And the expected answer is ‘very’ - pedants notwithstanding. The conventional way to demonstrate this is to ask a series of questions about traits with a supposedly simple genetic basis: tongue-rolling, hitch-hiker’s thumb, direction of hair whorl, cleft chin, attached earlobes… Often a tiny square of innocent-looking paper is proffered, with instructions to place it on the tongue (rolling or otherwise); to some people it’s tasteless, while to others it’s bitter due to its content of phenylthiocarbamide, meriting a sugary antidote in the form of a Polo mint. Sometimes there’s a vase of freesias whose scent fills the air – at least, for those of us whose genes allow us to detect it. Less savoury aspects involve interrogations about the colour or the smell of a subject’s urine following the eating of beetroot or aspgus.Myths of Human Genetics website [Testing many such traits in a large group demonstrates that few people share the same combination, and emphasises how genetically different we all are. The problem is that, as John H. McDonald’s splendid  website  illustraApart from family studies, another way to investigate the genetic components of traits is to compare concordance in twins. It was Francis Galton who realised their possible value ‘to weigh in just scales the effects of Nature and Nurture’ . He sentA very simple question, as posed by the Swedish twin registry in 1961  sorts ouThe indistinguishable DNA profiles of MZ twins can pose a problem in forensic analysis. One in 300 people has such a twin, and if they leave a DNA sample at a crime scene and other evidence fails to exclude their sibling, then how do we know which is responsible? Naturally enough, witness statements can be very unreliable. In one of Galton’s case studies : ‘Two twins were fond of playing tricks, and complaints were frequently made; but the boys would never own which was the guilty one, and the complainants were never certain which of the two he was. One headmaster used to say he would never flog the innocent for the guilty, and another used to flog both’.There have been a number of real cases in which this difficulty has arisen. One comes from November 1999, when a young woman was raped in the town of Grand Rapids, Michigan; the crime was unsolved until 2004, when Jerome Cooper, in jail at the time for a sex offence, applied for parole, requiring him to provide a DNA sample. His profile was checked against a list of unsolved crimes, and matched DNA recovered from the 1999 rape. Case solved? – not quite, because of the existence of Jerome’s MZ twin brother, Tyrone, who was also in the area at the time of the rape. The practice of the first headmaster had to be followed – it was impossible to jail both brothers for the crime, so they remained free. Similar cases involved putative jewellery thief Hassan or Abbas O. in Germany, and putative rapist Darrin or Damien Fernandez in Boston.A more recent French case has been widely reported: police investigating a series of sexual assaults in Marseille arrested a 24-year-old unemployed delivery driver, but the arrestee had a twin brother (with the same non-profession), and a victim could not tell them apart. The DNA left at the crime scenes was of no use, at least as far as a conventional DNA profile was concerned. News reports [This seems a lot of money – what test can they possibly mean? Differences in copy-number of DNA sequences , or in e-9 per nucleotide per cell division [9 bp, this back-of-an-envelope calculation suggests that we expect to find ~4 such differences between the sperm samples . Having identified the variants, they could be confirmed by conventional DNA sequencing, and then typed in the crime-scene samples. Four nucleotide differences seems alarmingly few, but at only ~$6000 per high-coverage genome sequence [The zygote splits after fertilisation to give two identical single-celled proto-twins, which then undergo on average about seven cell divisions in the first week of development to give embryos each consisting of about 100 cells. In the subsequent week the primordial germ cells, which give rise to the stem cell population of spermatogenesis in each male, become detectable. So let’s take 2 × 7 as a conservative minimum number of cell divisions that clearly septe the primordial stem cell populations of each twin. Any heterozygous somatic mutations that arose during these 14 cell divisions are expected to be present in half the sperm of one twin, but absent from the other. If we carry out high-coverage whole genome sequencing from a donated sperm sample of each twin, with a mutation rate of 0.05 × 10sequence  it seemsAll the same, it’s a pity that a simpler and better-established forensic tool was not available in this case, which can answer the “how unique are you?” question in a pedant-satisfying way. The inquisitive Galton  noted th


Truman described Thomas Hart Benton, his choice to create a mural for the Truman Library in Independence, Missouri. The President’s fellow Missourian lived in Kansas City at the time, his artistic career in a slump, though his reputation as a fine muralist still intact. “I picked him,” Mr. Truman told the crowd at the mural’s dedication, “because he was the best, and this is the finest work by the best.”During work on the Library mural, the President noted that he got along with the painter, even though, he joked, “That’s hard for anyone to do.” A gifted musician, writer, and prolific lithographer, Benton was also direct, impatient, radical, and often tactless. He hated museums, professing that art works belonged in clubs and barrooms, “Anywhere anybody had time to look at ’em.” In his autobiography, he mused, “A few people have, at times, expressed a belief that I was not the most desirable kind of fellow to have around. But, all in all, my differences with the home folks, when looked at in perspective, have not amounted to much.”Born in a fiercely political family, the artist was named after his uncle Thomas Hart Benton, the first and longest serving U.S. Senator of Missouri. His father, a populist, was a member of the U.S. House of Representatives. Benton bucked family tradition and entered the Art Institute of Chicago, in 1907, aspiring to become a cartoonist. His longtime love of painting affirmed in the fine arts environment, he traveled to Paris, where he attended the Académie Julien and Académie Colarossi. He met Mexican muralist Diego Rivera and studied the masters at the Louvre, among them El Greco, whose exaggerated forms found their way into his mature style.Back in New York for the lack of funds, he explored the local scene and such prevailing styles as impressionism and synchromism, especially in the work of Stanton MacDonald-Wright, who became his friend. His career took a different turn when he joined the Navy. “The most important thing, so far, I had ever done for myself as an artist.” This work, which involved extensive documentary drafts and drawing, had an enduring effect on his style. “When I came out of the Navy after the First World War, I made up my mind that I wasn’t going to be just a studio painter, a pattern maker in the fashion then dominating the art world―as it still does. I began to think of returning to the painting of subjects, subjects with meanings, which people in general might be interested in.”Though by this time well-versed in modernism, Benton turned against it unable to embrace its “colored cubes and classic attenuations,” rejecting it as “divorced from the common ways of the day.” He moved toward naturalistic and representational work focused on the American scene. He taught at the Art Students League, instructing many who went on to become famous in their own right, not the least of them abstract expressionism icon Jackson Pollock. “Even after I had castigated his innovations and he had replied by saying I had been of value to him only as someone to react against, he kept in personal touch with me ….”American Gothic, and John Steuart Curry, who painted life in his native Kansas. Many criticized their choice of the local over the cosmopolitan, but the regionalists, particularly Benton, struggled with the notion of an authentic American voice long before New York became an art center. “You just can’t think of art in terms of progress,” Benton explained in an interview, “It is not progressive. It is just different from age to age. One age gets used to a certain kind of art form and thinks that is better, but the next age will deny that thought and go back to some older form. So I wouldn’t compare the animal paintings of the cavemen with those of our times or any other times …. We were as good, as artists, when we began our history as we are now―sometimes better.”Benton’s style, a blend of modern and academic elements, came to be known as regionalism. Others in this movement were Grant Wood, most famous for his The Social History of Missouri in Jefferson City, which Benton considered his masterpiece, were part of this resurgence, recording as they were milestones in the country’s development. Benton captured his era’s transformation from rural and agrarian to urban and industrial. He painted the growth of business and technology, and the consequent changes in the lives of the common people, in paintings of steamboats and trains, factories, logging and mining operations, offices and farmhouses. “History was not a scholarly study for me but a drama.” He was innovative, bold, outspoken, and unafraid of controversy, allowing myth to blend with observation, casting ordinary people as heroes and pioneers. “I wasn’t so much interested in famous characters as I was in Missouri and the ordinary run of Missourians that I’d known in my life.”The 1930s, a decade of unprecedented economic hardship in the United States, witnessed renewed interest in history reflected in all aspects of culture. Murals, among them Benton made a habit of gallivanting around the countryside, meeting people and sketching them and their surroundings. Later he would lay out his designs from these pencil sketches, using pen and ink to define and preserve them. These and three-dimensional clay models he created served as prototypes for oil and tempera studies and for larger compositions. While many critics objected to his subjects, bold colors, manipulated forms, or muscular style, few found fault with his compositional and architectural skills. He had a talent for incorporating multiple themes in limited space and still maintaining cohesiveness.Interior of a Farmhouse on this month’s cover offers a glimpse of the brilliant color, energy, and movement that characterize Benton’s art and the complexity and richness of his murals. The title understates this intricate composition. The farmhouse at center stage anchors a community of scenes connected by a fence here, a doorway there, an angle, a partial wall, and contains his favorite people: workers doing what they do in the kitchen, the barn, the fields, at rest. On the periphery, steamboat navigation and the wheels of industry are rolling, their ubiquitous smokestacks belching above the Missouri River. Court is in progress; a worker reads the daily news; another washes up; animals wander in and outdoors. The painter reviews American industry in the 1930s, which pulsates, as if it were a live, breathing organism itself.The values of honest living and hard labor, at the heart of Benton’s work, went hand in hand with the belief that harmony between humans and nature resided on the farm, the interior of which in this painting is not altogether filled with agrarian bliss. Despite the energy emanating from the vibrant community, there are tensions, political and ecologic undertones, part and parcel of industrialization. Benton the social historian sensed the dark side of factories and increased transportation, which he noted in palpable terms, a cloud so menacing against the pristine horizon it unfolded half way across the painting.“The yellow smoke that rubs its muzzle on the window-panes/…Let fall upon its back the soot that falls from chimneys/,” Benton’s fellow Missourian T.S. Eliot wrote prophetically in “The Love Song of J. Alfred Prufrock.” As they settle, the dark plumes from smokestacks, a fixture in the artist’s work signaling the machine’s intrusion, cause havoc in the farmhouse. “The harmony man had with his environment has broken down,” he wrote. “Now men build and operate machines they don’t understand and whose inner workings they can’t even see.”Choked by industrial and other pollution, we have come to resemble Benton’s farmhouse, an organism under stress, because “man doesn’t escape his environment.” The human lung, at the center of the body’s complex internal operations is also affected by external factors in the environment: pollution, infectious agents, allergens. These factors, along with causing many other local and global adverse effects, complicate and aggravate a host of respiratory problems from rhinovirus infection, influenza, and pneumonia, to pneumococcal disease, tuberculosis, and legionellosis, now found to spread around the community from the water tank of a paving machine. Once again, the farmhouse is threatened by what’s lurking in “The yellow fog that rubs its back upon the window-panes.”


