catania, 95125, Italy. 2 Urology section - University of Tor Vergata, Rome, 00100, Italy. 3 Urology section - Regina Margherita Hospital, Rome, 00100, Italy. 4 Urology section -, Ravenna, Hospital, Ravenna, 48121, Italy. 5 Urology section - Department of Surgery,, University of Sassari, 07100, Italy. 6 Department of Urology, University of Florence, Florence, 50100, Italy. 7 Urology section, Acireale Hospital, Acireale, 95024, Italy. 8 Urology section, University of Genova, Genova, 16121, Italy. 9 Urology section, Civic Hospital, Avellino, 83100, Italy. 10 Urology section, Cardarelli Hospital, Napoli, 80017, Italy. 11 Department of Urology, University of Perugia, Perugia, 06121, Italy. 12 Urology section, Prato Hospital, Prato, 59100, Italy. 13 Urology section, Lugo of Romagna Hospital, Ravenna, 48121, Italy. 14 Urology section, Lucca Hospital, Lucca, 55100, Italy. Abstract INTRODUCTION: In this randomized, open label, not-inferior clinical study, we aimed to compare the efficacy and tolerability of Serenoa Repens (SeR) + Lycopene (Ly) + Selenium (Se) therapy versus Tadalafil 5 mg in patients affected by lower urinary tract symptoms (LUTS). METHODS: From May 2015 to January 2017, 427 patients were enrolled in 21 different centres (ISRCTN73316039). Inclusion criteria were: age between 50 and 80 years old, international prostate symptom score (IPSS) ≥ 12, peak flow ≤15 ml/s, post-void residual (PVR) <100 ml. Participants were randomized into 2 arms in a 2:1 ratio: arm A (SeR-Se-Ly 1 tablet per day for 6 months) and arm B (Tadalafil 5 mg 1 tablet per day for 6 months). The primary endpoint of the study was the non-inferiority variation of the IPSS and peak flow in Group A vs. Group B after 6 months of treatment. RESULTS: 404 patients completed the full protocol. When comparing both therapies, group A was statistically not inferior to Group B considering IPSS (-3.0 vs. - 3.0; p <0.01), IPSS-QoL (-2.0 vs. -2.0; p<0.05) and peak flow (2.0 vs. 2.0; p<0.01). We found statistically significant differences in the increase of at least 3 points of the peak flow (38.2% versus 28.1%; p = 0.04) and at least 30% of the peak-flow (39.2% versus 27.3%; p <0.01) in arm A compared to arm B. The percentage of patients with an increase of at least 3 points of the IPSS and a decrease of at least 25% of the IPSS was not statistically different between the two arms. Regarding the percentage of adverse events, 4 patients in arm A (1.44%) and 10 arm B (7.81%) (p <0.05) referred side effects. CONCLUSION: We have shown that treatment with SeR-Se-Ly was not inferior to Tadalafil 5 mg in terms of improving of IPSS and peak flow. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved. KEYWORDS: LUTS ; Benign prostatic enlargement; Tadalafil; prostate; serenoa repens PMID: 29569389 DOI: 10.1111/bju.14209

A comparative study of ranitidine and quince (Cydonia oblonga mill) sauce on gastroesophageal reflux disease (GERD) in pregnancy: a randomised, open-label, active-controlled clinical trial.

J Obstet Gynaecol. 2018 Mar 19:1-7. doi: 10.1080/01443615.2018.1431210. [Epub ahead of print] Shakeri A1, Hashempur MH2,3, Mojibian M4, Aliasl F5,6, Bioos S1, Nejatbakhsh F1. Author information 1 a Department of Persian Medicine, School of Persian Medicine , Tehran University of Medical Sciences , Tehran , Iran. 2 b Noncommunicable Diseases Research Center , Fasa University of Medical Sciences , Fasa , Iran. 3 c Essence of Parsiyan Wisdom Institute , Traditional Medicine and Medicinal Plant Incubator, Shiraz University of Medical Sciences , Shiraz , Iran. 4 d Department of Gynecology and Obstetrics, Faculty of Medicine , Shahid Sadoughi University of Medical Sciences , Yazd , Iran. 5 e School of Persian Medicine , Qom University of Medical Sciences , Qom , Iran. 6 f Department of Traditional Pharmacy, School of Persian Medicine , Tehran University of Medical Sciences , Tehran , Iran. Abstract Quince (Cydonia oblonga Mill) is a popular medicinal herb in different traditional medicines. Concentrated quince fruit extract, also known as quince sauce (QS), is traditionally used for the treatment of a variety of gastrointestinal disorders. The aim of this study was to compare the efficacy of QS versus ranitidine on gastroesophageal reflux disease (GERD) in pregnant women. We compared the efficacy of 4 weeks of ranitidine (150 mg, twice daily) with the efficacy of QS (10 mg, after meals) on 137 pregnant women with GERD. Their General Symptom Score (GSS) and Major Symptom Score (MSS) were compared at the baseline, 2 weeks and 4 weeks after intervention. After 2 weeks of the study, the mean GSS score of the QS group was significantly lower compared with the ranitidine group (p = .036). Although, the GSS value at the end of the study had no difference between groups (p = .074). However, the MSS of the different symptoms of the two groups at 2 weeks and 4 weeks had no significant differences. It seems that the efficacy of QS for the management of pregnancy-related GERD is similar to ranitidine. Impact statement What is already known on this subject? Quince is a traditional gastric tonic, an appetiser, and a remedy for nausea/vomiting and epigastric pain. Also, there are several previous positive experiences about quince products for GERD treatment. What do the results of this study add? It seems that the efficacy of QS for the management of pregnancy-related GERD is similar to ranitidine. What are the implications of these findings for clinical practice and/or further research? QS can be suggested as an alternative medicine for pregnant patients with GERD. KEYWORDS: Cydonia oblonga Mill; Gastroesophageal reflux disease; herbal medicine; pregnancy; quince; traditional Persian medicine PMID: 29553843 DOI: 10.1080/01443615.2018.1431210

Evaluation of three herbal compounds used for the management of lower urinary tract disease in healthy cats: a pilot study

J Feline Med Surg. 2017 Dec 1:1098612X17748241. doi: 10.1177/1098612X17748241. [Epub ahead of print] . Daniels M1, Bartges JW2, Raditic DM3, Marsden S4, Cox SK5, Callens AJ6. Author information 1 1 Banfield Animal Hospital, Clarksville, TN, USA. 2 2 Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, The University of Georgia, Athens, GA, USA. 3 3 Veterinary Consultant in Nutrition, Athens, GA, USA. 4 4 Edmonton Holistic Clinic, Edmonton, Alberta, Canada. 5 5 Department of Biomedical and Diagnostic Services, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN, USA. 6 6 Blue Pearl Veterinary Partners in Seattle and Renton, Seattle, WA, USA. Abstract Objectives Lower urinary tract disease (LUTD) occurs commonly in cats, and idiopathic cystitis (FIC) and urolithiasis account for >80% of cases in cats <10 years of age. Although several strategies have been recommended, a common recommendation is to induce dilute urine resulting in more frequent urination and to dilute calculogenic constituents. In addition to conventional therapy using modified diets, traditional Chinese and Western herbs have been recommended, although only one - choreito - has published data available. We evaluated three commonly used herbal treatments recommended for use in cats with LUTD: San Ren Tang, Wei Ling Tang and Alisma. We hypothesized that these three Chinese herbal preparations would induce increased urine volume, decreased urine saturation for calcium oxalate and struvite, and differences in mineral and electrolyte excretions in healthy cats. Methods Six healthy, spayed female adult cats were evaluated in a placebo-controlled, randomized, crossover design study. Cats were randomized to one of four treatments, including placebo, San Ren Tang, Wei Ling Tang or Alisma. Treatment was for 2 weeks each with a 1 week washout period between treatments. At the end of each treatment period, a 24 h urine sample was collected using modified litter boxes. Results Body weights were not different between treatments. No differences were found in 24 h urinary analyte excretions, urine volume, urine pH or urinary saturation for calcium oxalate or struvite between treatments. Conclusions and relevance The results of this study do not support the hypothesis; however, evaluation of longer-term and different dosage studies in cats with LUTD is warranted. PMID: 29256321 DOI: 10.1177/1098612X17748241

