CBI’s Risk-based Monitoring Meeting – Philadelphia November 3-4, 2016

 

Please join us on November 3-4, 2016 at CBI’s RBM 2016 being held in Philadelphia at the Doubletree by Hilton Center City. At a session entitled “Leverage Real-Time Trial Data to Optimize Process and System Interoperability,“ Dr. Jules Mitchel, President of Target Health Inc., will share Target Health’s extensive clinical trials experience using eSource and Risk-Based Monitoring, including one FDA approval, as well as the results of regulatory inspections of Target Health and 8 clinical sites. The title of his presentation is “Learn to Monitor Clinical Trials with Real-Time Data.

 

The Isle of Dreams

 

On Friday, Glen Park and Jules Mitchel visited a client in Jersey City. Not only is the project really interesting, but we had a spectacular view of lower Manhattan. Photo shot by Jules Mitchel with iPhone6.

 

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Isle of Dreams – Foggy Day in the Big Apple  ©Target Health Inc.

 

For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website, and if you like the weekly newsletter, ON TARGET, you’ll love the Blog.

 

Joyce Hays, Founder and Editor in Chief of On Target

Jules Mitchel, Editor

 

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‘Sixth Sense’ May be More Than Just a Feeling

20161003-15

Early parapsychological research employed the use of Zener cards in experiments designed to test for the existence of telepathic communication, or clairvoyant or precognitive perception. Source: Wikipedia Commons

 

The sixth sense is another term for extrasensory 1) ___. Extrasensory perception (ESP) would involve the reception of information not gained through the recognized senses and not internally originated. The expression “sixth sense“ is a misnomer that falsely suggests that there is only one additional sense besides the traditional five senses of sight, hearing, touch, smell, and taste, a classification attributed to Aristotle. Humans have at least five additional senses that include: nociception (pain); equilibrioception (balance); proprioception and kinaesthesia (joint motion and acceleration); sense of time; thermoception (temperature differences); and possibly an additional weak magnetoception(direction). There is no firm agreement among neurologists as to the number of senses because of differing definitions of what constitutes a 2) ___. The senses and their operation, classification, and theory are overlapping topics studied by a variety of fields, most notably Neuroscience, cognitive psychology, and philosophy of perception. The nervous system has a specific sensory system, or organ, that manages each sense. One categorization for human senses is as follows: chemoreception; photoreception; mechanoreception; and thermoception. This categorization has been criticized as too restrictive, however, as it does not include categories for accepted senses such as the sense of time and sense of pain. Some non-human animals possess senses that are absent in humans, such as electroreception and detection of polarized light.

 

Study of rare genetic disorder reveals importance of touch and body awareness. With the help of two young patients with a unique neurological disorder, scientists have discovered that a 3) ___ called PIEZO2 controls specific aspects of human touch and proprioception, a “sixth sense“ describing awareness of one’s body in space. Mutations in the gene caused the two to have movement and balance problems and the loss of some forms of touch. Despite their difficulties, they both appeared to cope with these challenges by relying heavily on vision and other senses.

 

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Unlocking the mysteries of our senses: An NIH Study shows that two young patients with a mutation in the PIEZO2 have problems with touch and proprioception, or body awareness. Credit: Bonnemann Lab, NIH/NINDS, Bethesda, MD

 