Where Are WEEE in Africa?, a new United Nations Environment Programme (UNEP) report about waste electronic and electrical equipment—also known as WEEE, or e-waste—in Benin, Côte d’Ivoire, Ghana, Liberia, and Nigeria.Local users are now the main source of electronic waste in Africa, but illegal imports of old computers, televisions, and other electronics devices from Europe, Asia, and North America still make their way there. That’s the finding of Where Are WEEE? coauthor Mathias Schluep of Empa, the Swiss Federal Laboratories for Materials Science and Technology, says most e-waste imports into West Africa come from Europe despite the presence of efficient European recycling facilities.Under the 1989 Basel Convention on the Control of Transboundary Movements of Hazardous Wastes and Their Disposal,Local use of electronics equipment has jumped in each of the five countries, accounting for an estimated 50–85% of the e-waste reported in these countries in 2010.E-waste often ends up in informal recycling centers, where it is sorted for reuse or broken down by hand and picked clean for valuable metals, then destroyed in inefficient, toxicant-producing settings, Schluep says. Open fires are tended by children, who are paid by dealers collecting metals such as copper. Schluep says girls who sell water to the workers in these settings also are exposed to the potentially toxic by-products released from the low-temperature fires.The release of dioxins is on the rise from the burning of brominated flame retardants in plastics that house these components—dioxin emissions from cable burning in the greater Accra region, for instance, are estimated to correspond to about 0.3% of total dioxin emissions in Europe.Unscrupulous sellers can get around the Basel Convention, which targets nonsalvageable items, by labeling e-waste as goods to be resold or donated. With millions of containers passing through European ports, “it’s impossible for a port authority to check them all,” says Ruediger Kuehr, executive secretary of the Solving the e-Waste Problem (StEP) Initiative, a multistakeholder initiative that counts industry, academia, governments, and nonprofits as its members. Loopholes allow sellers to ship items classified for reuse “even though it’s simply junk,” he says, but in the countries in the UNEP report, thriving refurbishment and repair businesses are “making a living, and also want to be environmentally sound.”Eric Williams, a professor at the Golisano Institute of Sustainability at the Rochester Institute of Technology in New York, is concerned that a disconnect between recyclers in Africa and the global market prevents them from selling back to Europe. “African recyclers could probably sell circuit boards to European metals refineries for more money than they would get by recycling the boards themselves,” he says. “Presumably the reason they don’t export circuit boards to Europe is that they’re not set up as an industry that can make long-term contracts and official export agreements. If this could be fixed, then the recycling of circuit boards, at least, wouldn’t be happening in Africa.”Introducing recycling technology on a large scale would be difficult, Williams adds, because of infrastructure costs, maintenance, and a lack of other resources, including an educated workforce. Groups like Empa “can take the really bad things informal recyclers are doing and improve them,” he says, “but it will be hard to bring them up to good standards. There is no low-tech green and efficient solution to circuit board recycling.”Kuehr supports a ban of e-waste shipments from developed to developing countries but applauds reuse of equipment through a second and third life as a way to reduce electronics’ large environmental footprint, which stems from resource-intensive manufacturing processes. He says a ban on e-waste intended for reuse could increase the market for even worse substitutes: brand-new but possibly low-quality equipment with a short lifetime, which brings along its own substantial environmental impacts.Jim Puckett, cofounder of the nonprofit Basel Action Network, strongly disagrees on the value of trade bans and thinks African countries should establish legal barriers to accepting any e-waste. He also says manufacturers must take responsibility for electronics at the ends of their lives. Some manufacturers, such as Dell and Hewlett-Packard, are assisting in developing private programs to manage e-waste in Africa. “Manufacturers have to step up,” he says, and some “are starting to do so.”Africa is not alone in its growth in domestic electronics users. Research in China and Peru has documented similar trends, with a burgeoning class of people who can afford to buy new and secondhand devices. By sometime between 2016 and 2018, domestic generation of e-waste in developing countries will outstrip generation in developed countries, says Williams.


One of the first kidney grafts in the world (with short-term success), in 1953, and the first dialysis session in France, in 1955, were performed under his guidance. His achievements as a writer were at least comparable: Hamburger was awarded several important literary prizes, including prix Femina, prix Balzac and the Cino del Duca prize (1979), awarded, among others, to Jorge Luis Borges and Konrad Lorenz.Jean Hamburger (1909–1992) is considered the founder of the concept of medical intensive care , the first book dedicated to patient-physician relationship in Nephrology, written when dialysis and transplantation were becoming clinical options (1963). The themes include: the central role of the patient, who should be known by name, profession, life style, and not by disease; the importance of the setting of the care; the need for truth-telling and for leaving hope; the role of research not only in the progression of science, but also in the daily clinical practice. Actualités Néphrologiques de l’Hôpital Neker”, among the first European meetings focused on a beautiful mix of clinical and research lectures, and the image of an imposing man, almost hidden behind large eyeglasses , initially closely linked to the development of Nephrology? [Almost every nephrologist of my generation has heard of Jean Hamburger 1909–1992), one of the great masters of our discipline worldwide and the father of French Nephrology [909–1992,Grand Officier de la Légion d’honneur (great officer of the Légion d’honneur), member of the highly prestigious Académie des Sciences (Academy of Sciences), whose members are called “les immortels” the immortals, founder of la Fondation pour la Recherche Médicale  and among the first to develop the idea that research is the engine of the medical progress, he was also “Commandeur de l’Ordre des Arts et des Lettres” (Commander of the Order of Arts and Literature) [erature) .prix Femina Vacaresco for a literary essay (1972), the prix Balzac and the international Cino del Duca prize (both in 1979), awarded among others to Konrad Lorenz and Ignazio Silone, which he received the year after Leopold Sedar Senghor, the great poet from Senegal, and the year before Jorge Luis Borges [For such individuals, legends and history often merge, sometimes leading to a loss of details or to a dichotomy between different aspects of the personality. For example, probably very few nephrologists know that Jean Hamburger was awarded several important literary prizes, including the ry essay 972, the s Borges .Les Migraines, Migraines) to the world famous “Traité de néphrologie” , in the following almost 30 years, titles such as “L’Homme et les Hommes” (Man and Men), “La Raison et la Passion” (Reason and Passion), “La puissance et la fragilité” (Power and Fragility) or “Le Livre de l’aventure humaine” (Book of the Human Adventure) reveal a growing and profound interest in the fragile, complex and fascinating human condition [Hamburger’s great interest in philosophy and the human condition complements, and progressively overtakes, his long list of medical publications. The book list is impressive; while medicine dominates in the first 30 years, from 1935 : “Advice to the Medical Students in my Service” [The aim of the present paper is to offer a selected reading on the patient-physician approach, as it appears in the first part of the book that, more than all the others, represents a bridge between the essayist and the nephrologist: “Service” .mon service” can be exemplified by an image of a huge team of clinicians in front of the photographer, among which Jean Hamburger is sitting in the centre, in a discrete albeit dominating position, reported in an historical article on Kidney International [The historical context of “national . It was national ; pages 1Education is the means to face this difficult cultural evolution. The need for what is now called “Continuous Medical Education” is clearly envisaged, i.e. the importance of not leaving the updating of knowledge merely to the good will of the individual: “It became evident that post-university teaching”, characterised by being “regular, methodical, almost obligatory, duly organised”, should take the place of “fragmented, insufficient initiatives” undertaken by some well-wishing physicians or groups  novelty is in the beginning: “the first chapter for which you should establish the rules of your actions regards your relationship with the patients”. In keeping with his very inquisitive attitude, he adds: “every physician may define his personal rules on this subject. I’ll share mine with you, not because I find them untouchable, but because they will serve as the basis for reflection and I will demand that you observe them during the period you’ll be in my service.” The Cartesian master then adds: “In any case, I don’t think … it’s enough to trust one’s own instinct and love for others. On the contrary, there is the need for a technique…”.The first point is that “to understand” patients “one should clearly understand that the patient, lying in his hospital bed, has almost never the same psychological reactions as a normal person”. With this in mind, Hamburger, one of the inventors of modern technical medicine, goes as far as saying