Social media, cyber-aggression and student mental health on a university campus

J Ment Health. 2018 Feb 15:1-8. doi: 10.1080/09638237.2018.1437607. [Epub ahead of print] Social media, cyber-aggression and student mental health on a university campus. Mishna F1, Regehr C1, Lacombe-Duncan A1, Daciuk J1, Fearing G1, Van Wert M1. Author information Abstract AIM: Information and communication technologies (ICTs) offer immense benefits for university students including enhancing engagement and connections with others and promoting self-directed and interactive learning. Perceived anonymity and the absence of social cues, however, may contribute to risk of interpersonal aggression. While extensive research examines bullying in child and adolescent educational settings, this study addresses a gap regarding post-secondary environments. METHODS: An internet-based survey was provided to 5004 university students to examine the nature, extent and consequences of cyber-aggression. The survey received a response from 1350 students, a response rate of 28.5%. To enable further exploration, nine focus groups and eight individual interviews were conducted. RESULTS: This exploratory study found one quarter of respondents had a private video or photo shared without their permission and 28% were sent angry, vulgar, threatening or intimating messages. Perpetrators were most likely to be a friend (50%), another student (20%) or an intimate partner (18%). Focus group data revealed risks of ICTs and the need for resources and support to address students' wellbeing in the context of cyber-aggression. CONCLUSION: Cyber-aggression is experienced by a significant minority of university students, impacting their sense of wellbeing and mental health. KEYWORDS: Cyber-aggression; college students; information and communication technologies; mental health; social media; university students PMID: 29447048 DOI: 10.1080/09638237.2018.1437607

They called my university a PhD factory – now I understand why Senior academics warned that my university cared more about cheap labour than launching academic careers. It turns out they were right Fri 23 Mar 2018 07.30 GMT Last modified on Fri 23 Mar 2018 10.46 GMT Shares 955 Comments 189 ‘PhDs drop off the end of a conveyer belt, but no one cares what happens to graduates after that.’ ‘PhDs drop off the end of a conveyer belt, but no one cares what happens to graduates after that.’ Photograph: Alamy As I reluctantly consider quitting academia after a year-long research fellowship, I find myself recalling a drug dealer’s line in the film Withnail and I: “If you’re hanging on to a rising balloon, you’re presented with a difficult decision – let go before it’s too late or hang on and keep getting higher, posing the question: how long can you keep a grip on the rope?” His words describe my dilemma: do I hold on to my dream of a permanent university lectureship or abandon it as illusory and hazardous to my mental health? I’m not, of course, the first postdoc to feel this way. As I neared the end of my doctorate in 2013, I read an essay by Rebecca Schuman, which argued that “getting a literature PhD will turn you into an emotional trainwreck, not a professor”. Her article added to an expanding genre known as quit lit, which reflects the growing disillusionment of many academics with university culture. Lecturing in a UK university is starting to feel like working for a business Read more Perusing job ads, it strikes me that lectureship vacancies are rare, in contrast to the plethora of positions for university bureaucrats. When permanent jobs come up, the ensuing feeding frenzy sees hundreds of applications from superbly qualified candidates. I’ve got peer-reviewed publications and a book contract – and so has everyone else. When I was considering whether to study for a doctorate, I heard my chosen university disparaged as a PhD factory. At the time, I took this to be a sign of efficiency. Now I understand. PhDs are manufactured; they drop off the end of a conveyer belt, but no one cares what happens to graduates after that. All universities care about are the fees paid by students and the cheap labour they provide. This is the opposite of efficiency: no factory would mindlessly churn out goods that no one wants. Even so, I began a PhD knowing that I stood a very small chance of securing a permanent academic job at the end of it. Why didn’t I quit? Undoubtedly, self-delusion played a part. Most of the other postdocs I’ve met share a similar faith in the ability of their star to ascend against the odds. A similar cognitive dissonance probably affects anyone trying to establish themselves in a ferociously competitive field. Few actors, athletes or musicians enjoy the luxury of continuous employment. It’s reasonable to assume that people who choose these occupations do so knowing that their decision entails a large element of uncertainty. In these professions – just as in academia – it’s no secret how slim the chances are of making it. We’re aware that the world doesn’t owe us a living in our dream job. You succeed if you land a permanent contract, you have failed if you remain locked into an endless cycle of postdocs But there’s one crucial difference. Permanent positions are not an embedded feature of the entertainment industry, but they are promoted – rightly or wrongly – as the ultimate goal within the academy. You succeed if you land a permanent contract, you have failed if you remain locked into an endless cycle of postdocs. Moreover, film-makers, actors, writers and musicians do not require institutional support to work. Publishing work online has never been easier, but to function effectively as an academic, you need the sanction of a university. You cannot be an academic outside of the academy. Want to get a promoted in a university? Learn the art of self-branding Anonymous academic Read more An often-repeated line is that postgraduate study doesn’t have to be vocational; it’s worth pursuing for its own merits. While this may be true, it’s also disingenuous as it doesn’t reflect the aspirations of doctoral students – the overwhelming majority of PhD students I’ve encountered desperately want a career in academia. They didn’t saddle themselves with debt because they wanted intellectual stimulation. Given university marketing departments’ desperate trumpeting of the value of “employability”, it’s surprising that taught and research postgraduate degrees seem exempt from this consideration. I’ve had a year as an academic, for which I’m grateful. I’ve got a nameplate on my door (which I intend to take with me when I leave). Do I feel like a failure? No, I did everything I reasonably could to make myself employable. But I can see that the PhD production line is broken, and it won’t be fixed any time soon.

Tuesday, 27 March 2018

A la recherche des Orchidées de Madagascar

HEALING HORSES WITH KINESIOLOGY coming to Tottenham Ontario!

This is a fun-filled practical one day workshop that will teach you a 4-step method of kinesiology or "energy testing" to give your horse the healthiest lifestyle possible. You will learn how to put together effective feed programs, choose the right supplements and resolve specific horse health conditions naturally. Whether you want to incorporate this technique into your business, learn more about natural horse health or you are trying to solve a particular problem this course will be the perfect fit for you. SEATING IS LIMITED SO GET YOUR SPOT TODAY! DATE: Saturday April 14th, 2018 TIME: 9:30 am - 4:30 am LOCATION: Tottenham, Ontario (exact location TBA upon registration) COST: $120 until Mar 30th (regular price: $150) TO REGISTER: email or call 1-800-405-6643. We can't wait to see you there! This workshop is presented by Elisha Edwards, B.Sc., MBA from Riva's Remedies. She is an organic chemist and a Natural Animal Health Consultant who bridges science and natural medicine to help all horses feel their best. Elisha has over 20 years of experience working in the natural health industry, specifically in the areas of natural medicine, nutrition, homeopathy, herbs and kinesiology

Canadian universities are failing students on sexual assault -

Use of Complementary and Alternative Medicine in Inflammatory Bowel Disease Around the World.

Gastroenterol Clin North Am. 2017 Dec;46(4):679-688. doi: 10.1016/j.gtc.2017.08.001. Zezos P1, Nguyen GC2. Author information 1 Department of Medicine, Mount Sinai Hospital Centre for Inflammatory Bowel Disease, University of Toronto, 600 University Avenue, Suite 437, Toronto, Ontario M5G 1X5, Canada. 2 Department of Medicine, Mount Sinai Hospital Centre for Inflammatory Bowel Disease, University of Toronto, 600 University Avenue, Suite 437, Toronto, Ontario M5G 1X5, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, 600 University Avenue, Suite 437, Toronto, Ontario M5G 1X5, Canada. Electronic address: Abstract Use of complementary sand alternative medicine (CAM) is common among patients with inflammatory bowel disease (IBD). CAM can be broadly categorized as whole medical systems, mind-body interventions, biologically based therapies, manipulative and body-based methods, and energy therapies. Most do not use it to treat IBD specifically, and most take it as an adjunct to conventional therapy not in place of it. However, patients are frequently uncomfortable initiating a discussion of CAM with their physicians, which may impact adherence to conventional therapy. A greater emphasis on CAM in medical education may facilitate patient-physician discussions regarding CAM. KEYWORDS: Complementary and alternative medicine; Inflammatory bowel disease; Traditional medicine PMID: 29173516 DOI: 10.1016/j.gtc.2017.08.001

Estimating large carnivore populations at global scale based on spatial predictions of density and distribution - Application to the jaguar (Panthera onca).