“Our study highlights the critical importance of PIEZO2 and the senses it controls in our daily lives,“ said Carsten G. Bonnemann, M.D., senior investigator at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and a co-leader of the study published in the New England Journal of Medicine. “The results establish that PIEZO2 is a touch and proprioception gene in 4) ___. Understanding its role in these senses may provide clues to a variety of neurological disorders.“ Dr. Bonnemann’s team uses cutting edge genetic techniques to help diagnose children around the world who have disorders that are difficult to characterize. The two patients in this study are unrelated, one nine and the other 19 years old. They have difficulties walking; hip, finger and foot deformities; and abnormally curved 5) ___ diagnosed as progressive scoliosis. Working with the laboratory of Alexander T. Chesler, Ph.D., investigator at NIH’s National Center for Complementary and Integrative Health (NCCIH), the researchers discovered that the patients have mutations in the PIEZO2 gene that appear to block the normal production or activity of Piezo2 proteins in their cells. Piezo2 is what scientists call a mechanosensitive protein because it generates electrical 6) ___ signals in response to changes in cell shape, such as when skin cells and neurons of the hand are pressed against a table. Studies in mice suggest that Piezo2 is found in the neurons that control touch and proprioception. “As someone who studies Piezo2 in mice, working with these patients was humbling,“ said Dr. Chesler. “Our results suggest they are touch-blind. The patient’s version of Piezo2 may not work, so their neurons cannot detect touch or limb movements.“ Further examinations at the NIH Clinical Center suggested the young patients lack body awareness. Blindfolding them made walking extremely difficult, causing them to stagger and stumble from side to side while assistants prevented them from falling. When the researchers compared the two patients with unaffected volunteers, they found that blindfolding the young patients made it harder for them to reliably reach for an object in front of their faces than it was for the volunteers. Without looking, the patients could not guess the direction their joints were being moved as well as the control subjects could. The patients were also less sensitive to certain forms of touch. They could not feel vibrations from a buzzing tuning 7) ___ as well as the control subjects could. Nor could they tell the difference between one or two small ends of a caliper pressed firmly against their palms. Brain scans of one patient showed no response when the palm of her hand was brushed. Nevertheless, the patients could feel other forms of touch. Stroking or brushing hairy skin is normally perceived as pleasant. Although they both felt the brushing of hairy skin, one claimed it felt prickly instead of the pleasant sensation reported by unaffected volunteers. 8) ___ scans showed different activity patterns in response to brushing between unaffected volunteers and the patient who felt prickliness. Despite these differences, the patients’ nervous systems appeared to be developing normally. They were able to feel pain, itch, and temperature normally; the nerves in their limbs conducted electricity rapidly; and their brains and cognitive abilities were similar to the control subjects of their age. “What’s remarkable about these patients is how much their nervous systems compensate for their lack of touch and body awareness,“ said Dr. Bonnemann. “It suggests the nervous system may have several alternate pathways that we can tap into when designing new therapies.“

 

Previous studies found that mutations in PIEZO2 may have various effects on the Piezo2 protein that may result in genetic musculoskeletal disorders, including distal arthrogryposis type 5, Gordon Syndrome, and Marden-Walker Syndrome. Drs. Bonnemann and Chesler concluded that the scoliosis and joint problems of the patients in this study suggest that Piezo2 is either directly required for the normal growth and alignment of the skeletal system or that touch and proprioception indirectly guide 9) ___ development. “Our study demonstrates that bench and bedside research are connected by a two-way street,“ said Dr. Chesler. “Results from basic laboratory research guided our examination of the children. Now we can take that knowledge back to the lab and use it to design future experiments investigating the role of PIEZO2 in nervous 10) ___ and musculoskeletal development.“ This work was supported by the NCCIH and NINDS intramural research programs.

 

Sources: National Institutes of Health; Journal ReferenceThe Role of PIEZO2 in Human MechanosensationNew England Journal of Medicine, 2016; DOI:10.1056/NEJMoa1602812; ScienceDaily

 

ANSWERS: 1) perception; 2) sense; 3) gene; 4) humans; 5) spines; 6) nerve; 7) fork; 8) Brain; 9) skeletal; 10) system

 

John Locke, Philosopher and Physician

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Portrait of John Locke, by Godfrey Kneller, National Portrait Gallery, London

 

 

Editor’s note: We’re including, in History of Medicine, the well-known philosopher, John Locke, in this edition of the newsletter, because we didn’t realize (and readers might like to know), that this great thinker was also a physician.

 

John Locke FRS (1632-1704) was an English philosopher and physician, widely regarded as one of the most influential of Enlightenment thinkers and commonly known as the “Father of Liberalism“. Considered one of the first of the British empiricists, following the tradition of Sir Francis Bacon, he is equally important to social contract theory. His work greatly affected the development of epistemology and political philosophy. His writings influenced Voltaire and Rousseau, many Scottish Enlightenment thinkers, as well as the American revolutionaries. His contributions to classical republicanism and liberal theory are reflected in the United States Declaration of Independence. Locke’s theory of mind is often cited as the origin of modern conceptions of identity and the self, figuring prominently in the work of later philosophers such as Hume, Rousseau, and Kant. Locke was the first to define the self through a continuity of consciousness. He postulated that, at birth, the mind was a blank slate or tabula rasa. Contrary to Cartesian philosophy based on pre-existing concepts, he maintained that we are born without innate ideas, and that knowledge is instead determined only by experience derived from sense perception.