that “if we must attempt to create a psychological aid for our patients and to lessen the fear inspired by disease and death, it is not only to give them comfort and aid … but because discomfort and moral pain have the most dangerous effect on the evolution of their organic disease. The psychological medical action has to be considered as important a therapy as dietary or drug prescriptions …”.The scientific attitude and the humanistic allure are reflected in the following two major and three minor rules. “The first rule is the prohibition against pronouncing in front of a patient some words that experience indicates are possible sources of anxiety”. Interestingly, among the names not to be pronounced, such as death, cancer, coma and autopsy, there is also “lupus”, a disease whose diagnosis does not have such a completely negative meaning today .L’Equipe”. However (second minor rule), the interest in the person should respect his/her privacy, and he also warns against the use of irony or humour, too often misunderstood by the patients who hide their anxiety behind a “smiling braveness”.Three “minor rules” are mentioned as possibly neglected but surely important parts of the physician’s behaviour toward patients: calling the patients by their names and not by their diseases. “First of all, it’s important that hospitalised patients do not feel that they are anonymous and deprived of their personality: it’s a great fault to indicate the patient by the bed or room number or by the name of the disease: ‘Here is the slow endocarditis of which I spoke to you this morning’”. And he goes as far as saying that it is also wrong to say “this patient”. Patients should not only be called by surname and first name, but physicians and nurses should know that “Mr. Stephane Dubois is … an art bookbinder, that he loves his job … that he has a charming fiancée, and that he’s a passionate reader of bousculer) the administrative rules”.Attention to the family, a valuable resource in healing, is a third rule. The image is clear and sharp. Families are often important, particularly in the case of anxious patients; here the Master criticises the rigid rules “limiting the visiting hours as much as those of convicted prisoners…” and enunciates his freedom of thinking, following the example of anxious patients: “In such cases, one should not hesitate to jostle  and two very important aspects whose effect on the quality of life of hospitalised patients has only recently been acknowledged (noises and long waiting times), the first fundamental chapter of “Advice” is concluded.It gives way to more technical advice specifically focussed on diagnostic approaches, therapeutic choices and the “personal organization” of study and continuous updating, all vital elements in the development of our discipline, whose reading, albeit interesting, is relevant for the history of the technical development of Nephrology, but is devoid of the timeless message conveyed by the first chapter on the behavioural rules for a physician .Zouchy et quelques autres histoires” (“Zouchy and other stories”) [Jean Hamburger was a fascinating and complex character. There is a sort of self-portrait on the cover page of his book “tories”) . This exIn the following lines, the sick physician and the educated master, a friend of the great talents of his time , merge in the most unusual portrait of an ironic and gentle dreamer, a charming model for those among us who are presently searching for examples of how humanities and science can complement each other.“(…) Twenty-five years ago, a forced vacation had confined me to the mountains for a whole year: I started writing a work of fiction. I created some strange characters that kept me company. My hero tried to distract, during one summer, a sixteen-year-old girl, imprisoned, as I was, by the disease. He told her some extravagant tales. They amused the publisher who presently wishes to publish them. They also seduced a young seventy-year-old painter, who had obstinately continued, until recently, to mainly write theatre-plays: Eugène Ionesco. His sketches, with jubilant virtues, add an unexpected and unhoped-for supplement of dream to my characters”.The heritage of the masters is always difficult to identify, in particular when it is relatively recent and when it deals with the origins of a discipline, but can we imagine the European Nephrology without Jean Hamburger?Nephrology would have probably been named kidney medicine, under the strong influence of the American medicine, while the Greek etymology may be seen as a further witness of the strong link between humanities and medicine, of which the whole life of Jean Hamburger is an interesting example .Francophone Nephrology, Richet emphasized Jean Hamburger's role as a teacher and a founder of Nephrology [More specifically, the influence of Jean Hamburger was probably too strong to be confined to a single school. His friends and colleagues defined Hamburger as a “Cartesian Master”. This definition applies to being a Master in life  and to the strict application of logics to any type of problem-solving task. The multifaceted, controversial and rich character of the great master is evident also in the memories reported by the French and French-speaking pioneers of the following generation. One of the very first is Gabriel Richet, his first assistant and another great master of Nephrology. In a recent interview in a project on the Masters of the phrology .The French and to a large extent the whole European Nephrology was deeply influenced by the combination of the strict scientific method, grounded in a pathophysiologic logic, in the best French Cartesian tradition, and the careful observation of single cases, based, as the present paper reviews, not only on technical skills, but also on an ethical attitude and respect towards the sick persons .The author declares that he has no competing interest.The manuscript has been seen and approved by the author and it is not under consideration for publication elsewhere in a similar form, in any language.


In recent time there has been ample discussion concerning censorship of research conducted in two labs involved in avian influenza virus research. Much of the debate has centered on the question whether the methods and results should reach to open disclosure given the “dual use” nature of this research which can be used for nefarious purposes.This paper reviews the discussion to date but centers on epistemological issues associated with initial justification of this research and what this entails for continuation of this research despite US governmental biosecurity concerns. The question here is whether there was reasonable moral warrant for genetic alteration of the H5N1 influenza virus.The paper concludes with philosophical  justification for continuation of this research. The New York Times published an editorial warning of impending catastrophic harm, “an engineered doomsday”  of unusually high magnitude” . The queNature and Science editors have faced. Rather, the more fundamental question is normative, and it is grounded in the conventions of biomedical research ethics. The key question then is:The question about full or redacted publication is, of course, important to ask from the perspective of national  biosecurity policy. This policy already presupposes the legitimacy of dual use research, hence the NSABB institutional oversight in this case. Further, such policy also presupposes adequate biosafety measures in place in laboratory settings, to prevent or mitigate biologic threats to the national public health and/or national security—not to mention threats to global health and international security involving microbial agents that could be weaponized or released inadvertently into the environment. But, in present case there is at least one prior, more fundamental, question to be asked. This is not an empirical question, in the sense that one may be concerned with the success or failure of the particular research methods in use or the outcomes of this research for translational medicine, e.g., production of a vaccine or antivirals. Neither is it a question about restrictions on publication such as both Is there moral warrant in place reasonably to permit genetic alteration of the H5N1 strain of avian influenza for the purposes presented in the research protocol?This is the question engaged in the following discussion. This paper thus contributes to the NSABB call for a broad and international engagement of the issues raised by the Fouchier and Kawaoka experiments.Two studies were involved, one from a research team led by virologist Ron Fouchier at the Erasmus Medical Center in Rotterdam, Netherlands, involving genetic engineering of H5N1; the other led by virologist Yoshihiro Kawaoka of the University of Wisconsin-Madison School of Veterinary Medicine  and the University of Tokyo , this research involving H5N1-H1N1 reassortment. Both studies are sub-contracts for a National Institute of Health/National Institute for Allergy and Infectious Diseases (NIH-NIAID) grant award that established an NIAID Center of Excellence for Influenza Research and Surveillance (CEIRS), specifically a Center for Research on Influenza Pathogenesis (CRIP) at Mt. Sinai School of Medicine .a. It is claimed that ferrets provide an animal model most similar to humans for study of H5N1 disease transmission. Airborne transmission is not now a natural occurrence for H5N1 incidence in humans. Hence, the chief public health and “biosecurity” concern consequent to this research is inadvertent release of a “man-made virus” into the environment, and thus a prospective pandemic having high human mortality.These two experiments succeeded in genetically altering H5N1, with the effect in the Fouchier experiment of aerosol (airborne) transmission of the mutated virus in ferretset. al. report that the Fouchier experiment exhibited transmission “with maintenance of high pathogenicity”  identify specific mutations in HA that confer transmissibility in ferrets to H5 HA-possessing viruses.•A subset of these mutations has been detected in H5N1 viruses circulating in certain countries.