PLoS One. 2018 Mar 26;13(3):e0194719. doi: 10.1371/journal.pone.0194719. eCollection 2018. Jędrzejewski W1, Robinson HS2,3, Abarca M1, Zeller KA4, Velasquez G1, Paemelaere EAD2, Goldberg JF5, Payan E2, Hoogesteijn R2, Boede EO6, Schmidt K7, Lampo M1, Viloria ÁL1, Carreño R1, Robinson N8, Lukacs PM3, Nowak JJ3, Salom-Pérez R2, Castañeda F2, Boron V9, Quigley H2. Author information 1 Centro de Ecología, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas, Venezuela. 2 Panthera, New York, United States of America. 3 Wildlife Biology Program, Department of Ecosystem and Conservation Sciences, W. A. Franke College of Forestry and Conservation, University of Montana, Missoula, United States of America. 4 Department of Environmental Conservation, University of Massachusetts, Amherst, United States of America. 5 Evolution, Ecology and Organismal Biology Program, University of California, Riverside, United States of America. 6 Fundación para el Desarrollo de las Ciencias, Físicas, Matemáticas y Naturales-FUDECI, Caracas, Venezuela. 7 Mammal Research Institute, Polish Academy of Sciences, Białowieża, Poland. 8 Department of Forest Management, W.A. Franke College of Forestry and Conservation, University of Montana, Missoula, United States of America. 9 Durrell Institute of Conservation and Ecology, University of Kent, Canterbury, United Kingdom. Abstract Broad scale population estimates of declining species are desired for conservation efforts. However, for many secretive species including large carnivores, such estimates are often difficult. Based on published density estimates obtained through camera trapping, presence/absence data, and globally available predictive variables derived from satellite imagery, we modelled density and occurrence of a large carnivore, the jaguar, across the species' entire range. We then combined these models in a hierarchical framework to estimate the total population. Our models indicate that potential jaguar density is best predicted by measures of primary productivity, with the highest densities in the most productive tropical habitats and a clear declining gradient with distance from the equator. Jaguar distribution, in contrast, is determined by the combined effects of human impacts and environmental factors: probability of jaguar occurrence increased with forest cover, mean temperature, and annual precipitation and declined with increases in human foot print index and human density. Probability of occurrence was also significantly higher for protected areas than outside of them. We estimated the world's jaguar population at 173,000 (95% CI: 138,000-208,000) individuals, mostly concentrated in the Amazon Basin; elsewhere, populations tend to be small and fragmented. The high number of jaguars results from the large total area still occupied (almost 9 million km2) and low human densities (< 1 person/km2) coinciding with high primary productivity in the core area of jaguar range. Our results show the importance of protected areas for jaguar persistence. We conclude that combining modelling of density and distribution can reveal ecological patterns and processes at global scales, can provide robust estimates for use in species assessments, and can guide broad-scale conservation actions. PMID: 29579129 DOI: 10.1371/journal.pone.0194719

Not in wilderness: African vulture strongholds remain in areas with high human density.

PLoS One. 2018 Jan 31;13(1):e0190594. doi: 10.1371/journal.pone.0190594. eCollection 2018. Henriques M1,2, Granadeiro JP3, Monteiro H4, Nuno A5, Lecoq M6, Cardoso P7, Regalla A2, Catry P1. Author information 1 MARE-Marine and Environmental Sciences Centre, ISPA-Instituto Universitário, Rua Jardim do Tabaco Lisbon, Portugal. 2 IBAP-Instituto da Biodiversidade e Áreas Protegidas, Avenida Dom Settimio Arturo Ferrazzetta, Bissau, Guinea-Bissau. 3 CESAM, Departamento de Biologia Animal, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, Lisbon, Portugal. 4 Coastal Planning Office, Bairro de Belém, Bissau, Guinea-Bissau. 5 Centre for Ecology and Conservation, University of Exeter, Penryn, Cornwall, United Kingdom. 6 BirdLife International, Africa Partnership Secretariat, Dakar Fann, Senegal. 7 Bioinsight, Lda. Rua Antero de Quental, Odivelas, Portugal. Abstract Vultures constitute an important functional group in many ecosystems, providing crucial ecosystem services both in natural and humanized environments. These scavengers are facing massive declines worldwide, but in several African countries virtually nothing is known on populations' status and threats, hampering the development of adequate conservation strategies. In Guinea-Bissau, globally important populations of Hooded Necrosyrtes monachus and African white-backed vultures Gyps africanus were recently reported. Using the country as a study area, we aim to characterize human-vulture interactions in West Africa applying a multidisciplinary approach. We assessed the status and distribution of vulture populations using data from 1711 km of roadside transects, examined predictors of their distribution, and produced a nationwide population estimate for the Hooded Vulture, using an innovative method based on the relationship between the size of human population in settlements and vulture numbers. We conducted 47 stakeholder interviews to assess perceived roles played by vultures, and to investigate potential anthropogenic threats. Hooded vultures were strongly associated with high human population densities, whereas no relation was found between African white-backed and Rüppell's vultures and any of the tested predictors, which included cattle density, precipitation and Normalized Difference Vegetation Index, among others. We estimate a national population of 43347 Hooded vultures, the largest population reported in the species range. Respondents were generally aware of the services provided by vultures, especially waste and carcass removal, including in urban areas. Hunting for witchcraft and traditional medicine was the most frequently recognised threat, while poisoning was ranked as having the highest impact. We hypothesise that poisoning-related mortality may be affecting African white-backed and Rüppell's vultures' distribution and explain their scarcity in apparently highly suitable habitats. Our results suggest a mutualistic rather than a commensalistic relationship between vultures and humans, with important implications for designing and implementing conservation strategies. PMID: 29385172 PMCID: PMC5791984 DOI: 10.1371/journal.pone.0190594 [Indexed for MEDLINE] Free PMC Article

Bryonolic Acid Blocks Cancer Cell Clonogenicity and Invasiveness through the Inhibition of Fatty Acid: Cholesteryl Ester Formation.

Biomedicines. 2018 Feb 12;6(1). pii: E21. doi: 10.3390/biomedicines6010021. Free full text Khallouki F1,2,3, Owen RW4, Silvente-Poirot S5, Poirot M6. Author information 1 Division of Preventive Oncology, National Center for Tumor Diseases, Im Neuenheimer Feld 460 and German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, Heidelberg 69120, Germany. 2 Team of Endocrinology and Nutrition Physiology, Faculté des Sciences et Techniques d'Errachidia (FSTE), Université Moulay Ismail, 509, Boutalamine, Errachidia 52000, Morocco. 3 Cancer Research Center of Toulouse, Unité Mixte de Recherche (UMR) 1037 Institut National de la Santé et de la Recherche Médicale (INSERM)-University of Toulouse III, Toulouse F-31037, France. 4 Division of Preventive Oncology, National Center for Tumor Diseases, Im Neuenheimer Feld 460 and German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, Heidelberg 69120, Germany. 5 Cancer Research Center of Toulouse, Unité Mixte de Recherche (UMR) 1037 Institut National de la Santé et de la Recherche Médicale (INSERM)-University of Toulouse III, Toulouse F-31037, France. 6 Cancer Research Center of Toulouse, Unité Mixte de Recherche (UMR) 1037 Institut National de la Santé et de la Recherche Médicale (INSERM)-University of Toulouse III, Toulouse F-31037, France. Abstract Bryonolic acid (BrA) is a pentacyclic triterpene present in several plants used in African traditional medicine such as Anisophyllea dichostyla R. Br. Here we investigated the in vitro anticancer properties of BrA. We report that BrA inhibits acyl-coA: cholesterol acyl transferase (ACAT) activity in rat liver microsomes in a concentration-dependent manner, blocking the biosynthesis of the cholesterol fatty acid ester tumour promoter. We next demonstrated that BrA inhibits ACAT in intact cancer cells with an IC50 of 12.6 ± 2.4 µM. BrA inhibited both clonogenicity and invasiveness of several cancer cell lines, establishing that BrA displays specific anticancer properties. BrA appears to be more potent than the other pentacyclic triterpenes, betulinic acid and ursolic acid studied under similar conditions. The inhibitory effect of BrA was reversed by exogenous addition of cholesteryl oleate, showing that ACAT inhibition is responsible for the anticancer effect of BrA. This report reveals new anticancer properties for BrA. KEYWORDS: ChEH; cancer cell; cholesterol; cholesteryl esters; colony formation; invasiveness; metabolism; tumour promoter PMID: 29439506 DOI: 10.3390/biomedicines6010021 Free full text

