Target Document® – Solution to the eTMF and Document Management


Target Document when used as an eTMF eliminates this mess


Target Document® is a secure, USER FRIENDLY, 21 CFR Part 11 compliant, web-based document distribution and management system which enables users, depending on their roles and responsibilities to post, share, electronically sign, and archive any electronic document, all within a web browser and without installing any software. Access to documents can also be timed to be viewed and/or expired, and there is a communication tool which allows for discussions about specific documents. Target Document® reduces the need to distribute documents via email and is ideal for companies wanting their own system to communicate with customers, vendors, employees, etc. It is also ideal for managing due diligence.




  1. Friendly user interface without any clutter or useless features
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  1. 21 CFR Part 11 Compliant
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  4. Login ID/password security (also used for sign-offs)
  5. User self-registration with department administrator approval
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ON TARGET is the newsletter of Target Health Inc., a NYC-based, full-service, contract research organization (eCRO), providing strategic planning, regulatory affairs, clinical research, data management, biostatistics, medical writing and software services to the pharmaceutical and device industries, including the paperless clinical trial.


For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). 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 HealthWebsite.


Joyce Hays, Founder and Editor in Chief of On Target

Jules Mitchel, Editor



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Lachrymose: The Importance of Being Lachrymose


Angel of Grief“ by William W. Story


The adjective “lachrymose“ comes from Latin “lacrimosus“ (from the noun “lacrima,“ meaning “tear“). “Lachrymose“ didn’t appear in English until around 1727, but another closely related adjective can be traced all the way back to the 15th century. This earlier cousin, “lachrymal“ (sometimes spelled “lacrimal,“ particularly in its scientific applications) is based in the realm of science rather than emotion. It is defined as “of, relating to, or being glands that produce 1) ___“ or “of, relating to, or marked by tears.“ On the other hand, “lachrymose“ is associated with the strong feelings that often cause those tears to flow, or something that produces those feelings.


Scientific research supports the accuracy of ancient folk wisdom that crying is good for our health. Although 2) ___ is a universal human experience that appears in every culture throughout history, we understand very little about this common yet mysterious phenomenon. Traumatic events, prolonged stress, loneliness, loss, pain, and simple daily hassles often trigger crying. Yet, most people have also cried tears of happiness, joy, and relief. How often and for what reasons people weep are influenced by many factors including gender, age, perceptions of events, societal attitudes, health, personality characteristics, and so on. Curiously, we have learned more about weeping from poetry, fiction, and movies than from medical and psychological studies. However, these scientific studies provide strong and consistent evidence that crying is linked to significant 3) ___ benefits.


Biomedical researchers have identified four biological mechanisms that function as catalysts influencing the amount of tears we will shed at a given time: genetic influences, dietary factors, hormone levels and circadian rhythms (we are more likely to cry if we are sleep 4) ___ and at certain times of day). Once the tear switch is flipped, a complex interplay of psychological and neurobiological processes allow tears to flow. We really know very little about the precise 5) ___ and biological processes that initiate an episode of crying or when it will stop. However, recent biological studies offer strong clues to how and why crying is related to health benefits. Commonly, people report they feel some sense of relief after a bout of crying. There is general agreement that there is a significant increase in the number, type and amount of stress hormones released in our bodies prior to crying. Consistently, researchers find that tears contain stress 6) ___. This is a critical finding since we know stress hormones cause damage to virtually all bodily systems.


During the last decade, stress hormones have been shown to cause serious damage to brain cells. Stress hormones seem to target specific parts of the brain including the hippocampus, hypothalamus, and pre-frontal 7) ___. Unfortunately, stress hormones attack the very brain sites implicated in the perpetuation of mood disorders. As a result, stress hormones damage the exact sites capable of reducing or eliminating the release of the toxic stress hormones. Finally, extensive biomedical studies demonstrate that stress hormones negatively affect virtually every system in the 8) ___ including the cardiovascular, gastrointestinal, endocrine, musculoskeletal, and immune systems. It is clear that crying is a primary way for the body to eliminate harmful stress hormones. Thus, crying is a natural and essential biological function that results in the elimination of 9) ___ hormones connected to every imaginable stress related health problem. The 21st century has started by removing any doubt about the positive health effects of crying.


Is it any wonder that people so often report feeling relieved after a good cry? From a public health perspective, it is obvious that the general public would benefit from a campaign to eliminate all stigma associated with crying so everyone can benefit from the innumerable positive health effects of crying. Practitioner’s of folk wisdom have routinely encouraged people to allow themselves to cry telling the suffering soul that “a good cry will help you feel better“. Some people report they rarely, if ever shed tears while others indicate crying is just a natural part of their lives. Those of us that have an aversion to crying would do well to toss out impediments to crying. Actually it takes courage to shed tears. Many men seem to “get it“ when informed that the refusal to cry when a wave of sadness comes, makes as much sense as refusing to eat when you feel 10) ___.