•It is, therefore, imperative that these viruses are monitored closely so that eradication efforts and countermeasures (such as vaccine-strain selection) can be focused on them, should they acquire transmissibility.•Consequently the benefits of these studies—the knowledge that H5 HA-possessing viruses pose a risk and the ability to monitor them and develop countermeasures—outweigh the risks.Such is Kawaoka’s counterargument to the NSABB position. Fouchier similarly commented on his motivations, noting that, “highly respected virologists…thought until a few years ago that H5N1 could never become airborne between mammals.” Not convinced, Fouchier decided “to make a virus that is transmissible” . Furtherb where the transmission can occur from [one] generation to another” . Despite•If this virus does readily transmit between humans, just as it’s now doing between ferrets, which, to date have been the best animal model we have for predicting its performance or behavior in humans; and,•If in fact, this virus is as lethal in humans as it is in ferrets;Then: this would be as serious an infectious disease encounter that the human population has ever known…••So we cannot afford to be even a little bit wrong here. Further,•If we make a mistake, the virus either gets out accidentally or it is, in fact, developed by someone who has a nefarious purpose in mind, obviously we haven’t done our job.More recently, consequent to NSABB’s decision to publish the two manuscripts without redaction, Osterholm wrote with continued objection . He voteThe foregoing represents the contour of the debate on various points of concern. Commenting on “oversight, biosafety, and biosecurity,” Fouchier’s research team continues to remind that its work has been done “completely openly” following “local, national, and international consultation.” This included consultations with biosafety officers, facility managers, and virologists operating class 3 and class 4 facilities . In addiThus, Fouchier’s team points to the normative question at issue here, and calls for a framework of reasoning, thus:If by some means, accidental or nefarious, the H5N1 laboratory mutated virus (H5N1-Mut) is released into the natural environment, how will H5N1-Mut virus behave in the natural environment? This question, q, we shall refer to as our “puzzle predicament, p.” This question is a matter of scientific prediction, itself dependent on an assortment of empirical variables.•First, there is a scientific question at issue here that is posed by the scientific and biosecurity specialists involved in this dispute: If one has a puzzle-predicamentp, givenq, then one no longer haspwhen one has a correct answer,A, toq. But, logically, “Any answer not known to be false will do, even if not known to be true”  a value short of 1 signifies a degree of (subjective) credence or epistemic support.” But, even then, one would have to consider the presumed symmetry of intuitions operative here, according to which one individual reasonably prefers to think the predictive proposition to be neither true nor false while another’s intuition is that the predictive proposition is either true or false[a iff the sentence uttered is true [false] with respect to a context of utterance and a [context of assessment]” ” .predictively, ‘tomorrow will be the end of the world’, and one believes ‘tomorrow will be the end of the world’ to be true today because one believes ‘tomorrow will prove the proposition true’, then one can say these are two beliefs which indeed one truly holds. But, these are not therefore also beliefs one knows  to be true; nor are these beliefs which one can expect others to hold to be true merely because one holds these beliefs . It can be a fact that one truly holds the two beliefs; but this fact in and of itself does not entail the yet-to-be-demonstrated claim that ‘tomorrow will be the end of the world’. By parity of reasoning, then, one would have to say the same in the case of predictive argument (beliefs) concerning the pathogenicity and transmissibility of H5N1-Mut once released into the natural environment. It is a fact that biosafety experts truly hold the belief(A) that H5N1-Mut, if accidentally or nefariously released into the environment, will have the same efficiency of transmission and the same pathogenicity in humans as that observed in ferrets. But, the fact of biosafety experts having this belief, in and of itself, does not entail the yet-to-be-demonstrated fact that, H5N1-Mut, if accidentally or nefariously released into the environment, will have the same efficiency of transmission and the same pathogenicity in humans as that observed in ferrets. And, of course, it is precisely this prospective fact that all do not want to see demonstrated, no matter the prediction.Consider, by way of illustration: If one says et. al.) and Fouchier  as utilitarians faced with the decision whether (1) to publish with redaction (such as NSABB proposed) or (2) to publish with full disclosure (such as Fouchier preferred). The former finds full publication a severe disutility, due to the prospect of accidental release and/or nefarious use of H5N1-Mut consequent to replication of the research. The latter finds full publication a significant utility, due to the prospect of improvements in knowledge in avian influenza virology and epidemiological surveillance associated with mutation of H5N1Wt, etc., based on what one may learn from continued research with H5N1-Mut. The issue here is first of all epistemic, and then, secondly, ethical. That is, one may be concerned reasonably to evaluate the rationality of the beliefs held by Osterholm and Fouchier, associated as these beliefs are with the two outcomes being debated, whatever the reliability of the predictions and the epistemic value of those predictions. One may thereafter be concerned to evaluate the ethical judgment and proposed morally warranted action that are consequents of the beliefs held. If we are to consider the beliefs rational, we expect that each scientist has either an implicit or explicit commitment to a probability measure of outcome predicted, although it is unclear whether that measure is quantitative or qualitative. NSABB’s position fails to disclose both the basis and the analysis of risk/benefit and merely expects the public at large to accept this on authority, which is unacceptable in a matter such as this one affecting the public interest.Suppose we take both Osterholm  that there is a probability of an accidental release of H5N1-Mut even as he allows for a probability of nefarious use consequent to a full disclosure of the research in an open access publication venue. But, in his case, Fouchier finds the maximal expected utility in continuing the research with open disclosure, rather than in continued research with redacted disclosure. Osterholm, in contrast, surely holds that it is rational for Fouchier and Kawaoka to conduct the research in a BSL-3 facility if he believes (as he does) that there is a probability of an accidental release of H5N1-Mut even as he allows for a probability of nefarious use consequent to full disclosure of the research in an open access publication venue. But, in his case, Osterholm finds the maximal expected utility in continuing the research but, if and only if there is redacted disclosure of the research methods. Osterholm is less concerned with the prospect of accidental release than he is with nefarious use, in which case his probability measure would have to weigh the former lower than the latter.Each of the probability measures (whatever they may be) is related to a belief that Osterholm holds and a belief that Fouchier holds. We do not say these beliefs are irrational, given the analyses of utility and disutility each has identified, as partially surveyed in the representation of the (public) debate heretofore. But, surely, one may expect that one of these two positions is Clearly, with the utilitarian/consequentialist approach to estimation of risk/benefit, we find ourselves in a continuing conundrum, without resolution of the debate in favor of either redacted disclosure such as NSABB recommended or open disclosure such as the influenza virologists preferred. Some other analytical approach is, therefore, in order. NSABB authorities would have contributed immensely to resolution of the debate more efficiently had they disclosed the basis of their risk/benefit analysis. All would likely benefit from an epistemic utility analysis that has quantitative methods in use adding to qualitative analysis. This is not the place for this exercise, especially in the absence of the data available to NSABB review. Instead, I turn to the philosopher Parfit to engage the epistemic question differently.practical reasons. One may, indeed, say that sometimes individuals (including otherwise competent scientists whose research integrity is by no means to be impugned) act on the basis of false beliefs. But, logically (according to Parfit), “if we say that false beliefs can give people reasons, we would need to add that these reasons do not have any normative force, in the sense that they do not count in favour of any act. And, we would have to ignore such reasons when we are trying to decide what someone has most reason to do”  tells me to do whatever would produce the greatest expected benefit. The expected benefit of my act is the possible benefit multiplied by the chance that my act will produce it”  five tweaks in two genes, followed by just 10 passages of the virus between ferrets, created a pathogen that could travel through the air from animal to animal. The virus remained lethal.” .bFouchier speaks of the virus being attracted to the upper respiratory tract rather than in the lung; whether the virus binds to certain mammalian receptors; whether it has to reproduce in large amounts to increase chance of transmission; whether it has to be stable in small droplets; etc., all of which variables vary yet further with “more possible mutations.” For technical comments, see E.M. Sorrell [ Sorrell . MoreoveNo financial or non-financial competing interests.