 

Locke was born on 29 August 1632, in a small thatched cottage by the church in Wrington, Somerset, about 12 miles from Bristol. He was baptized the same day. Soon after Locke’s birth, the family moved to the market town of Pensford, about seven miles south of Bristol, where Locke grew up in a rural Tudor house in Belluton. Locke’s father, also called John, was a country lawyer and clerk to the Justices of the Peace in Chew Magna, who had served as a captain of cavalry for the Parliamentarian forces during the early part of the English Civil War. His mother was Agnes Keene. Both parents were Puritans. In 1647, Locke was sent to the prestigious Westminster School in London under the sponsorship of Alexander Popham, a member of Parliament and his father’s former commander. After completing studies there, he was admitted to Christ Church, Oxford, in the autumn of 1652 at the age of twenty. The dean of the college at the time was John Owen, vice-chancellor of the university. Although a capable student, Locke was irritated by the undergraduate curriculum of the time. He found the works of modern philosophers, such as Rene Descartes, more interesting than the classical material taught at the university. Through his friend Richard Lower, whom he knew from the Westminster School, Locke was introduced to medicine and the experimental philosophy being pursued at other universities and in the Royal Society, of which he eventually became a member. Locke was awarded a bachelor’s degree in February 1656 and a master’s degree in June 1658. He obtained a bachelor of medicine in February 1675, having studied medicine extensively during his time at Oxford and worked with such noted scientists and thinkers as Robert Boyle, Thomas Willis, Robert Hooke and Richard Lower. In 1666, he met Lord Anthony Ashley Cooper, 1st Earl of Shaftesbury, who had come to Oxford seeking treatment for a liver infection. Cooper was impressed with Locke and persuaded him to become part of his retinue.

 

Locke had been looking for a career and in 1667 moved into Shaftesbury’s home at Exeter House in London, to serve as Lord Ashley’s personal physician. In London, Locke resumed his medical studies under the tutelage of Thomas Sydenham. Sydenham had a major effect on Locke’s natural philosophical thinking – an effect that would become evident in An Essay Concerning Human Understanding. Locke’s medical knowledge was put to the test when Shaftesbury’s liver infection became life-threatening. Locke coordinated the advice of several physicians and was probably instrumental in persuading Shaftesbury to undergo surgery (then life-threatening itself) to remove the cyst. Shaftesbury survived and prospered, crediting Locke with saving his life. During this time, Locke served as Secretary of the Board of Trade and Plantations and Secretary to the Lords Proprietor of Carolina, which helped to shape his ideas on international trade and economics.

 

Shaftesbury, as a founder of the Whig movement, exerted great influence on Locke’s political ideas. Locke became involved in politics when Shaftesbury became Lord Chancellor in 1672. Following Shaftesbury’s fall from favor in 1675, Locke spent some time travelling across France as tutor and medical attendant to Caleb Banks. He returned to England in 1679 when Shaftesbury’s political fortunes took a brief positive turn. Around this time, most likely at Shaftesbury’s prompting, Locke composed the bulk of the Two Treatises of Government. While it was once thought that Locke wrote the Treatises to defend the Glorious Revolution of 1688, recent scholarship has shown that the work was composed well before this date. The work is now viewed as a more general argument against absolute monarchy (particularly as espoused by Robert Filmer and Thomas Hobbes) and for individual consent as the basis of political legitimacy. Although Locke was associated with the influential Whigs, his ideas about natural rights and government are today considered quite revolutionary for that period in English history.

 

Locke fled to the Netherlands in 1683, under strong suspicion of involvement in the Rye House Plot, although there is little evidence to suggest that he was directly involved in the scheme. The philosopher and novelist Rebecca Newberger Goldstein argues that during his five years in Holland, Locke chose his friends “from among the same freethinking members of dissenting Protestant groups as Spinoza’s small group of loyal confidants. Locke almost certainly met men in Amsterdam who spoke of the ideas of that renegade Jew who insisted on identifying himself through his religion of reason alone.“ While she says that “Locke’s strong empiricist tendencies“ would have “disinclined him to read a grandly metaphysical work such as Spinoza’s Ethics, in other ways he was deeply receptive to Spinoza’s ideas, most particularly to the rationalist’s well thought out argument for political and religious tolerance and the necessity of the separation of church and state.“ In the Netherlands, Locke had time to return to his writing, spending a great deal of time re-working the Essay and composing the Letter on Toleration. Locke did not return home until after the Glorious Revolution. Locke accompanied William of Orange’s wife back to England in 1688. The bulk of Locke’s publishing took place upon his return from exile – his aforementioned Essay Concerning Human Understanding, the Two Treatises of Civil Government and A Letter Concerning Toleration all appearing in quick succession.

 

Locke’s close friend Lady Masham invited him to join her at the Mashams’ country house in Essex. Although his time there was marked by variable health from asthma attacks, he nevertheless became an intellectual hero of the Whigs. During this period he discussed matters with such figures as John Dryden and Isaac Newton. Locke died on 28 October 1704, and is buried in the churchyard of the village of High Laver, east of Harlow in Essex, where he had lived in the household of Sir Francis Masham since 1691. Locke never married nor had children.