When beans were the food of lust Four centuries ago, flatulent foods such as beans and chickpeas were hailed as a cure for a flagging libido. Jennifer Evans investigates our ancestors' passion for pulses (Illustration: Clair Rossiter for BBC History Magazine) April 12, 2014 at 8:00 am This article was first published in the April 2014 issue of BBC History Magazine The London Cuckold, a ballad printed between c1685 and 1688, describes a man who takes leave of his “witty Wife” to “behold the glory” of the army on campaign at nearby Hounslow Heath. On his return, unaware that his wife has been unfaithful, he is lavished with attention: “When he came home she gave him Kisses, and Sack-Posset very good, Caudles too, she never misses, for they warm and heat the Blood Such things wilt create desire, And new kindle Cupid’s Fire; These things made him kiss his Wife, And to call her Love and Life.” It’s an amusing image: the guilty wife feeding her cuckolded husband with treats intended to “kindle Cupid’s fire” – stoke amorous affection and increase arousal – to make him enamoured anew and even, perhaps, more sexually appealing. But it’s her choice of foods that is most interesting: a taste of the diverse range of putative aphrodisiacs in early modern England. Caudle, a warm drink of thin gruel mixed with wine or ale and sweetened or spiced, was believed to be arousing, as was sweet-posset, another mildly alcoholic confection. But the array of aphrodisiacs also included some surprises. Along with produce from kitchen garden and hedgerow (such as parsnips, carrots and nettles), warming spices including cinnamon, anise seed and coriander were high on the list. So were birds like pheasants and sparrows, as well as animal genitalia – the pizzle (penis) and testicles of bulls, boars, goats and stags. Yet, perhaps most surprising was the belief that flatulent foods such as beans and pulses increased libido. For early modern men and women, though, these foods were more than just sexual curiosities. They were inherently understood to be treatments for infertility, not just stimulants for increasing arousal. This understanding drew upon the medical idea that sexual desire and pleasure were fundamental to fertility – without them, conception was unlikely to occur, not least because men and women would be less likely to engage in intercourse. As the early 18th-century surgeon and medical writer John Marten argued: “God Almighty has…endured each [sex] with natural Instincts, prompting them to the use thereof with desire, in order to perpetuate the Species, by producing new Creatures to supply the room of those who are gone; without which desire, what rational Creature would have taken delight in so filthy, so contemptible and base thing as Venery [sexual intercourse] is?” Windy meats Aphrodisiacs were believed to act in several different ways. They could heat the body; they could provide nutrition for the production of seed (sperm); and they could provide salt, to make the seed more titillating. Pulses, beans and other flatulent foods were thought to mainly affect men, and to function by creating wind and inflating the body. Angus McLaren, a historian of reproduction, noted that in the early modern period men were frequently recommended flatulent foods such as apples to stimulate lust. Audrey Eccles, in her work on Tudor and Stuart obstetrics and gynaecology, identified these as a category of stimulants widely known as ‘windy meats’. Medical authors of this era explained that erection of the male genitalia was caused by a combination of factors: blood, imagination, muscles, pressure, seed and wind. Helkiah Crooke’s 1616 book, Mikrokosmographia: A Description of the Body of Man, vividly invoked the roles of blood, spirits and wind in this process: “When as in venerious appetites, the bloud & the spirits do in great quantity assemble themselves out of the veines and arteries, that member is as it were a gutte filled with winde, presently swelling and growing hard.” Though Crooke used wind as a metaphor for the biological processes occurring during arousal, he also noted later in his treatise that “the efficient cause [of an erection] is heate, spirites and winde, which fill and distend” the hollow parts of the penis. Medical writers agreed that foods releasing wind into the body enabled men to get and sustain an erection. This was important not just for the act itself, but also for ensuring that impregnation resulted. Medical doctrine explained that male seed was potent and fertile because it was hot, as well as being spirituous and salty. The heat of the seed was maintained during intercourse because it remained insulated inside the man’s body until it was placed directly into the womb or neck of the womb. As Alessandro Massaria’s medical book for women from the turn of the 17th century explained: “Another cause of barrenness, by the defect of the yard [penis], is too much weakness and tenderness thereof, so that it is not strongly enough erected, to inject the seed into the womb; for the strength and stiffness of the yard, very much conduces to conception, by reason of the forcible injection of the humane seed into the womb.” In other words, more wind meant a stiffer erection, more direct placement of seed and a better chance of conception. Wind also made seed more stimulating and more potent. Medical writers asserted that seed titillated and irritated the sensitive skin of the reproductive organs as it passed through them, causing arousal. And in his Secret Miracles of Nature (1559), Lævinus Lemnius explained that seed was made from the “windy superfluity of blood” and that foods that “will make men lusty” should create “plenty of seed, and a force of a flatulent spirit, whereby the seed may be driven forth into the Matrix [womb].” So wind enhanced both the amount and potency of the seed and the function of the male reproductive organs. Unlike categories of aphrodisiacs recommended for consumption by both men and women, these ‘windy meats’ were promoted only for men. In fact, wind and flatulence were thought to be particularly damaging to women. Philip Barrough’s 16th-century medical treatise warned that “windinesse ingendered in the wombe, doth let the fertilitie or conception, & causeth barennesse”. Jane Sharp, 17th-century author of the first female-authored midwifery manual, suggested that women should take juniper berries every morning to prevent wind from collecting in the womb and damaging fertility. Beans and pulses, particularly chickpeas, were among a host of foods identified by early modern medical authors as ‘windy meats’. Barrough, for example, argued that when a man could not fulfil his marital duties (sexually satisfy his wife and make her a mother) “windie meates are good for him, as be chiche peason, beanes, scallions [onions], leekes, the roote and seed of persneppes, pine nuttus, sweet almonds… and other such like”. The English translation of Jacques Ferrand’s 1623 treatise Erotomania similarly listed various foods he believed would, through their heat and flatulence, provoke lust, including soft eggs, pine nuts, pistachios, carrots, parsnips, onions, oysters, chestnuts and chickpeas. Herbals produced by botanical writers offered similar ideas. John Parkinson’s Theatrum Botanicum of 1640 stated that: “Cicers [chickpeas], as Galen saith, are no lesse windy meate than Beanes, but yet nourish more, they provoke venery, and is thought to increase sperme.” Another flatulent food described by botanical treatises as an aphrodisiac was the aubergine, or ‘mad apple’. “They breed much windinesse, and thereby peradventure bodily lust,” commented Parkinson. Likewise, William Salmon wrote in the early 18th century that “they yield but little Nourishment, and breed much Wind, whereby ’tis possible they may provoke Bodily Lust”. Thunder but no rain However, not all medical writers agreed that ‘windy meats’ boosted fertility. Even Lemnius stated that: “Some of our lascivious women will say, that such men that trouble their wives to no purpose, do thunder, but there follows no rain, they do not water the inward ground of the matrix. They have their veins puffed up with wind, but there wants seed.” This insinuated that wind, though allowing men to engage in sexual activity, did not enhance the quality of a man’s seed and, thus, did not improve fertility. Similarly, a late 17th‑century medical tract by Swiss physician Théophile Bonet confidently dismissed windy meats, stating: “It is commonly reported of Aphrodisiacks, that Flatus or wind is necessary to Venery: but though in Boys erection or distension of the Penis may seem from Flatus, and these may concur by accident, yet they cannot nor ought not to be reckoned among Aphrodisiacks; those things indeed that excite the Spirits stir up Venery, and so make the Seed turgid, but so do not those things that breed or excite wind.” Bonet, again, did not discount the idea that wind could cause the penis to swell, but observed that ‘windy meats’ did not improve the quality of a man’s seed, so did not deserve to be classified as sexual stimulants. These criticisms became more common as the period progressed and, by the 18th century, windy meats had lost their prestige. New understandings of the anatomy of the penis revealed that wind did not inflate the penis or enhance male potency and attention shifted to the role muscles and blood flow played in sexual abilities. Jennifer Evans is a historian at the University of Hertfordshire, with a special interest in medicine and sexual health in early modern Britain

Is it time to re-think our “Canadian” health system? U of T researchers publish Canadian health system series in The Lancet

FEBRUARY 23, 2018 Gregory Marchildon considers himself an older voice when it comes to Canadian health system scholarship so he was proud to be a co-author alongside the new and leading voices in Medicare policy analysis — including Danielle Martin and Stephanie Nixon — for a series on Canadian health care published today in The Lancet. The Lancet’s special series on Canada’s global leadership in health provides a new lens on our health system and universal health coverage also known as Medicare. It also brings attention to critical aspects of the system thatLancet Cover image need to be addressed such as disparities in Indigenous health outcomes and immigrant health as well as access to care that looks beyond current coverage to include pharmacare and better mental health services. “Canada is at a crossroads right now and fairly major renegotiation is needed between the government, health-care providers, and citizens,” said Marchildon, professor at IHPME, and founding director of the North American Observatory on Health System and Policies. This renegotiation also includes a call for reconciliation with Indigenous peoples across the country. The health system can only be reformed if there is action on addressing the social determinants of health afflicting many of our Indigenous populations. Read The Lancet: Canada’s Global Leadership on Health As patients, everyday citizens can influence policy makers with respect to their health care. As a comparative health policy expert, Marchildon remarks on the passivity of Canadian patients in contrast to their European counterparts, who are often far more demanding of not only the quality of service they receive, but also its timeliness. “In Britain, patient organizations have sprung up to encourage patient advocacy, and as a result of them voicing their demands, the U.K. government has responded by ensuring patients play a larger role in decisions about their health system,” said Marchildon. Physicians also have a role to play in moving the Canadian system forward and helping to achieve the full potential of universal health coverage. For many years the normalized role of physicians has been that of an independent contractor in a system funded by the provinces and the federal government. The lack of accountability can create barriers for improving care across the spectrum, and is explored in this Lancet series. Improving waiting times for elective or non-urgent surgeries like hip or knee replacements, require active participation on the part of physicians willing to take part in programs that will reach these goals. However, lack of incentive, motivation, and the fact that physicians remain largely independent all inhibit system reform where it is needed. U.K. family doctors are also independent contractors, notes Marchildon, but there is a greater sense of responsibility on their part to ensure continuity of care particularly when that involves handing patients over to hospitals or diagnostic clinics. Profile of Gregory Marchildon“I’m not suggesting the solution is that doctors be employed by the government, but we in Canada may have to consider an approach similar to that of other nations like the U.K, perhaps by instituting contracts between doctors and the organizations or regional health authorities in which they work to create more accountability,” said Marchildon. The series also explores many reasons for Canadian’s to feel proud of their health care system such as the fact that despite our vast geographical landscape, all 13 provinces and territories have been able to provide single-payer systems to their residents. And while this type of coverage has been largely beneficial, the system has not progressed forward for some time. “When Medicare was introduced by Tommy Douglas in the 50’s and then expanded in the 60’s to include the type of coverage we now receive, these were meant to be stages in a process of development,” said Marchildon. “We knew we needed to deal with prescription drugs, home care and dental care, but we just quit at that stage, and the system remained frozen. There have been some efforts by provinces to provide programs and subsidies but those vary. In a sense we quit building.” Marchildon blames the vacuum in policy that has allowed for cases like the Cambie Surgeries Case in BC, to unfold. If successful, the case could alter Medicare laws as we know them, allowing those with higher incomes better access or earlier access to care. “It is within the Charter of Rights for Canadians to challenge the status quo, which they are in this case because they feel the health system is failing them. We can either move forward or backward, but without government decision making, we are looking at a recipe for disaster,” said Marchildon. If we are to move forward and keep our universal health care coverage, what will be required of us all, patients, physicians, and our government, the Series asks “As we look to the future, we should always remember that provinces have the lion’s share of responsibility while the federal government plays a critical strategic role. If the two can be brought together in a more cohesive way, we can produce an extremely good system that is responsive at the local level,” said Marchildon. “But that takes leadership.”