In longitudinal studies where subjects experience recurrent incidents over a period of time, such as respiratory infections, fever or diarrhea, statistical methods are required to take into account the within-subject correlation.For repeated events data with censored failure, the independent increment (AG), marginal (WLW) and conditional (PWP) models are three multiple failure models that generalize Cox’s proportional hazard model. In this paper, we revise the efficiency, accuracy and robustness of all three models under simulated scenarios with varying degrees of within-subject correlation, censoring levels, maximum number of possible recurrences and sample size. We also study the methods performance on a real dataset from a cohort study with bronchial obstruction.We find substantial differences between methods and there is not an optimal method. AG and PWP seem to be preferable to WLW for low correlation levels but the situation reverts for high correlations.All methods are stable in front of censoring, worsen with increasing recurrence levels and share a bias problem which, among other consequences, makes asymptotic normal confidence intervals not fully reliable, although they are well developed theoretically. Cox’s proportional hazards model  is the mith individual by It is common to model survival times through the hazard function. The Cox proportional hazard model for right censored survival data specifies the hazard function for the t represents time, Zi is the vector of covariates of the ith individual, β is a vector of regression coefficients and h0(t) is the so-called baseline hazard function that corresponds to the hazard function for an individual with covariables set to zero. As model (1) is formulated through the hazard function, the simulation of appropriate survival times for this model is not straightforward, the effect of the covariates must be translated from the hazards to the survival time. We need to simulate the survival times since software packages for Cox models require the individual survival time data, not the hazard function. Suppose that there are n individuals and that each individual can experience K failures. Times of failure are subject to right censoring and we consider that censoring is non informative, which means that knowledge of a censoring time for an individual or subject provides no further information about the individual’s probability of survival at a future time. Let Tij be the time when the jth failure occurs for the ith subject, measured from the subject’s study enrollment, and Ci be the corresponding censoring time for individual i. Since the jth failure time Tij is affected by right censoring we define Xij as the minimum of , i.e., Xij equals Tij if the event was observed, and Ci if it is censored. Let δij=I(Tij≤Ci) be the indicator function taking the value 1 when Tij≤Ci and 0 otherwise. For simplicity, in our simulations all censoring times are taken as constant, i.e. Ci=C for all i.where For multiple events the common approaches that generalize the Cox’s framework are the independent increment (AG), marginal (WLW) and conditional (PWP) models. These three models differ essentially in the risk sets.ith subject is assumed to follow a proportional hazard model where the hazard function is In the AG model  it is asYij(t)=I, the risk set at time t, represented by j increases, fewer individuals are likely to experience the event, but this fact does not affect the risk set due to the fact that it does not depend on j; so the coefficients estimates are stable. The AG model provides more efficient inference for a covariate effect than the plain Cox model for the time to the first event, but requires much stronger assumptions than the other models, such as independence among recurrent event times or common baseline hazards. Also, a robust “sandwich” method can be used in the estimation of standard errors =ρ0 and  so Var(gij) we proceed in the same way as before, For the gij and gi,j+1 is because w, we use that: where, Then,  And finally, w does not depend neither on k nor on c. Note that The authors declare that they have no competing interests.RV conducted literature review, wrote computer programs, produced graphs and contributed to the mathematical development. OJ developed the mathematical framework and derived mathematical results. JO contributed to the improvement of simulation techniques and software development. All authors prepared the manuscript and have read and approved the final version.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2288/13/95/prepub


This study covers the interesting field of the development in gifted children which is often neglected in pediatrics because psychomotor development data are still rare, since “gifted” children are generally noticed towards the end of their primary schooling by IQ measurement. Developmental studies have shown the evidence from several fields that children identified as “high-level potentialities” or “intellectually gifted” develop sensory, locomotor, neuropsychological, and language skills earlier than typically expected. The hypothesis is offered that the earlier development originates from biological processes affecting the physical development of the brain and in turn even intellectual abilities are developed earlier, potentially allowing for advanced development. Further it is discussed how these developmental advances interact with the social environment and in certain circumstances may entail increased risk for developing socioemotional difficulties and learning disabilities that often go unaddressed due to the masking by the advance intellectual abilities. Since the 19th century, children showing particular potential, often called “gifted”, have aroused interest among authors such as Lombrosso .  As early as 1909, Alfred Binet, the originator of the notion of “mental age,” noted schoolchildren who were “too intelligent” and who derived no benefit from education. Over the 20th century, different psychiatrists and psychologists took a particular interest in these exceptionally gifted children, in particular Terman in 1925  who cond Particularly, able children are variously referred to in the literature as “gifted,” “highly gifted,” “precocious,” “early developers,” “intellectually precocious,” “talented," “bright," “geniuses,” “prodigies,” and so forth, or as having “high-level potentialities” or “high intellectual potential”.surdoué” synonymous of exceptionally or “highly gifted” in English suggests an individual who can cope with anything (like Superman) and who is not allowed to make mistakes, or be unsuccessful, and certainly not expected to experience learning difficulties. The term “surdoué” in French or “highly gifted”, like the notion of the “gifted” child with its connotation of having received the “gift” of intelligence, can lead to rather dangerous or passionate polemics, so that we have chosen to refer to these children as having “high-level potentialities”, or in fact as being “particularly able”. Indeed, if the child naturally possesses exceptional abilities, these are not connected with learning or education, and they set the child aside, qualitatively and quantitatively, from his or her peers. Thus the child's “potentialities” refer to potential skills, talents, and abilities that can be triggered to develop in certain circumstances that relate to issues of feasibility, implementation, and motivation [ These various terms are not necessarily synonymous, since they possess differing connotations and relate to differing theoretical conceptions. “Precocious,” for instance, adds the notion of developmental dating in early childhood, restricts the notion to children, and excludes any consideration of adults. Phrases such as “intellectually precocious” or “high intellectual potential” focus solely on the intellectual domain setting aside other functions, whether bodily, praxis, or affective. The French term “tivation , 5. While various techniques are used to detect indicators of intellectual precocity , the only tool that is widely agreed upon to define this group of children is the Intelligence Quotient (IQ) which is determined from batteries of tests such as the WPPSI (Wechsler Preschool and Primary School Intelligence) scale , or the  The first intelligence tests were developed in 1905 by two French psychologists, Binet and Simon, with the creation of the first “metric scale” for intelligence. This scale was adapted in 1916 by Terman, a Californian psychologist who as early as 1922 instated the largest-ever longitudinal study on gifted children. In 1911, Stern , a Germa These scales , 7, 11 h According to the French Psychiatrist Ajuriaguerra , a “gift According to a recent report by Delaubier , commiss However, the measurement of intelligence is not sufficient on its own to predict later social or intellectual success, or the production of creative work . There a Sternberg , 19 prop In this perspective, the restriction of the term “gifted” to children obtaining a given IQ score appears as a highly arbitrary oversimplification. As a complement to the Wechsler test batteries, more focused “g-factor” tests , 21 have Certain definitions of intellectual precocity, for instance, that given in the Marland report  in the U While the classic tests such as the Wechsler tests  only measure three types of intelligence, linguistic, spatial, and logicomathematical, Gardner  in his “ Although the methods used by Gardner  are open A further dimension emerges from the scientific literature devoted to precocity and talent, and that is creativity , with a Besides the intelligence and performance tests that are in wide use to identify children with “high-level potentialities,” interviews and questionnaires are also frequently used, but they have not been subjected to any empirical validation procedure in France , whereas It has frequently been observed in intraindividual research on children with “high-level potentialities” using the Wechsler scales that differences occur between VIQ  and PIQ (performance) (12 points) although this difference is not always found to be significant . However Only complementary neuropsychological evaluations, as yet still rarely implemented, can give insight into this difference observed on certain subtests. Across the literature, it does appear that the diagnostic criteria used for identification purposes are not the subject of any consensus, and the IQ threshold score is also variable. In addition, apart from the IQ measure, there is wide variability in the complementary measures that are implemented. It is also important to take the “FLYNN effect” into account , 35 whic If according to the literature different factors are involved in the emergence of exceptional ability or talent, it has also been shown that performance is sensitive to characteristics of the socioeconomic environment –39, in p From birth, biological maturing processes are continuously at work. In the intrauterine environment, the speed of maturation of the nervous and neuromuscular systems can be modified under the influence of the environment, whether internal or external, and genetic and extracellular environmental factors can interact. These processes continue from birth, depending on individual experience within a given environment, the constraints of that environment, and the educational attitudes of the people surrounding the child .inutero, in a gradual and exponential manner, at all levels of cerebral function, in the form of neurone networks, which in each individual constitute an enrichment and a reorganisation of the repertoire of human abilities [ From birth, the sensorial and motor systems are functional to differing degrees, coming into play in a certain order ; this occurs before the maturation of the nervous system is complete. Likewise, the motor behaviours of the newborn child are initiated from fertilisation. In the course of gestation, fully operational sequences of neuromotor and sensitive-sensory movements occur. These enable the newborn child and the infant to establish more refined sensory/motor “loops” or patterns which will be progressively integrated according to the myelinisation of motor pathways, motor abilities developing interdependently with affectivity and in interaction with the environment. Sensory-motor integration is thus constructed from the start of life bilities , 8, 49 ebilities –53.  