Events that happened during Locke’s lifetime include the English Restoration, the Great Plague of London and the Great Fire of London. He did not quite see the Act of Union of 1707, though the thrones of England and Scotland were held in personal union throughout his lifetime. Constitutional monarchy and parliamentary democracy were in their infancy during Locke’s time.

 

Influence

 

In the late 17th and early 18th centuries, Locke’s Two Treatises were rarely cited. Historian Julian Hoppit said of the book, “except among some Whigs, even as a contribution to the intense debate of the 1690s it made little impression and was generally ignored until 1703 (though in Oxford in 1695 it was reported to have made ‘a great noise’)“. John Kenyon, in his study of British political debate from 1689 to 1720, has remarked that Locke’s theories were “mentioned so rarely in the early stages of the [Glorious] Revolution, up to 1692, and even less thereafter, unless it was to heap abuse on them“ and that “no one, including most Whigs, [were] ready for the idea of a notional or abstract contract of the kind adumbrated by Locke“. In contrast, Kenyon adds that Algernon Sidney’s Discourses Concerning Government were “certainly much more influential than Locke’s Two Treatises“. In the 50 years after Queen Anne’s death in 1714, the Two Treatises were reprinted only once (except in the collected works of Locke). However, with the rise of American resistance to British taxation, the Second Treatise gained a new readership; it was frequently cited in the debates in both America and Britain. The first American printing occurred in 1773 in Boston.

 

Locke exercised a profound influence on political philosophy, in particular on modern liberalism. Michael Zuckert has argued that Locke launched liberalism by tempering Hobbesian absolutism and clearly separating the realms of Church and State. He had a strong influence on Voltaire who called him “le sage Locke“. His arguments concerning liberty and the social contract later influenced the written works of Alexander Hamilton, James Madison, Thomas Jefferson, and other Founding Fathers of the United States. In fact, one passage from the Second Treatise is reproduced verbatim in the Declaration of Independence, the reference to a “long train of abuses“. Such was Locke’s influence that Thomas Jefferson wrote: “Bacon, Locke and Newton – I consider them as the three greatest men that have ever lived, without any exception, and as having laid the foundation of those superstructures which have been raised in the Physical and Moral sciences“. But Locke’s influence may have been even more profound in the realm of epistemology. Locke redefined subjectivity, or self, and intellectual historians such as Charles Taylor and Jerrold Seigel argue that Locke’s An Essay Concerning Human Understanding (1690) marks the beginning of the modern Western conception of the self. Locke, writing his Letters Concerning Toleration (1689-92) in the aftermath of the European wars of religion, formulated a classic reasoning for religious tolerance. Three arguments are central: (1) Earthly judges, the state in particular, and human beings generally, cannot dependably evaluate the truth-claims of competing religious standpoints; (2) Even if they could, enforcing a single “true religion“ would not have the desired effect, because belief cannot be compelled by violence; (3) Coercing religious uniformity would lead to more social disorder than allowing diversity. With regard to his position on religious tolerance, Locke was influenced by Baptist theologians like John Smyth and Thomas Helwys, who had published tracts demanding freedom of conscience in the early 17th century. Baptist theologian Roger Williams founded the colony Rhode Island in 1636, where he combined a democratic constitution with unlimited religious freedom. His tract The Bloody Tenent of Persecution for Cause of Conscience (1644), which was widely read in the mother country, was a passionate plea for absolute religious freedom and the total separation of church and state. Freedom of conscience had had high priority on the theological, philosophical and political agenda, since Martin Luther refused to recant his beliefs before the Diet of the Holy Roman Empire at Worms in 1521, unless he would be proved false by the Bible.

 

Appraisals of Locke have often been tied to appraisals of liberalism in general, and to appraisals of the United States. Detractors note that in 1671 he was a major investor in the English slave-trade through the Royal African Company. In addition, he participated in drafting the Fundamental Constitutions of Carolina while Shaftesbury’s secretary, which established a feudal aristocracy and gave a master absolute power over his slaves. For example, Martin Cohen notes that Locke, as a secretary to the Council of Trade and Plantations (1673-4) and a member of the Board of Trade (1696-1700), was in fact, “one of just half a dozen men who created and supervised both the colonies and their iniquitous systems of servitude“. Some see his statements on unenclosed property as having been intended to justify the displacement of the Native Americans. Because of his opposition to aristocracy and slavery in his major writings, he is accused of hypocrisy and racism, or of caring only for the liberty of English capitalists. Locke also drafted implementing instructions for the Carolina colonists designed to ensure that settlement and development was consistent with the Fundamental Constitutions. Collectively, these documents are known as the Grand Model for the Province of Carolina. Locke uses the word property in both broad and narrow senses. In a broad sense, it covers a wide range of human interests and aspirations; more narrowly, it refers to material goods. He argues that property is a natural right and it is derived from labor. In Chapter V of his Second Treatise, Locke argues that the individual ownership of goods and property is justified by the labor exerted to produce those goods or utilize property to produce goods beneficial to human society. Locke stated his belief, in his Second Treatise, that nature on its own provides little of value to society, implying that the labor expended in the creation of goods gives them their value. This position can be seen as a labor theory of value. From this premise, Locke developed a labor theory of property, namely that ownership of property is created by the application of labor. In addition, he believed that property precedes government and government cannot “dispose of the estates of the subjects arbitrarily.“ Karl Marx later critiqued Locke’s theory of property in his own social theory.