Alcohol and dementia: a complex relationship with potential for dementia prevention

Clive BallardEmail the author Clive Ballard, Iain Lang Published: 20 February 2018 Open Access PlumX Metrics Learn more about article metrics DOI: | showArticle Info Summary Full Text References The relationship between alcohol and dementia prevention has been widely studied, but most studies have focused on the potential for modest alcohol consumption to reduce the risk of dementia. These, primarily cohort, studies have varied in terms of the types of alcohol and thresholds of consumption assessed and have typically used self-reported consumption. Nonetheless, a J-shaped relationship has been fairly consistently reported between alcohol consumption and dementia risk, with moderate consumption associated with better outcomes than heavy consumption or non-consumption, although for non-drinkers there might be other confounders.1, 2 Published studies are interesting and pose questions such as whether modest consumption of red wine could be protective as part of a Mediterranean diet.3 However, the potential for substantial alcohol consumption, equivalent to 7–8 units a day for men and 5 units a day for women in most studies, to be a substantial risk factor for dementia is often overlooked.4, 5 The effect of alcohol use disorders specifically on dementia has received very little attention, although an association with an increased risk of cognitive decline has been suggested.6 In The Lancet Public Health, Michaël Schwarzinger and colleagues7 present their findings from a large retrospective study of data from over 31 million people aged at least 20 years from the French National Hospital Discharge database, including over 1 million people with an International Classification of Diseases, tenth revision (ICD-10) diagnosis of some form of dementia. Alcohol-related brain damage or alcohol use disorders based on ICD-10 codes were recorded in more than 85 000 of those who developed dementia, with a hazard ratio greater than 3 for the association between alcohol use disorders and dementia for both sexes (3·34, 95% CI 3·28–3·41 for women and 3·36, 3·31–3·41 for men). The importance of alcohol use disorders was particularly striking in people with early-onset dementia: 57% of people with a diagnosis of early-onset dementia also had an alcohol use disorder. Schwarzinger and colleagues modelled the importance of alcohol use disorders and suggested their effect might be greater than that of recognised risk factors such as smoking, depression, and hypertension. Their study is immensely important and highlights the potential of alcohol use disorders, and possibly alcohol consumption, as modifiable risk factors for dementia prevention. Schwarzinger and colleagues discuss potential mechanisms, including a direct neurotoxic effect of ethanol and metabolites; thiamine deficiency; consequences of heavy alcohol use such as hepatic encephalopathy, epilepsy, and head injury; and increased occurrence of comorbid medical and lifestyle risk factors for dementia.4, 8 An important caveat is that people with Down's syndrome and other learning disabilities—a group at major risk of early-onset dementias—were excluded from the study. Many reports addressing dementia risk, such as the Lancet Commission on dementia prevention, intervention, and care,8 have not highlighted alcohol use disorders as a substantial attributable risk factor for dementia. The focus on the potential protective effects of modest alcohol use has probably complicated the analysis and interpretation of previous findings, and the potential importance and effect of heavy alcohol use as a modifiable risk factor for dementia has probably been overlooked. Several issues still need to be addressed. One is the relationship between alcohol use disorders and related comorbidities. Alcohol use disorders are probably associated with poor diet and lifestyle, smoking, cardiovascular comorbidity, lower adherence to medical treatments, depression, and potentially social isolation. Schwarzinger and colleagues7 used a crude, area-based measure of socioeconomic status, and exploration of this aspect of the relationship between alcohol use disorders and dementia in more detail will be important. Understanding the significance of these risk factors, and the pathways of risk impact in people with alcohol use disorders, will help us to model the attributable risk more accurately and to develop better prevention strategies for people with alcohol use disorders. Additional questions relate to the threshold of alcohol consumption and potential cross-cultural differences. In the study by Schwarzinger and colleagues, the focus was on a diagnosis of alcohol use disorders rather than a threshold of alcohol consumption: individuals with alcohol use disorders had this information captured in a hospital database, having been identified as having problems related to their alcohol use. Alcohol use disorders and alcohol consumption volumes are related but distinct, and work is needed to clarify whether there is an association of similar magnitude between alcohol consumption volumes and dementia or whether associated problems and medical and psychiatric comorbidity drive the risk. A related question is whether the importance of alcohol consumption and alcohol use disorders as a risk factor varies depending on national mean alcohol consumption; for example, France consumes 12·2 L per person per year, much higher than Italy (6·7 L per person per year) and India (4·3 L per person per year).9 Although many questions remain, several can be answered using existing data, which would provide an opportunity to refine our understanding of the pathways of modifiable risk and develop optimal prevention strategies. In our view, this evidence is robust and we should move forward with clear public health messages about the relationship between both alcohol use disorders and alcohol consumption, respectively, and dementia. Following the Rose population principle,10 we might want to consider the extent to which the growing prevalence of dementia worldwide might be curbed by reductions in population-level alcohol consumption. CB reports grants and personal fees from Acadia Pharmaceuticals and Lundbeck, and personal fees from Roche, Otusaka, Novartis, Eli Lilly, and Pfizer, outside the submitted work. IL declares no competing interests. IL's contribution was supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South West Peninsula. The views expressed are those of the authors and not necessarily those of the National Heath Service, NIHR, or Department of Health. References Anstey, KJ, Mack, HA, and Cherbuin, N. Alcohol consumption as a risk factor for dementia and cognitive decline: meta-analysis of prospective studies. Am J Geriatr Psychiatry. 2009; 17: 542–555 View in Article | Summary | Full Text | Full Text PDF | PubMed | Scopus (193) | Google Scholar Purnell, C, Gao, S, Callahan, CM, and Hendrie, HC. Cardiovascular risk factors and incident Alzheimer disease: a systematic review of the literature. Alzheimer Dis Assoc Disord. 2009; 23: 1–10 View in Article | Crossref | PubMed | Scopus (101) | Google Scholar Orgogozo, JM, Dartigues, JF, Lafont, S et al. Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area. Rev Neurol (Paris). 1997; 153: 185–192 View in Article | PubMed | Google Scholar Ballard, C, Gauthier, S, Corbett, A, Brayne, C, Aarsland, D, and Jones, E. Alzheimer's disease. Lancet. 2011; 377: 1019–1031 View in Article | Summary | Full Text | Full Text PDF | PubMed | Scopus (994) | Google Scholar Ridley, NJ, Draper, B, and Withall, A. Alcohol-related dementia: an update of the evidence. Alzheimers Res Ther. 2013; 5: 3 View in Article | Crossref | PubMed | Scopus (62) | Google Scholar Kuzma, E, Llewellyn, D, Langa, KM, Wallace, RB, and Lang, I. History of alcohol use disorders and risk of severe cognitive impairment: a 19-year prospective cohort study. Am J Geriatr Psychiatry. 2014; 22: 1047–1054 View in Article | Summary | Full Text | Full Text PDF | PubMed | Scopus (10) | Google Scholar Shwarzinger, M, Pollock, BG, Hasan, OSM, Dufouil, C, Rehm, J, and for the QalyDays Study Group. Contribution of alcohol use disorders to the burden of dementia in France 2008–13: a nationwide retrospective cohort study. (published online February 20.)Lancet Public Health. 2018; View in Article | Summary | Full Text | Full Text PDF | Scopus (1) | Google Scholar Livingston, G, Sommerlad, A, Orgeta, V et al. Dementia prevention, intervention, and care. Lancet. 2017; 390: 2673–2734 View in Article | Summary | Full Text | Full Text PDF | PubMed | Scopus (44) | Google Scholar WHO. Global status report on alcohol and health. ((accessed Feb 12, 2018).) Date: 2014 View in Article | Google Scholar Rose, G. Sick individuals and sick populations. Int J Epidemiol. 2001; 30: 427–432 View in Article | Crossref | PubMed | Google Scholar

Contribution of alcohol use disorders to the burden of dementia in France 2008–13: a nationwide retrospective cohort study