The notion of cerebral functional plasticity is important from the very start of life; there is an individual functional plasticity, providing abilities for adaptation and regulation, that makes each individual unique. In this respect, “high-level potentialities” or exceptionally able children could be seen as having all sorts of potentialities available, and this could be directly related on the one hand, to the organisation of these neurone networks functioning particularly in intermodalities and on the other hand to conduction velocity rather fast.n = 60) who at birth presented no health problem and no diagnosed pathology. It appears from this work that the particular maturity of their neuromotor and neurosensory systems and active tone enable early emergence of postural/locomotor acquisitions, hand-to-eye coordination, language acquisitions [ Psychomotor development data is still rare, since “gifted” children are generally noticed towards the end of their primary schooling by IQ measurement. In a recent French retrospective longitudinal studies , it has isitions , 54, andisitions  showed a Certain other recent studies using retrospective surveys report advances in walking and language acquisition , 56, whi The unique French longitudinal data  evidence The newborn postural responses obtained in this same study  show wel The interpretation of these advances in motor maturation among these children requires integration of several factors: the child's own motivation, his desire to make body movements, move about, acquire autonomy, or acquire power over his environment; there is also the child's environment in itself, which can encourage and provide incentive, or conversely put constraints on the child . This neuro-posturo-locomotor precocity should be distinguished from the sensory/motor advance noted in African children according to Vaivre-Douret  since thWith regard to cognitive development according to Vaivre-Douret , languag Lateral preference is established early , general Results of Vaivre-Douret's study relating to cognitive Piaget's tests such as the Casati and Lézine test  show tha With regard to executive functions , there i It is striking that in the perceptive and cognitive fields all sensory perception  appear particularly sharp, suggesting highly developed endogenous mechanisms and great receptiveness, enhancing sensory, emotional and affective reactivity, and a form of intuition functioning like a “sixth sense” thanks to intermodal abilities very sharp. With regard to cognitive functioning, excellent information-processing abilities can be noted . Analytical processes are powerful . These abilities lead to ease and speed in understanding that facilitate the working memory, immediate memory being prominent in their daily functioning, for instance in what they observe . All of this endows them with an “elephant's memory” and an “eagle eye” according to Vaivre-Douret . These children, at a very early stage, look for strategies enabling them to understand situations, a sort of self-emulation functioning within their information processing system that is essential to their personal investment, which in return enables or facilitates the implementation of a targeted function. Thus, at an early age in the course of their psychomotor development, they may go through the transitional stages of coordination by discovering for themselves the strategies to achieve them, without those around them realising it, and very quickly reach the stages of sitting, standing, and walking. They can thus appear very early on as being “into everything,” eager, and curious, for instance, taking every object apart and exhausting their parents, all the more so because they are not interested in routine activities, they prefer complex games, and later on intellectual challenges, and they enjoy brain-teasers. They are always ready to experiment and innovate, they have creative skills, in particular in construction games, and, as early as two years of age, they take an interest in life and earth sciences, astronomy, metaphysics (life and death), and in books.If the stages of sensory-motor intelligence appear to occur early in the development of gifted children, achievements measured by Piaget-type formal operational tests  appear to follow a development process that runs closer to chronological age than to mental age, according to research conducted in the 1980s –77. It t This leads us to wonder about this possible discontinuity between sensory-motor stages reached quite early by these children and the need to reach the chronological age to realise operational potential. It is around 5 to 6 years that this heterogeneity appears to come into play, and there may be links with overinvestment of an intellectual nature, at the expense, in particular, of bodily stimuli or manual activities in the physical environment. This is reinforced by the fact that the child has reached school age, when the family may be more focused on intellectual performances (such as reading). In addition, on the basis of developmental data according to Vaivre-Douret , 5, at a Among “high-level potentialities” children, if we refer to the main Freudian landmarks, the first stages of psychoaffective development come in rapid succession in “high-level potentialities” children, with a certain advance depending on the responses of the environment , 84. The With regard to sleep, significant alterations did not note to the sleeping/waking cycle according Vaivre-Douret's study . However It is important to emphasise that these “high-level potentialities” children have a highly active imagination which can rapidly become a source of anxiety if they are not reassured by their environment and if boundaries are not set. If the family and/or school environment, or some outside person, is not receptive to the child's needs and expectations—which may be completely out of step with “standard” demands—the child will show his distress or anxiety through behavioural or psychosomatic disorders, and by a lack of interest for learning, sometimes going as far as intellectual inhibition and reluctance to meet challenges. All of this leads to mental suffering of the psychoaffective type, generated by the inability to achieve fulfilment. If the environment only retains the notion of the child's advanced status in intellectual terms, drawing the child in this direction and only fuelling this aspect, and the child will become “bulimic” in proportion to his abilities to respond to this stimulation, triggering pleasure in this type of functioning which is itself reinforced by the fascination and the positive image of this pleasure experienced by the people in his environment. This happens via a form of sublimation and at the expense of his psychomotor and creative abilities, and this will lead him to isolate himself in an intellectual bubble, leaving the field open to his all-powerful imagination in a sort of “cognitive disharmony” as it has been termed by Gibello . The developmental data overall underlines the advantages of instating prophylactic guidance for “high-potential” subjects to accompany development in the psychomotor and psychological spheres. Early guidance could indeed avoid narcissistic withdrawal, behavioural deviance, and even personality problems (such as substance abuse disorders) or later decompensation episodes, in particular during adolescence, in the form of aggressiveness tending towards delinquency or depressive states accompanied by suicidal attitudes, and so forth , 49. A child carries with him an idealised self-based on parental images, but “high-level potentialities” children, who are highly empathetic, can form a hypertrophic “self-ideal” so as not to disappoint those around them and take refuge in intellectualisation. This sublimation becomes a defence mechanism against failure anxieties in case of parental inadequacy, whether conscious or unconscious. Thus, the child will renounce his emotional impulses  and his pleasures and fantasies by way of a sort of sacrifice. He will take refuge in failure or boredom, which can lead on to depression. Certain children settle into a sort of renouncement or inhibition towards play, which develops into a feeling of guilt that generates intractable anxiety. Thus, the child may organise his own neurosis as a form of defence, as seen in Rorschach's projective tests. Lebovici and Braunschweig , referri A certain amount of work in the fields of neurophysiology, neuropsychology, and anatomy affords a better understanding of the neurocognitive functioning of “high-level potentialities” children. The conduction velocity of nervous input has been studied by way of auditory stimuli, and faster transmission was shown for early developers compared with controls . According to some work, the relative and actual duration of REM sleep is greater among gifted children than among controls , 91. In  A link has been demonstrated between IQ and the “g”  intelligence factor –102. How A certain number of studies in neuropsychology backed up by cerebral imagery enhance understanding of the specific characteristics of cognitive functioning in very bright children: response in habituation tasks, for instance, is faster , 110. In Certain authors  report a Other studies in functional cerebral imagery using positron emission tomography (PET) show lower glucose consumption in the course of completion of verbal and nonverbal tasks , 132. It On the basis of our clinical experience over the last 20 years with “high-level potentialities” children, we have observed that the existence of out-of-the-ordinary cognitive abilities can also mask learning difficulties of neuropsychological  or psych More there is significant difference between VIQ and PIQ, more there are learning disabilities. In a recent study, Loureiro et al.  have sho Boys seem to be more frequently affected than girls , 58. Mal Indeed, it has not been demonstrated that prevalence of neuropsychological or neuropathological disorders among “high-potential” children is any higher than for average children , 135. Bu In attempts to describe students with learning disabilities who are gifted for example, , 137, th Development data  evidence It can be hypothesised that these specific properties play an important part in encoding for memorisation (“elephant” memories among gifted children) and thus enable specific learning abilities with sensorial or/and motor intermodalities and, then, an extensive cerebral plasticity. These learning abilities are linked to processes of sensory integration, as underlined by the work by Planche  and Gear The myelin sheath is a very good insulant for conduction, avoiding loss of the nerve input, and thus enabling the concentration of energy expenditure, which could explain the lower glucose consumption observed. This would mean that brain activity is more targeted, calling on only those regions required for processing the task, and thus decreasing energy demand in the brain metabolism, according to Neubauer . This sp The “high-level potentialities” child could thus possess a specific form of cerebral functioning with a large information processing capacity at his disposal, which gives him great flexibility, considerable advantages in terms of learning abilities, and greater cerebral plasticity than the average child.  