 

Locke’s political theory was founded on social contract theory. Unlike Thomas Hobbes, Locke believed that human nature is characterized by reason and tolerance. Like Hobbes, Locke believed that human nature allowed people to be selfish. This is apparent with the introduction of currency. In a natural state all people were equal and independent, and everyone had a natural right to defend his “Life, health, Liberty, or Possessions.“ Most scholars trace the phrase “life, liberty, and the pursuit of happiness,“ in the American Declaration of Independence, to Locke’s theory of rights, though other origins have been suggested. Like Hobbes, Locke assumed that the sole right to defend in the state of nature was not enough, so people established a civil society to resolve conflicts in a civil way with help from government in a state of society. However, Locke never refers to Hobbes by name and may instead have been responding to other writers of the day. Locke also advocated governmental separation of powers and believed that revolution is not only a right but an obligation in some circumstances. These ideas would come to have profound influence on the Declaration of Independence and the Constitution of the United States. According to Locke, unused property is wasteful and an offence against nature, but, with the introduction of “durable“ goods, men could exchange their excessive perishable goods for goods that would last longer and thus not offend the natural law. In his view, the introduction of money marks the culmination of this process, making possible the unlimited accumulation of property without causing waste through spoilage. He also includes gold or silver as money because they may be “hoarded up without injury to anyone,“ since they do not spoil or decay in the hands of the possessor. In his view, the introduction of money eliminates the limits of accumulation. Locke stresses that inequality has come about by tacit agreement on the use of money, not by the social contract establishing civil society or the law of land regulating property. Locke is aware of a problem posed by unlimited accumulation but does not consider it his task. He just implies that government would function to moderate the conflict between the unlimited accumulation of property and a more nearly equal distribution of wealth; he does not identify which principles that government should apply to solve this problem. However, not all elements of his thought form a consistent whole. For example, labor theory of value of the Two Treatises of Government stands side by side with the demand-and-supply theory developed in a letter he wrote titled Some Considerations on the Consequences of the Lowering of Interest and the Raising of the Value of Money. Moreover, Locke anchors property in labor but in the end upholds the unlimited accumulation of wealth.

 

Locke’s general theory of value and price is a supply and demand theory, which was set out in a letter to a Member of Parliament in 1691, titled Some Considerations on the Consequences of the Lowering of Interest and the Raising of the Value of Money. He refers to supply as “quantity“ and demand as “rent“. “The price of any commodity rises or falls by the proportion of the number of buyer and sellers,“ and “that which regulates the price… [of goods] is nothing else but their quantity in proportion to their rent.“ The quantity theory of money forms a special case of this general theory. His idea is based on “money answers all things“ (Ecclesiastes) or “rent of money is always sufficient, or more than enough,“ and “varies very little.“ Locke concludes that as far as money is concerned, the demand is exclusively regulated by its quantity, regardless of whether the demand for money is unlimited or constant. He also investigates the determinants of demand and supply. For supply, he explains the value of goods as based on their scarcity and ability to be exchanged and consumed. He explains demand for goods as based on their ability to yield a flow of income. Locke develops an early theory of capitalization, such as land, which has value because “by its constant production of saleable commodities it brings in a certain yearly income.“ He considers the demand for money as almost the same as demand for goods or land; it depends on whether money is wanted as medium of exchange. As a medium of exchange, he states that “money is capable by exchange to procure us the necessaries or conveniences of life,“ and for loanable funds, “it comes to be of the same nature with land by yielding a certain yearly income or interest.“ Locke distinguishes two functions of money, as a “counter“ to measure value, and as a “pledge“ to lay claim to goods. He believes that silver and gold, as opposed to paper money, are the appropriate currency for international transactions. Silver and gold, he says, are treated to have equal value by all of humanity and can thus be treated as a pledge by anyone, while the value of paper money is only valid under the government which issues it.