Michaël Schwarzinger, MD'Correspondence information about the author MD Michaël SchwarzingerEmail the author MD Michaël Schwarzinger, Prof Bruce G Pollock, MD, Omer S M Hasan, BA, Carole Dufouil, PhD, Prof Jürgen Rehm, PhD for the show QalyDays Study Group† †Members listed at end of paper Published: 20 February 2018 Open Access PlumX Metrics Learn more about article metrics DOI: | showArticle Info Summary Full Text Tables and Figures References Supplementary Material Summary Background Dementia is a prevalent condition, affecting 5–7% of people aged 60 years and older, and a leading cause of disability in people aged 60 years and older globally. We aimed to examine the association between alcohol use disorders and dementia risk, with an emphasis on early-onset dementia (<65 years). Methods We analysed a nationwide retrospective cohort of all adult (≥20 years) patients admitted to hospital in metropolitan France between 2008 and 2013. The primary exposure was alcohol use disorders and the main outcome was dementia, both defined by International Classification of Diseases, tenth revision discharge diagnosis codes. Characteristics of early-onset dementia were studied among prevalent cases in 2008–13. Associations of alcohol use disorders and other risk factors with dementia onset were analysed in multivariate Cox models among patients admitted to hospital in 2011–13 with no record of dementia in 2008–10. Findings Of 31 624 156 adults discharged from French hospitals between 2008 and 2013, 1 109 343 were diagnosed with dementia and were included in the analyses. Of the 57 353 (5·2%) cases of early-onset dementia, most were either alcohol-related by definition (22 338 [38·9%]) or had an additional diagnosis of alcohol use disorders (10 115 [17·6%]). Alcohol use disorders were the strongest modifiable risk factor for dementia onset, with an adjusted hazard ratio of 3·34 (95% CI 3·28–3·41) for women and 3·36 (3·31–3·41) for men. Alcohol use disorders remained associated with dementia onset for both sexes (adjusted hazard ratios >1·7) in sensitivity analyses on dementia case definition (including Alzheimer's disease) or older study populations. Also, alcohol use disorders were significantly associated with all other risk factors for dementia onset (all p<0·0001). Interpretation Alcohol use disorders were a major risk factor for onset of all types of dementia, and especially early-onset dementia. Thus, screening for heavy drinking should be part of regular medical care, with intervention or treatment being offered when necessary. Additionally, other alcohol policies should be considered to reduce heavy drinking in the general population. Funding None. Background Dementia is a clinical syndrome caused by brain damage and characterised by progressive deterioration in cognitive ability and capacity for independent living and functioning.1 It is a common condition, affecting 5–7% of people aged 60 years and older worldwide,2 and is a leading cause of disability in people aged 60 years and older.3 Several types of dementia exist; Alzheimer's disease is the most common, followed by vascular dementia and rarer types of dementia, although mixed types of dementia often coexist. Alcohol use has been associated with changes in cognitive health and dementia (appendix p 3). Briefly, the relationships between alcohol use and cognitive health in general and dementia in particular are complex.4 Most reviews point to a possible beneficial effect of light-to-moderate drinking on cognitive health. However, moderate drinking has been consistently associated with detrimental effects on brain structure,5, 6 and nearly every review describes methodological problems of underlying studies, such as inconsistent measurement of alcohol use or dementia, or both, and insufficient control of potential confounders. By contrast, heavy drinking seems detrimentally related to dementia risk, whatever the dementia type. First, ethanol and its metabolite acetaldehyde have a direct neurotoxic effect, leading to permanent structural and functional brain damage. Second, heavy drinking is associated with thiamine deficiency, leading to Wernicke–Korsakoff syndrome. Third, heavy drinking is a risk factor for other conditions that can also damage the brain, such as epilepsy, head injury, and hepatic encephalopathy in patients with cirrhotic liver disease. Fourth, heavy drinking is indirectly associated with vascular dementia because of the associations of heavy drinking with vascular risk factors such as high blood pressure, haemorrhagic stroke, atrial fibrillation, and heart failure. Finally, heavy drinking is associated with tobacco smoking, depression, and low educational attainment, which are possible risk factors for dementia. This combined evidence has led to a discussion about establishing a specific diagnosis of alcohol-related dementia;7, 8, 9 however, alcohol use was not included in the life-course model of risk factors for dementia in the recent Lancet Commission on dementia prevention, intervention, and care.1 Research in context Evidence before this study Following the PRISMA guidelines, a systematic search was done using OVID to identify all work published from 2000 to Oct 3, 2017, on MEDLINE, Embase, and PsycINFO. Reviews on the effects of alcohol use on cognitive health were identified using a combination of keywords and Medical Subject Headings terms related to alcohol use, dementia, Alzheimer's disease, brain function, memory, and cognitive health (appendix pp 3–7). 23 relevant systematic reviews were identified. For light-to-moderate drinking, most reviews reported some beneficial relationships, even though alcohol use seemed to be associated with structural brain damage at moderate levels of drinking. For heavy drinking, defined by WHO and the European Medicines Agency as drinking at least 60 g of pure alcohol per day for men and at least 40 g for women, most research pointed towards a detrimental effect of alcohol on cognitive health and an increased risk of dementia. Nearly every review describes methodological problems of underlying studies, such as under-representation of heavy drinkers in population-based cohorts; inconsistent measurement of alcohol use or dementia, or both; insufficient control of potential confounders; and insufficient consideration of sample attrition in patients with alcohol use disorders. Added value of this study Using a representative large cohort of all patients admitted to French hospitals between 2008 and 2013, we found a strong association between alcohol use disorders and dementia. Under the age of 65 years, most prevalent cases of dementia were either alcohol related by definition, or patients qualified for a diagnosis of alcohol use disorders. Alcohol use disorders contributed markedly to dementia incidence, and were associated with all types of dementia over the lifetime. Thus, heavy drinking should be considered as one of the major risk factors for this cluster of diseases. Screening, brief interventions for heavy drinking, and treatment for alcohol use disorders should be implemented to reduce the alcohol-attributable burden of dementia. This study explores the effects of alcohol use disorders on dementia onset in France. Alcohol use disorders are defined by the chronic harmful use of alcohol or alcohol dependence.10 The prevalence of alcohol use disorders in France is close to the European Union mean and markedly higher than global means.11 We examined the sex-specific effects of alcohol use disorders on early-onset dementia (<65 years),9, 12 and investigated possible effect modification by dementia type. Methods Study design The data source for this study was the French National Hospital Discharge database (Programme de Médicalisation des Systèmes d'Information), which contains all public and private claims for acute inpatient and day-case hospital admissions, post-acute care, and psychiatric care since 2008. The standardised discharge summary includes patient demographics (sex, age at entry, and postal code of residency); primary and associated discharge diagnosis codes according to the WHO International Classification of Diseases, tenth revision (ICD-10); medical procedures received; length of stay; and discharge modes (including in-hospital death). Using unique anonymous identifiers, the hospital trajectory of each patient could be traced from 2008 to 2013.13 We included all patients aged 20 years and older residing in metropolitan France who were discharged in the years 2008–13. Following ICD-10 taxonomy, we excluded all patients discharged with diseases that can lead to rare types of dementia (F02): infectious diseases including HIV/AIDS, hereditary metabolic disorders, hereditary neurological disorders including Huntington's disease, other neuro-logical disorders including Parkinson's disease, and systemic connective tissue disorders. We also excluded patients with early-life mental disorders that could increase or confound dementia diagnosis, including cerebral palsy, Down's syndrome and other learning disabilities, and schizophrenia. The full coding dictionary of exclusion criteria, dementia case definitions, and risk factors assessed before dementia onset is provided in the appendix (p 14–18). The study was approved by the French National Commission for Data Protection (CNIL DE-2015-025), who granted access to the French National Hospital Discharge database for the years 2008 to 2013. The requirement for informed consent was waived because the study used de-identified data. Procedures The primary exposure was alcohol use disorders and the main outcome was dementia. Dementia was defined by any primary or associated discharge diagnosis (ICD-10) codes labelling dementia (F00-F03, F05.1, F1x.73, or G30) or related to dementia (other degenerative diseases of the nervous system [G31], progressive vascular leukoencephalopathy [I67.3], or senility [R54]).14, 15 Dementia onset was defined by the age at first dementia diagnosis recorded from 2008 to 2013; diagnoses made before age 65 years were classed as early-onset dementia. Dementia onset was separated into three categories: alcohol-related brain damage (F10.73, G31.2); vascular dementia; and other dementia, including Alzheimer's disease. Vascular dementia was broadly defined by any record of vascular dementia, mixed dementia, or progressive vascular leukoencephalopathy as well as any dementia with a history of stroke or transient ischaemic attack.16 Alcohol use disorders were identified by two categories of discharge diagnosis (ICD-10) codes: mental and behavioural