A recent research , in addi The contributions of all the work set out in this article point to the need to conduct fine analysis of the heterogeneous cognitive profiles of “high-level potentialities” children from a very early age and to realise the importance of preserving developmental continuity for the different functions, since these can prove very vulnerable, with the risk of becoming dissociated at a later stage on account of a specific plasticity, favourable or unfavourable environments , or neuropsychological or neuropathological disorders that may develop . It is i While a biological superiority appears to occur among gifted children, favourable conditions in the child's environment  and good physical and mental health foster the realisation of the child's “high-level potentialities” or exceptional ability, and this is then accompanied by harmonious development of the personality. High-parental socioprofessional status is widely pinpointed in studies on high IQ populations , 147. MoIndeed, intellectual superiority, as Ajuriaguerra , remarke


In 1661, Kaspar Schott published his comprehensive textbook “Cursus mathematicus” in Würzburg for the first time, his “Encyclopedia of all mathematical sciences”. It was so successful that it was published again in 1674 and 1677. In its 28 books, Schott gave an introduction for beginners in 22 mathematical disciplines by means of 533 figures and numerous tables. He wanted to avoid the shortness and the unintelligibility of his predecessors Alsted and Hérigone. He cited or recommended far more than hundred authors, among them Protestants like Michael Stifel and Johannes Kepler, but also Catholics like Nicolaus Copernicus. The paper gives a survey of this work and explains especially interesting aspects: The dedication to the German emperor Leopold I., Athanasius Kircher’s letter of recommendation as well as Schott’s classification of sciences, explanations regarding geometry, astronomy, and algebra. The German Association of Mathematicians (Deutsche Mathematiker-Vereinigung) was founded in 1890. Since 1902, it has had its own seal: (Illustration The temple represents a religious context. Geometry is indispensable in the An opened book shows the Latin inscription: “Artem geometriae discere atque exercere publice interest” (“It is in public interest to learn and to practise the art of geometry”). Knobloch :34. Yet,In the first paragraph, it is stated that it is worse to extinguish a man by poison than to kill him with a sword. This seems to be a really astonishing context for geometry. The second paragraph reads: “Artem geometriae discere atque exerceri publice intersit. ars autem mathematica damnabilis interdicta est.” The first sentence is—in principle—the inscription of the German seal. The second sentence just means: “But the damnable mathematical art is forbidden.” At last the reader now recognizes that the mathematicians in this juridical text of the sixth century A.C. are the astrologers. The mathematical art is astrology.When in 1661 the German Jesuit Kaspar Schott published his mathematical textbook “Cursus mathematicus” he addressed both aspects of mathematics or—more specifically—of geometry: its great utility and the religious ideas. For him, arithmetic and geometry were the wings for the beginner (tyro) in order to penetrate the sanctuaries of mathematics (mathematicae adyta). A sanctuary (adytum) is the innermost part of a temple, strictly speaking what must not be entered, as in the case of the American Mathematical Society seal. In other words, from the very beginning, Schott put his work into a religious context.I would like to give a survey of this impressing work by dealing with four issues: (1) The work, its dedication and eulogies, (2) conception, (3) realization, (4) examples taken from the chapters on geometry, astronomy, and algebra.First of all, the title page is worth studying more diligently:  dates back to that coronation year. A crowned lady with a pair of compasses and a ruler in her left hand offers the “Cursus mathematicus” to the emperor. This emperor highly esteemed the arts and sciences and was himself a gifted musician in spite of the many wars he had still to carry on. Thanks to the insignia, the lady can be undoubtedly identified with geometry. Its crown underlines its importance. An angel holds a laurel wreath that was meant for the author of the work. We will come back to this issue in the epilogue.mathesis that is moved along below the emperor as is stated in the dedication (advolvitur). The course is originally a running, a race track.On the ground-floor, a strange vehicle is drawn by the true constellations Bear and Lion. They draw the terrestrial and the celestial globes that is the vehicle has two ‘wheels’ as in the case of Roman chariots. The armillary sphere that is a world model replaces the driver. The globes or spheres are symbolizing Schott’s The globes reveal 12 tilings of the ground-floor that is paved by squares. Nine of them can be easily identified : ballistics (warfare), military architecture (fortification), Tychonic world system, statics, gnomonics, practical geometry, algebra, geometry, and trigonometry. Obviously, the interests of an emperor being at war, shown in the armor of a knight, have influenced the selection of these nine represented mathematical disciplines out of the 22 dealt with in the volume.Utility is the leading aspect. It is not by chance that Schott will call practical geometry the noblest and most useful among all mathematical disciplines, trigonometry necessary and useful in the highest degree, gnomonics even divine.The dedication to Leopold I. contains some important hints at the work: “Regi encyclopaediam mathematicam o(ffert) d(at) c(onsecrat) Casparus Schott” .Encouraged by the emperor, Schott says, he has covered the immeasurable sea of mathematical disciplines (“immensum mathematicarum disciplinarum pelagus…percurrerem”) Schott :p.(2v°) According to Schott, the emperor knows that the mathematical sciences, combined with the experience of philosophy, are jewels in the hands of princes, kings, and emperors. Kings and monarchs of the world always attached great interest to the mathematical sciences. One might think of Alphonse the Wise of Castile or Charles the Great. Without question, in the eyes of the princes of the seventeenth century mathematics was a discipline supporting the state, it was powerful.This is demonstrated for example by Daniel Bretschneider the Elder, citizen and painter in Dresden by his “Book about various inventions” :  to the English king James, his “Astronomia nova” (“New astronomy”) and his “Astronomiae pars optica”  to the emperor Rudolph II., his “Tabulae Rudolphinae” (“Rudolfinian tables”) to the emperor Ferdinand II., the father of Leopold I.: A similar behavior is true of Clavius, Kircher, and Grégoire de Saint Vincent. But up to then nobody has dedicated a whole encyclopedia of the mathematical sciences to a sovereign. Schott’s citation of Kepler’s works should be all the more emphasized because they do not play any role in the “Mathematical course”. " (“Nothing is more beautiful than to know everything.”).Schott had inherited his yearning for universality from his Lullistic teacher Athanasius Kircher. Already his “Magia universalis naturae et artis”  whose four volumes were published between paraeneses, exhortations. He printed three of them at the beginning of his volume. One of these writings was the letter of his admired teacher Athanasius Kircher to mathematical beginners. Kircher wrote a classical enkomium, a eulogy on mathematics as we meet it again and again in the Renaissance, especially in Johannes Regiomontanus’s famous inaugural address in Padua from 1464.While Schott was elaborating his encyclopedia, he was encouraged by many contemporaries. He received officina). For a long time, the mathematical community (res publica mathematica) has waited for an author like Schott who would write a “Mathematical course”, an encyclopedia of the whole mathematics, clearly structured and based on an easy method in order to foster the scientific community (res publica litteraria) and to encourage beginners.Kircher explains that in his dialog “Symposion” Plato had Alcibiades speak of Socrates as a pharmacist’s pot. He, Kircher, preferred to compare the studies of mathematics with a workshop (sacra mathesis) (Schott divinum matheseos studium) that alone imparts recognition and knowledge of all the celestial things:Kircher speaks about the comprehensive use of the divine mathematics  Schott , p..There cannot be any doubt: Kircher and Schott following him gained their explanations from the “Prolegomena”, the preface that Christoph Clavius, chief mathematician of the Jesuits, had placed in front of his edition of Euclid’s “Elements”. God himself was the first geometer who had created the world according to arithmetical and geometrical principles.Knowledge about the world presupposed the language of mathematics. Regularity and perfection of the unchangeable, geometrical structure of the world testified for its divine origin Romano :133–178.God was the inventor of all mathematical disciplines. Schott explicitly said it in his “Horographia” (“Gnomonics”) Schott :389: “Pe ." (“The gods grant everything on the strength of pains.”). Kircher cites Epicharmus, the best known poet of the Doric comedy.This importance compensates by far for the trouble of acquiring it because: "Schott planned his textbook most carefully. He placed a preface in front of the whole work and in front of every of the 28 chapters as well. Therein he commented upon his aims and methods and defined the single mathematical, partial disciplines: a model of clarity and order!He addressed beginners and first candidates of mathematics. That he emphasized again and again. Hence, he inserted short introductions into areas or surveys of areas. He referred to further literature for additional studies. More than hundred authors are mentioned, among them Protestants like Michael Stifel or Johannes Kepler, but also Catholics like Copernicus whose theory was still rejected by the Catholic church in Schott’s time.Schott did not want to be an innovator, any more than Kepler, nor did he want to treat everything exhaustively. Here, if anywhere the wisdom proved to be true: Only when restricted does somebody prove to be a master. On the contrary, thanks to a wise self-restriction, he intended to explain the essentials in an easily comprehensible form for beginners. In