 

Locke argues that a country should seek a favorable balance of trade, lest it fall behind other countries and suffer a loss in its trade. Since the world money stock grows constantly, a country must constantly seek to enlarge its own stock. Locke develops his theory of foreign exchanges, in addition to commodity movements, there are also movements in country stock of money, and movements of capital determine exchange rates. He considers the latter less significant and less volatile than commodity movements. As for a country’s money stock, if it is large relative to that of other countries, he says it will cause the country’s exchange to rise above par, as an export balance would do. He also prepares estimates of the cash requirements for different economic groups (landholders, laborers and brokers). In each group he posits that the cash requirements are closely related to the length of the pay period. He argues the brokers – middlemen – whose activities enlarge the monetary circuit and whose profits eat into the earnings of laborers and landholders, have a negative influence on both personal and the public economy to which they supposedly contribute. Locke defines the self as “that conscious thinking thing, (whatever substance, made up of whether spiritual, or material, simple, or compounded, it matters not) which is sensible, or conscious of pleasure and pain, capable of happiness or misery, and so is concerned for itself, as far as that consciousness extends“. He does not, however, ignore “substance“, writing that “the body too goes to the making the man.“

 

In his Essay, Locke explains the gradual unfolding of this conscious mind. Arguing against both the Augustinian view of man as originally sinful and the Cartesian position, which holds that man innately knows basic logical propositions, Locke posits an “empty“ mind, a tabula rasa, which is shaped by experience; sensations and reflections being the two sources of all our ideas. Locke’s Some Thoughts Concerning Education is an outline on how to educate this mind: he expresses the belief that education maketh the man, or, more fundamentally, that the mind is an “empty cabinet“, with the statement, “I think I may say that of all the men we meet with, nine parts of ten are what they are, good or evil, useful or not, by their education.“ Locke also wrote that “the little and almost insensible impressions on our tender infancies have very important and lasting consequences.“ He argued that the “associations of ideas“ that one makes when young are more important than those made later because they are the foundation of the self: they are, put differently, what first mark the tabula rasa. In his Essay, in which both these concepts are introduced, Locke warns against, for example, letting “a foolish maid“ convince a child that “goblins and sprites“ are associated with the night for “darkness shall ever afterwards bring with it those frightful ideas, and they shall be so joined, that he can no more bear the one than the other.“ This theory came to be called “associationism“, and it strongly influenced 18th-century thought, particularly educational theory, as nearly every educational writer warned parents not to allow their children to develop negative associations. It also led to the development of psychology and other new disciplines with David Hartley’s attempt to discover a biological mechanism for associationism in his Observations on Man (1749).

 

Drug to Treat Alcoholism Shows Promise

 

According to a study published online in the journal Neuropsychopharmacology (September 2016), a new medication that targets part of the brain’s stress system may help reduce alcohol use in people with alcohol use disorder (AUD). The investigation was a 12-week, randomized clinical trial that recruited 144 alcohol-dependent adult men and women. The investigational product, called ABT-436, was designed to block the effects of vasopressin, a neuropeptide produced in the hypothalamus of the brain. Vasopressin helps to regulate the pituitary adrenal axis and other brain circuits involved in emotion. As a result, it plays a role in regulating stress, anxiety, and their interaction with AUD.”

 

During the 28-day baseline period, female participants consumed at least 28 drinks per week, while male participants consumed at least 35 drinks per week. Participants were then randomized to receive either placebo tablets or ones containing ABT-436. During the study participants’ alcohol consumption was monitored, as well as their mood changes and smoking habits, as these are known to co-vary with alcohol consumption.

 

Results showed that participants receiving ABT-436 experienced more days of alcohol abstinence than those receiving the placebo. In particular, participants who reported high levels of stress appeared to respond better to ABT-436, in that both the frequency of their drinking and the number of heavy drinking days they experienced decreased. The authors suggested that potential future studies with drugs targeting vasopressin blockade should focus on populations of people with AUD who also report high levels of stress. Smokers may be another population that could benefit from ABT-436. In addition to its effects on alcohol consumption, study participants receiving the ABT-436 experienced a reduction in smoking. The authors suspected that ABT-436 might be targeting the same areas in the brain that relate to withdrawal and stress, and, in the process, influencing both tobacco and alcohol use disorders. Additional research is needed to determine if that is the case.

 

Morning Sickness Linked to Lower Risk of Pregnancy Loss

 

Nausea and vomiting that occurs in pregnancy is often called “morning sickness,“ as these symptoms typically begin in the morning and usually resolve as the day progresses. For most women, nausea and vomiting subside by the 4th month of pregnancy. Others may have these symptoms for the duration of their pregnancies. The cause of morning sickness is not known, but researchers have proposed that it protects the fetus against toxins and disease-causing organisms in foods and beverages.