disorders due to former or current chronic harmful use of alcohol (F10.1–F10.9, Z50.2), including alcohol abstinence (F10.20–F10.23); or chronic diseases attributable to alcohol use disorders (eg, K70 for alcoholic liver disease).10 Alcohol-related conditions were Wernicke-Korsakoff syndrome, end-stage liver disease and other forms of liver cirrhosis, epilepsy, and head injury. Vascular risk factors were tobacco smoking, obesity (body-mass index ≥30 kg/m2), high blood pressure, hyperlipidaemia, and diabetes.1 Cerebrovascular diseases included haemorrhagic stroke, ischaemic stroke, a history of stroke, a history of transient ischaemic attack, and cerebrovascular diseases other than stroke, all assessed before stroke. Other cardiovascular diseases were ischaemic heart disease, peripheral arterial disease, atrial fibrillation, and heart failure. Educational level is not recorded in the standardised discharge summary. We used 5645 postal codes of residency as a proxy of educational level and for each geographical area compared the proportion of adults with no high school diploma in the fourth (≥67·9%) or third (61·3–67·8%) quartiles with others (Institut National de la Statistique et des Études Économiques, French census on Jan 1, 2011). Other established risk factors for dementia included depression and hearing loss.1 Additionally, we controlled for possible risk factors for dementia, including visual impairment that might result from retinopathy or glaucoma,1 sleep apnoea,1 and other diseases that might lead to rare types of dementia (ie, chronic kidney disease including uraemia, hypothyroidism including myxoedema, and infectious diseases of the CNS including encephalitis). Statistical analysis All analyses were stratified by sex because men have shorter life expectancy and higher incidence of almost all risk factors considered. We initially studied prevalent dementia cases in 2008–13 and the distribution of alcohol-related brain damage and other alcohol use disorders by age at dementia onset. Because dementia is often associated with long diagnosis delays and associations of risk factors with dementia could be confounded by reverse causation,17 we conservatively studied risk factors for incident dementia among patients admitted to hospital from 2011 to 2013 who had no record of dementia from 2008 to 2010.18 The effects of alcohol use disorders and other risk factors on dementia onset, overall and by type, were estimated in multivariate Cox proportional hazards models without variable selection. Age was used as the timescale to estimate adjusted hazard ratios (HRs) and 95% CIs, with follow-up starting from Jan 1, 2011 (with independent left truncation on Jan 1, 2011) until dementia onset, in-hospital death, or right-censoring at last hospital discharge from 2011 to 2013.17, 19, 20 Observed non-proportional hazards were accounted for by including all risk factors as age-varying variables; alcohol use disorders, tobacco smoking, and personal histories of conditions (head injury, stroke, transient ischaemic attack, or myocardial infarction) were considered in the risk set starting from Jan 1, 2011, and other risk factors were conservatively identified at first hospital record.17 All Cox models were stratified by patient residency area across 21 French administrative regions (Corsica was included in the Provence-Alpes-Côte d'Azur region), having received care in a teaching hospital, and the first year of hospital admission from 2008 to 2013 to account for geographical and temporal variations in alcohol use exposure and dementia diagnosis as well as possible levels of misclassification for all variables. We did several sensitivity analyses to ascertain the effects of alcohol use disorders on dementia onset. First, we used definitions of dementia restricted to primary discharge diagnosis codes of dementia; ICD-10 codes labelling dementia, overall or by dementia type (vascular dementia, Alzheimer's disease); and severity level (first diagnosis of mild cognitive impairment without or before dementia, first diagnosis of dementia at a severe stage). Second, we considered the full sample, while all exclusion criteria were introduced among previous covariates. Third, we selected study populations at older landmark ages on Jan 1, 2011 (≥45 years, ≥55 years, ≥65 years, ≥75 years, or ≥85 years). Finally, the effects of alcohol abstinence (in people with previous alcohol use disorders) and other uncontrolled alcohol use disorders on the risks for dementia onset and in-hospital death were contrasted over the lifetime by use of a third-order polynomial of age on Jan 1, 2011, in Cox models adjusted for proxy of educational level and vascular risk factors, and stratified by previous variables. We did a falsification analysis in all Cox multivariate models, which relies on disease controls selected for their unknown and therefore unlikely association with an outcome.21 If no association is found for the disease controls in a large dataset such as a national hospital discharge database, it supports the validity of the associations found for the risk factors under study. We used cancer as a control, separated into three disease categories in relation to prognosis and possible association with dementia onset: cancer or metastasis of the CNS, other non-melanoma skin cancer assessed before brain metastasis, and non-melanoma skin cancer. All analyses were done in SAS (version 9.4). Role of the funding source There was no funding source for this study. The corresponding author had full access to all the data in the study and all authors had final responsibility for the decision to submit for publication. Results Of 31 624 156 adults discharged from French hospitals from 2008 to 2013, 1 328 191 (4·2%) were diagnosed with dementia (appendix p 20). We excluded 1 066 019 patients (3·4%) with diseases that can lead to rare types of dementia or with early-life mental disorders that can increase or confound dementia diagnosis (218 848 [20·5%] dementia cases; appendix p 20). 720 215 (64·9%) of the 1 109 343 dementia cases were women (figure 1). The proportion of women increased with age at dementia onset. Conversely, 37 233 (64·9%) of the 57 353 (5·2% of total) early-onset dementia cases were men. Opens large image Figure 1 Population pyramid of dementia (A) and early-onset dementia (B), overall and by alcohol use disorders (A) Prevalent cases of dementia (n=1 109 343). (B) Prevalent cases of early-onset dementia (n=57 353). View Large Image | View Hi-Res Image | Download PowerPoint Slide 945 512 (3·1%) of 30 558 137 adults were discharged with alcohol use disorders (712 583 [5·5%] of 12 941 788 men and 232 929 [1·3%] of 17 616 349 women), of whom 816 160 (86·3%) qualified for alcohol dependency and 140 312 (14·8%) had at least one period of alcohol abstinence in 2008–13. Alcohol-related brain damage was recorded in 35 034 dementia cases and other alcohol use disorders in 52 625 (figure 1). Both conditions were more frequently recorded in men (26 084 [74·5%] and 35 006 [66·5%], respectively; p<0·0001) and accounted for 32 453 (56·6%) of 57 353 early-onset dementia cases (22 338 [38·9%] and 10 115 [17·6%], respectively). Of 8 295 081 men discharged from 2011 to 2013, 181 255 (2·2%) were newly diagnosed with dementia at a median age of 82 years (IQR 75–87; table). Alcohol use disorders were recorded in 512 473 (6·2%) men and 29 944 (16·5%) of men with dementia. Alcohol use disorders were associated with an increased risk for dementia onset among men (HR 3·36, 95% CI 3·31–3·41). Alcohol use disorders were the strongest modifiable risk factor for dementia onset in men (figure 2). Table Risk factors for dementia onset Table Thumbnail. Opens Table in new tab. Data are median (IQR) or number (%). Table shows adjusted HRs from multivariate Cox regressions for incident dementia (newly diagnosed at hospital in 2011–13 with no recorded dementia in 2008–10). Details of selection of the study population are provided in the appendix (p 20). HR=hazard ratio. Opens large image Figure 2 Potentially modifiable risk factors for dementia among men (A) and women (B) Bars are 95% CIs. View Large Image | View Hi-Res Image | Download PowerPoint Slide Regarding dementia type, 12 435 (6·9%) of 181 255 men with newly diagnosed dementia had alcohol-related brain damage at a median age of 60 years (IQR 53–69; appendix p 23). The strongest association with alcohol-related brain damage was with end-stage liver disease (3593 [28·9%], HR 27·28, 95% CI 26·00–28·61) followed by liver cirrhosis (2491 [20·0%], 23·50, 22·29–24·78). Several risk factors independently contributed to alcohol-related brain damage, in particular all alcohol-related conditions and tobacco smoking (HR >2 for all; appendix p 23). Compared with alcohol-related brain damage, dementia onset was significantly delayed in other dementia types (p<0·0001). Of 181 255 men with newly diagnosed dementia, 69 700 (38·5%; median age 82 years, IQR 77–87) had vascular dementia (appendix p 24) and 99 120 (54·7%; 83 years, 77–87) had other dementia (appendix p 25). Alcohol use disorders were more frequently recorded in vascular dementia (11·2%) than in other dementia (9·8%; p<0·0001). In multivariate Cox analyses, alcohol use disorders remained associated with an increased risk for each dementia type (vascular dementia HR 2·30, 95% CI 2·24–2·36; other dementia 2·36, 2·31–2·42). Of 11 474 359 women discharged from 2011 to 2013, 322 261 (2·8%) were newly diagnosed with dementia (table). Incidence of dementia was lower in women than men up to age 80 years (appendix p 19). Collectively, the median age at dementia onset was significantly delayed in women compared with men (85 years, IQR 80–89 vs 82 years, 75–87; p<0·0001), with significantly fewer reports of alcohol-related brain damage (4281 [1·3%] and 12 435 [6·8%], respectively) and vascular dementia (104 113 [32·3%] and 69 700 [38·5%], respectively; p<0·0001). Alcohol use disorders in women were similarly associated as in men, with an increased risk for dementia onset (HR 3·34, 95% CI 3·28–3·41) and were the strongest modifiable risk factor for dementia onset in women (figure 2). About the same independent risk factors for dementia onset were identified for both sexes (adjusted HRs >1): all alcohol-related conditions; tobacco smoking, high blood pressure, and diabetes among vascular risk factors; haemorrhagic stroke, ischaemic stroke, a history of stroke, peripheral arterial diseases (in men), atrial fibrillation, and heart failure among cardiovascular diseases; and patient residency area with