his opinion, his two predecessors Johann Heinrich Alsted and Pierre Hérigone had violated this criterion. They were the only authors who had accomplished a similar work before him.Alsted’s encyclopedia comprehended the whole system of sciences in seven volumes: (Illustration varia). Mathematics is subsumed in this last group as it is indicated by the right lower picture and went short for that reason. Arithmetic, music, geometry, and astronomy are represented. Five chapters offered a medley of disciplines (farragines disciplinarum).The title page enumerates and illustrates theology, jurisprudence, medicine, philosophy, mechanics, and various subjects   Schott :261, in He likes to refer to his own books, too, for example to his “Pantometrum Kircherianum” (“Kircher’s instrument for measuring everything” 1660) or to his “Magia universalis naturae et artis”. Its third volume deals with mathematics and its fourth with physics: .Yet, Schott remained a self-critical realist and remarked  Schott gives the traditional definition of mathematics from ancient times Schott :2: “Ex hThis definition is still valid in the eighteenth century and occurs in Christian Wolff’s “Mathematisches Lexicon”  dating from 1716 Wolff :605.In view of numerous classifications of the mathematical disciplines, Schott decides on a classification that is similar to that of Clavius Schott :3: The dichotomic classification principle discrete/continuous, abstract/concrete, speculative/practical is only neglected in the case of concrete, continuous mathematics: music occurs twice. Every subdivision is divided into further subunits. It might suffice to enumerate all 22 disciplines dealt with by Schott: Arithmetic, geometry, trigonometry, astronomy, astrology, chronology, geography, navigation, gnomonics, mechanics, statics, hydrostatics, hydraulic engineering, optics, catoptrics, dioptrics, fortification, warfare, tactics, musical theory, algebra, and theory of logarithms.Apart from some few differences, this is Hérigone’s list  are geometry, geography, trigonometry, algebra, and astronomy. The shortest chapters (four to six pages) are dioptrics, statics, and tactics. Schott does not deal with theoretical arithmetic that is number theory in the sense of the Euclidean books 7–9, only with practical arithmetic. Hence this chapter comprehends only forty pages. But this first chapter was already published 1 year later, in 1662, as a book on its own and was reprinted many times in a more or less abridged version Vollrath :XII: . Thus, gnomonics is a divine science Schott :389. Thipura/mixta (pure/mixed), not on discreta/continua. The following schemes represent parts of this comprehensive classification: At the end of his work, Schott puts the synopsis of all mathematical sciences due to an author whom he is not permitted to mention Schott :611–620.Mixed mathematics is subdivided in the following way: The disciplines are again subdivided. Astronomy might serve as an example: Elements like those of Johann Vögelin, Joachim Camerarius, Jan Pietersz, Henric Coets restricted themselves to the first six books . Schott did the same in his “Geometria elementaris sive Elementorum geometricorum Euclidis sex libri primi” .Many editions of Euclid’s He believed that he had solved the famous parallel problem in the sense that he had shown that the parallel postulate is a demonstrable theorem Schott :73 “tame“If the sum of the two angles α and β is smaller than two right angles, the straight lines g, h have a point of intersection on the side of these two angles.” The inversion reads: “If the straight lines g, h have a point of intersection, the sum of the two angles α and β is smaller than two right angles.” The inversion can be indeed demonstrated and is equivalent with theorem I, 28 of Euclid’s “Elements”: , Saturn has two.The semi-Tychonic system: There is no depth of the heavens. Moon, sun, Jupiter, and Saturn turn around the earth. Mercury, Venus, and Mars turn around the sun.In theoretical astronomy, Schott explains six world systems: (Illustration Astronomia elementaris sive de sphaera mundi (Elementary astronomy or on the sphere of the world), Schott defends geocentrism concluding   Kepler .In principle, Schott explains the Ptolemaic planetary theory  that was based on excentric deferents, epicycles, equants (puncta aequantia) saying Schott :273: .subtilitas) and excellence (excellentia)  Schott .There were a second and a third edition of Schott’s textbook that appeared in 1674 and in 1677, respectively: The volume was a great success. In the seventeenth and eighteenth centuries, many similar mathematical encyclopedias followed, also by Jesuits like that of François Milliet Dechales. The mathematical method achieved great triumphs, especially in Christian Wolff’s “Elementa matheseos universae” (“Elements of the whole mathematics”) .Schott himself remained modest saying Schott :660: “NuHanc linque Sphyngem barbytos Oedipo;Vatumque sacro percitus entheoFutura praedic. HIC PERENNESCURSUS AGET TIBI SCHOTTE LAUDES.Leave this sphinx, lyre, to Oedipus;Foretell the future excited by theinspired holy action of the prophets. Thistextbook will bring you eternal glory.The Polish Jesuit and Professor of Mathematics Adam Adamandus Kochanski had sent 47 Alcaic Strophes to Schott. This meter had been introduced into Roman poetry by Horace. Such a strophe comprehends two verses, each of eleven syllables, a third consisting of nine, and a fourth verse consisting of ten syllables. Hence Kochanski spoke of Horace’s lyre. The last strophe reads Schott , p.(6vNothing has to be added to this statement.


Women with increased mammographic density (MD) have an increased risk of developing breast cancer. The purpose of our study is to evaluate an experimental method to quantify MD using a program  which measures black areas as 0, white areas as 100 and grey scale areas with intermediate values between 0 and 100, depending on the “density” of the area. Digital screening mammograms were directly estimated with this method. Initial idea and steps of the program were based on a Mac utility used by our research team.  Digital mammography has been shown to have at least equivalent diagnostic accuracy to screen–film mammography and it offers some potential advantages over conventional technology  as magniA set of fibroglandular density descriptors may be used within the text of a mammogram report, roughly corresponding to mammographic percent density (MPD) as: almost entirely fat, scattered fibroglandular densities, heterogeneously dense and extremely dense, corresponding to ≤25%, 26–50%, 51–75% and ≥76% MPD respectively , 9, 10. However, although breast density is a strong risk factor for breast cancer, no standard assessment method of MPD exists and some investigators presented their own method of density estimation , 11, 12.The purpose of this work is to evaluate an experimental method to quantify MPD using a program  specifically designed to calculate degrees of gray in mammographiesWe realized a prospective study about a method of calculation of breast mammography density. Our main purpose was to obtain an objective value of mammographic density for digital mammography and to ‘avoid’ the subjectivity of estimation. A special software , which can quantify MD, was used the estimate breast density in digital mammographies. Initial version of the program was not compatible with Windows XP , a problThe program ‘ignores’ absolutely black areas. In absolutely white areas, program estimation corresponds to one hundred. In grey scale areas the estimated values are between 0 and 100, depending on the ‘density’ of the area. Moreover, the program has the capacity to ‘surround’ the breast on the mammogram and actually to measure breast density in this particular area . InitialDigital screening mammograms from 39 patients were directly estimated with the program and compared with clinical impression, blindly estimated by the authors. Density values in mediolateraloblique mammograms were increased in comparison with craniocaudal projections, due to the major pectoralis muscle (MPM). Therefore, to avoid the ‘whiteness’ of MPM, a special ‘intrument’ of the software was used which removes the MPM, which is replaced by an absolutely black area (ΑΒΑ). Taking into account that the program ignores ABA, this area is not calculated anymore in the final estimation of breast density. Similarly, the black background of mammograms  did not lower the real density value in mammograms, because as already mentioned, ABΑ is not calculated in the final estimation. In cases of ‘grey’ background, mammograms' contrast changed until to achieve an ABΑ background. Hence, only mammograms with correct contrast included in the final results. This method assured the correct density comparison among mammograms because the same scale of contrast was used to all mammograms and the breast itself had the correct mammographic ‘density’. Equally, with this method, no further calculations were necessary to compare breast densities among mammograms or the use of special tables, and the ‘automated’ percentages corresponded to the real mammographic density of a particular breast. In relation to clinical impression, we found a significant correlation between ACR quartiles, clinically estimated, with this grey scale percentage method. However, a significant percentage of clinical estimations (18%) could be classified as ‘not accurate’ with a discrepancy more than 20% of the ‘exact’ percentage of breast density. In particular, 7 mammogram densities were over– or subestimated (> 20 to 27% or > –20 to –25%). Mammographic screening usually involves the performance of the mediolateraloblique and craniocaudal projections. In a previous publication of our research team, due to the square shape of the aperture area examined with a Mac utility, MPM was not possible to be avoided without lose a part of breast tissue in mediolateraloblique projections. On the contrary, with this specially constructed program, the MPM was removed in all mediolateraloblique mammograms and this area was not calculated in the final estimation of breast density.Subjective fibroglandular density description could be a useful tool of breast cancer risk estimation in a particular woman. However, some degree of hesitation could arise when such a description belongs to MPD with increased risk of breast cancer. On the contrary, our method has ‘descriptive accuracy’. The method could be proposed as an objective tool of breast density measurement, a comparative tool between mammograms of the same woman in different periods with different stimulating factors of mammary proliferation and as comparative tool among mammograms of different women, subgrouping them in age groups, treatment groups etc. Similarly, previous studies, using a variety of methods, quantified objectively the MPD, correlate it with breast cancer risk and made digitized assessments of mammographic breast density in patients receiving hormonal regimens , 14, 15.Taking into account that breast density is actively related to breast cancer risk, methods of breast densitometry must be accurate, reliable, easy to learn, easy to perform, widely available, quick, cheap and repeatable. We believe that this method consists an essential improvement of our previous one regarding to accuracy and estimation of breast density in the exact ‘shape’ of a particular breast.