 

It’s a common thought that nausea indicates a healthy pregnancy, but there wasn’t a lot of high-quality evidence to support this belief. As a result, a study published online in JAMA Internal Medicine (26 September 2016), was performed to evaluate symptoms from the earliest weeks of pregnancy, immediately after conception, and to assess whether there is a protective association between nausea and vomiting and a lower risk of pregnancy loss.

 

For the analysis, data from all the women in a study who had a positive pregnancy test, were evaluated from the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial. This trial tested whether taking daily low-dose aspirin prevents women who experienced one or two prior pregnancy losses from experiencing a future loss. The women kept daily diaries of whether they experienced nausea and vomiting in the 2nd through the 8th week of their pregnancies and then responded to a monthly questionnaire on their symptoms through the 36th week of pregnancy. The study authors noted that most previous studies on nausea and pregnancy loss were not able to obtain such detailed information on symptoms in these early weeks of pregnancy. Instead, most of studies had relied on the women’s recollection of symptoms much later in pregnancy or after they had experienced a pregnancy loss.

 

In the EAGeR trial, a total of 797 women had positive pregnancy tests, with 188 pregnancies ending in loss. By the 8th week of pregnancy, 57.3% of the women reported experiencing nausea and 26.6% reported nausea with vomiting. Results showed that these women were 50 to 75% less likely to experience a pregnancy loss, compared to those who had not experienced nausea alone or nausea accompanied by vomiting.

 

According to the authors, among women with 1 or 2 prior pregnancy losses, nausea and vomiting were common very early in pregnancy and were associated with a reduced risk for pregnancy loss. The authors added that the findings overcome prior analytic and design limitations and represent the most definitive data available to date indicating the protective association of nausea and vomiting in early pregnancy and the risk for pregnancy loss.

 

First Automated Insulin Delivery Device for Type 1 Diabetes Approved

 

The human pancreas naturally supplies a low, continuous rate of insulin, known as basal or background insulin. In patients with diabetes, the body’s ability to produce or respond to insulin is impaired.

 

According to the U. S. Centers for Disease Control and Prevention, approximately 5% of people with diabetes have type 1 diabetes. Also known as juvenile diabetes, type 1 diabetes is typically diagnosed in children and young adults. Because the pancreas does not make insulin in people with type 1 diabetes, patients have to consistently monitor their glucose levels throughout the day and have insulin therapy through injection with a syringe, an insulin pen or insulin pump to avoid becoming hyperglycemic (high glucose levels). In addition, management of type 1 diabetes includes following a healthy eating plan and physical activity.

 

The FDA has approved Medtronic’s MiniMed 670G hybrid closed looped system, the first FDA-approved device that is intended to automatically monitor glucose (sugar) and provide appropriate basal insulin doses in people 14 years of age and older with type 1 diabetes. The MiniMed 670G hybrid closed looped system, often referred to as an “artificial pancreas,“ is intended to adjust insulin levels with little or no input from the user. It works by measuring glucose levels every five minutes and automatically administering or withholding insulin. The system includes a sensor that attaches to the body to measure glucose levels under the skin; an insulin pump strapped to the body; and an infusion patch connected to the pump with a catheter that delivers insulin. While the device automatically adjusts insulin levels, users need to manually request insulin doses to counter carbohydrate (meal) consumption.

 

The FDA evaluated data from a clinical trial of the MiniMed 670G hybrid closed looped system that included 123 participants with type 1 diabetes. The clinical trial included an initial two-week period where the system’s hybrid closed loop was not used followed by a three-month study during which trial participants used the system’s hybrid closed loop feature as frequently as possible. This clinical trial showed that the device is safe for use in people 14 years of age and older with type 1 diabetes. No serious adverse events, diabetic ketoacidosis (DKA) or severe hypoglycemia (low glucose levels) were reported during the study. Risks associated with use of the system may include hypoglycemia, hyperglycemia, as well as skin irritation or redness around the device’s infusion patch. This version of this device is unsafe for use in children 6 years of age or younger and in patients who require less than eight units of insulin per day.

 

As part of this approval, the FDA is requiring a post-market study to better understand how the device performs in real-world settings. While the device is being approved today for use in people 14 years of age and older with type 1 diabetes, Medtronic is currently performing clinical studies to evaluate the safety and effectiveness of the device in diabetic children 7-13 years old.

 

The MiniMed 670G hybrid closed looped system is manufactured by Medtronic, headquartered in Dublin, Ireland.