less education, depression, hearing loss, chronic kidney failure, hypothyroidism, and infectious disease of the CNS among other risk factors (table). However, except for depression and hypothyroidism, alcohol use disorders and all other independent risk factors for dementia were significantly less frequently recorded in women than in men (appendix p 21). In addition, except for alcohol use disorders, atrial fibrillation, lower education attainment, and hypo-thyroidism, strengths of association of the risk factors with dementia onset were significantly different between the sexes: higher in men for alcohol-related conditions, stroke, heart failure, depression, hearing loss, and infectious diseases of the CNS; and higher in women for vascular risk factors and chronic kidney failure (table; p<0·05 for all). The main study results were generally supported by sensitivity and falsification analyses. Alcohol use disorders were strongly associated with dementia onset for any case definition of dementia (figure 3; appendix pp 27–32), and when the full sample was considered with all exclusion criteria introduced among previous covariates (appendix pp 33–34). In other sensitivity analyses in older study populations selected on Jan 1, 2011, alcohol use disorders remained strongly associated with late-onset dementia (appendix pp 35–39). Compared with uncontrolled alcohol use disorders (appendix p 40), alcohol abstinence was significantly associated with lower risks of competing mortality over the lifespan, although no risk reduction was observed for dementia onset (appendix pp 41–44). Finally, regarding the falsification analysis, none of the cancer categories was associated with dementia onset, irrespective of cancer site (table) and prognosis (appendix p 26). Opens large image Figure 3 Association of alcohol use disorders with dementia onset among men (A) and women (B) in sensitivity analyses (multivariate Cox analyses) Bars are 95% CIs. View Large Image | View Hi-Res Image | Download PowerPoint Slide Discussion In this nationwide study, we found a marked association of alcohol use disorders with all types of dementia, even after controlling for potential confounding risk factors.1 The overall HR for onset of all types of dementia was above 3·3, and for vascular and other dementia remained above 2·3 for both sexes. The association with alcohol use disorders was especially important in those with early-onset dementia, with most patients having alcohol-related brain damage or an additional diagnosis of alcohol use disorders. This finding corroborates other results, which suggested alcohol is a risk factor for early-onset dementia in men.12 The French health-care system provides not only universal, but also liberal access to hospital care with minimal out-of-pocket expenses. Consequently, more than 80% of French adults older than 65 years (50% before that age) were admitted to hospital over the 6-year study period (appendix p 45), supporting a high generalisability of the study findings to the French population18 as well as populations with similar exposure to the risk factors in general, and to alcohol use disorders in particular.11 However, several potential limitations of our study should be acknowledged, including misclassified and missing variables due to the administrative recording of data. One limitation relates to the assessment of dementia, overall and by type. Although the French claims database is subject to high levels of quality control, all ICD-10 codes of dementia recorded as secondary discharge diagnoses (except senility) would be associated with better hospital reimbursement. Indeed, only 188 841 (37·5%) of 503 516 new dementia cases were identified as the primary discharge diagnosis for both sexes (appendix p 27). However, an opportunistic, up-coding bias seems equivocal because the comparison of incidence by sex and age with the reference cohort study done in the southwest of France showed no clear differences (appendix p 19) and differences are likely to be attributed to unstable estimates caused by the small sample size in the reference cohort study (190 new dementia cases over 5 years).22 Diagnosis of dementia type remains probabilistic without brain autopsy, as is the case in most epidemiological studies. Accordingly, we included 122 903 new patients identified with ICD-10 codes related to dementia, because 37 951 (30·9%) were eventually diagnosed with ICD-10 codes labelling dementia in the follow-up.15 Because of our study aim, we unconventionally prioritised alcohol-related brain damage and vascular dementia over Alzheimer's disease. Accordingly, the proportion of vascular dementia cases recorded of the 503 516 new dementia cases almost doubled from 96 252 (19·1%) with use of ICD-10 codes for vascular dementia, a rate usually reported,23 to 173 813 (34·5%) with additional use of any record of mixed dementia or dementia with a history of stroke or transient ischaemic attack.16 However, the main study findings were corroborated in all sensitivity analyses done on dementia case definition. A second limitation relates to the identification of alcohol use disorders and other risk factors for dementia. Even though alcohol use disorders were identified by several sources of medical information including post-acute rehabilitation over 6 years, alcohol use disorders were most likely underestimated compared with prevalence estimates for France (16·7% for men and 5·4% for women).11 Alcohol use disorders are highly stigmatised,24 with low treatment rates of around 10% in Europe;25 thus, probably only the more severe cases with alcohol dependence were recorded at hospital. However, such a bias would translate into a potential under-estimation of the effect of alcohol use disorders on dementia onset.26 Similarly, vascular risk factors were probably underestimated. However, except high blood pressure,1 the effects of vascular risk factors on dementia onset are probably mediated by cerebrovascular diseases that are measured exhaustively at hospital and were adjusted for in all multivariate analyses. In this regard, we found that obesity and hyperlipidaemia were not independently associated with dementia onset, in agreement with recent reviews.27, 28 A final limitation concerns the fact that assessments using large-scale administrative databases are typically overpowered to find statistical differences,21 which is true for the French National Hospital Discharge database. However, we did a falsification analysis by adding cancer controls to all analyses. None of the cancer controls were associated with dementia onset, supporting the main study findings. Additionally, the effect sizes of alcohol use disorders on dementia onset were substantial and would have probably been significant in epidemiological studies with smaller sample sizes if patients with alcohol use disorders were included and alcohol exposure was assessed. Overall, although misclassification and missing variables might have biased our findings, these biases would have been mainly in the direction of underestimation. Findings from this nationwide study suggest that the burden of dementia attributable to alcohol is much larger than previously thought. In multivariate analyses, alcohol use disorders were the strongest modifiable risk factor for dementia onset. Additionally, although alcohol abstinence was expectedly associated with a lower risk of competing death compared with uncontrolled alcohol use disorders, the study findings show that the risk for dementia onset remained unchanged after abstinence. This finding corroborates recent results showing that alcohol use directly exerts lifelong brain damage.5, 6 Finally, alcohol use disorders were associated with all other independent risk factors for dementia onset, suggesting that alcohol use disorders contribute in many ways to the risk of dementia. In summary, our study findings support that alcohol use disorders should be recognised as a major risk factor for all types of dementia. Alcohol-related dementia should be recognised as one of the main causes of early-onset dementia.7, 8, 9 Additionally, clinicians should be better aware of the role of alcohol use disorders in dementia onset over the lifetime, which seems to be a risk factor often omitted.1 Early detection, brief interventions (ie, short, structured motivational interviews to support individuals to change alcohol-related behaviour), and treatment for alcohol dependence or less severe alcohol use disorders are effective and even cost-effective measures in primary care.29 Alcohol policy measures, such as reduction of availability, increase of taxation, and ban on advertising and marketing, have also proven to be effective and cost-effective,30 although these measures have tended not to be popular with governments. For instance, the ban on alcohol advertisements was recently repealed in France.31 If all these measures are implemented widely, they could not only reduce dementia incidence or delay dementia onset, but also reduce all alcohol-attributable morbidity and mortality.25 Contributors MS conceptualised the study, contributed to the analysis and interpretation of the data, and co-wrote the first draft of the paper. BGP and CD contributed to the clinical and epidemiological implications sections, and helped shape the overall interpretation. OSMH and JR did the systematic search and screened the results for inclusion. JR also contributed to the analysis and interpretation of the data and co-wrote the first draft of the paper. QalyDays Study Group Canada J Rehm (Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON). France S Baillot, M Schwarzinger (Translational Health Economics Network [THEN], Paris); Q Guibert, F Planchet (Université Claude Bernard Lyon 1, Institut de Science Financière et d'Assurances, Lyon); S Luchini (CNRS, GREQAM-IDEP, Marseille). Declaration of interests MS is the founder and CEO of THEN (Paris, France), which received research grants from AbbVie, Gilead, Merck, and Novartis. All other authors declare no competing interests. Supplementary Material Title Description Type Size pdf iconSupplementary appendix pdf .97 MB References Livingston, G, Sommerlad, A, Orgeta, V et al. Dementia prevention, intervention, and care. Lancet. 2017; 390: 2673–2734 View in Article | Summary | Full Text | Full Text PDF | PubMed | Scopus (44) | Google Scholar Prince, M, Bryce, R, Albanese, E, Wimo, A, Ribeiro, W, and Ferri, CP. The global prevalence of dementia: a systematic review and metaanalysis. 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