 

Oregano Corn-Potatoes with Ginger and Garlic

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I’m still on my locally harvested corn shtick; I can’t help it, the corn is so sweet and delicious this year. I keep looking

for new, tasty ways to serve it and out of that, comes a new recipe. ©Joyce Hays, Target Health Inc.

 

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We are becoming magnetized to beautiful veggies. ©Joyce Hays, Target Health Inc.

 

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We had the corn/potato recipe with my other recipe for kale/mushroom burgers.

©Joyce Hays, Target Health Inc.

 

 

Ingredients

 

2 pounds red potatoes, scrubbed and chopped (keep skins on)

20 fresh garlic cloves, sliced but not thin slices (roast with potatoes)

10+ fresh garlic cloves, cooked with corn

4 teaspoons fresh oregano, well chopped (for potatoes)

4 teaspoons fresh oregano, well chopped (for corn mixture)

4 teaspoon fresh cilantro, well chopped (for corn mixture)

Pinch salt

Pinch black pepper

Pinch chili flakes

1 Tablespoon ginger puree

1 Tablespoon lemongrass paste

1 teaspoon turmeric

1/2 teaspoon ground coriander

1 teaspoon cardamom

6 fresh ears corn, all kernels scraped off

1 teaspoon kosher salt for steaming

Olive oil for cooking

 

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Simple, healthy, tasty and easy to make. ©Joyce Hays, Target Health Inc.

 

 

Directions

 

1. Preheat oven to 375 degrees

2. Chop everything that needs chopping and shuck the corn.

3. Scrub the potatoes, then slice and cut into small pieces.

4. Slice the 20 fresh garlic cloves into large slices. Slice the other 10 garlic cloves into thinner slices.

5. Put potatoes in one layer, on an oiled baking sheet. Sprinkle the sliced 20 garlic cloves over the potatoes, sprinkle 4 teaspoons oregano over the potatoes. Glug extra virgin olive oil over the potatoes and roast in 375 oven for 30 to 40 minutes, or until the pieces are light brown and crispy around the edges. Remove when done and set aside,

 

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Chopping garlic and herbs all on same board and at the same time.

©Joyce Hays, Target Health Inc.

 

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Scrub potatoes, then cut into small pieces and put on a baking tray.

©Joyce Hays, Target Health Inc.

 

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Before you roast the potatoes, glug extra virgin olive oil over them, add the 20 garlic cloves (large slices), and sprinkle 4 teaspoons of fresh oregano over the potatoes. Put in oven to roast, until they start to get light brown and crispy. ©Joyce Hays, Target Health Inc.

 

 

6. While potatoes are roasting, cook the other 10 garlic cloves in extra virgin olive oil, until both sides of the garlic are light brown.

 

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Scrape all corn off the cobs and put into a bowl. Add all spices and herbs to this bowl, but not the 10+ garlic cloves. ©Joyce Hays, Target Health Inc.

 

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Mix together all the herbs and spices with the fresh corn kernels. ©Joyce Hays, Target Health Inc.

 

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Cook the 10+ garlic cloves (thick slices of garlic). Stir constantly until both sides of the garlic are light brown

©Joyce Hays, Target Health Inc.

 

7. Get out a medium bowl and add all the herbs and spices to the bowl, as well as the corn kernels, scraped off the fresh ears of corn. Set aside.

8. When the garlic is cooked, add the contents of the bowl of herbs, spices and corn, to the pan, stirring constantly. Cook for about 1/2 to 1 minute.

 

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After the garlic slices have gotten light brown, add the contents of the bowl with the corn mixture and stir. Cook about 1 or 1 and 1/2 minutes. You don’t want to overcook the corn. ©Joyce Hays, Target Health Inc.

 

 

9. When corn mixture is cooked, add the potatoes, just to warm them up, and mix everything together in the pan.

10. Finally, to serve, arrange everything, together, potatoes and corn/spice/herb mixture on a platter or serving bowl.

 

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We started out with crudites. ©Joyce Hays, Target Health Inc.

 

20161003-13

Another old favorite, chilled Pouilly Fuisse, went well with our whole meal, simple and tasty. We started with crudites and a low calorie dip, I threw together which turned out to be extremely good, plus warm sourdough rolls & extra virgin olive oil; next the recipe in this newsletter, Corn/potatoes with Kale/Mushroom Patties and an avocado topping for the patties; last our low calorie standby, strawberry jello cake. ©Joyce Hays, Target Health Inc.

 

We saw the Broadway show, Beautiful and loved it; dinner Italiano afterwards; a perfect day!

 

Carol King singing, You’ve Got a Friend

 

2015 White House Concert: Sara Bareilles, You’ve Got a Friend

 

From Our Table to Yours !

 

Bon Appetit!