It is curious to watch scientists provide proof of things ordinary people have known for eons. Medical research has weighed in. We’ve been given “permission“ by scientists to allow a natural biological function to occur with knowledge that crying has many health benefits.


ANSWERS: 1) tears; 2) crying; 3) health; 4) deprived; 5) psychological; 6) hormones; 7) cortex; 8) body; 9) stress; 10) hungry


Wolfgang Amadeus Mozart (1756-1791)

Mozart c. 1780, detail from portrait (below) by Johann Nepomuk della Croce

The Mozart family on tour: Leopold, Wolfgang (would have been 7 when picture was painted), and Nannerl. Watercolor by Carmontelle, ca. 1763. The painting on the wall is of Wolfgang’s mother, who stayed in Salzburg on this tour.


Wolfgang Amadeus Mozart, prolific and influential composer of the Classical era, was one of the greatest and most beloved musical geniuses of all time. Mozart was born into a family with two well-educated and highly cultured parents, both of whom came from musical, scholarly families. If there is a creative musical gene, Wolfgang and his sister Nannerl inherited it. Authoritarian father, Leopold Mozart, intelligent and methodical, became a well-known Salzburg composer and teacher. The family lived well, as long as good financial manager, Leopold, watched the flow of expenditures. The youngest of seven children (five of whom died in infancy) Mozart (and Nannerl), well-schooled at home by his father, showed prodigious ability from his earliest childhood. Already competent on keyboard and violin, he composed from the age of five and performed before European royalty. When Mozart’s older sister, Nannerl was seven, she began keyboard lessons with her father while her three-year-old brother looked on. Years later, after her brother’s death, she reminisced:


He often spent much time at the clavier, picking out thirds, which he was ever striking, and his pleasure showed that it sounded good. In the fourth year of his age his father, for a game as it were, began to teach him a few minuets and pieces at the clavier. He could play it faultlessly and with the greatest delicacy, and keeping exactly in time. At the age of five, he was already composing little pieces, which he played to his father who wrote them down.


During Mozart’s youth, his family made quite a few European journeys in which he and Nannerl performed as child prodigies. These began with an exhibition, in 1762, at the court of the Prince-elector Maximilian III of Bavaria in Munich, and at the Imperial Court in Vienna and Prague. A long concert tour spanning three and a half years followed, taking the family to the courts of Munich, Mannheim, Paris, London, The Hague, again to Paris, and back home via Zurich, Donaueschingen, and Munich. These trips were often difficult and travel conditions were primitive. The family had to wait for invitations and reimbursement from the nobility and they endured long, near-fatal illnesses far from home: first Leopold with a throat infection (London, summer 1764) then both children with scarlet fever (The Hague, autumn 1765). In 1764, when Leopold was sick in London, and scheduled concerts had to be cancelled, Mozart spent the free time, composing his first symphony at the age of eight. On one trip, Mozart came down with small pox.


The Mozarts left London for the continent on 24 July 1765. Before this, Leopold allowed Wolfgang to be subjected to a scientific examination, conducted by The Hon. Daines Barrington. A report, issued in Philosophical Transactions for the year 1770, confirms the truth of Wolfgang’s exceptional capabilities. Practically the last act of the family in London was the gift to the British Museum of Wolfgang’s manuscript copy of “God is our Refuge“. Wolfgang was advertised as “the celebrated and astonishing Master Mozart, a Child of Seven Years of Age justly esteemed the most extraordinary Prodigy, and most amazing Genius, that has appeared in any Age“. During these trips, Mozart met a number of musicians and acquainted himself with the works of other composers. A particularly important influence was Johann Christian Bach, whom Mozart visited in London in 1764 and 1765. The family again went to Vienna in late 1767 and remained there, (apart from an enforced evacuation during a smallpox epidemic) until January 1769. These tours enabled the children to experience to the full the cosmopolitan musical world, and gave them an outstanding education. In Wolfgang’s case this would continue through further journeys. At 17, Wolfgang was engaged as a court musician in Salzburg, but grew restless and travelled in search of a better position, always composing abundantly. At 22, Mozart traveled to Paris with his beloved mother, where she became ill and died on July 3, 1778 of an undiagnosed illness. She was buried in the cemetery of Saint-Eustache. Heart broken, Wolfgang wrote the beautiful Sinfonia Concertante, K364, E-flat, for viola, violin and small orchestra, a musical form, popular in Paris at this time, that could be considered a requiem for his mother.


Wolfgang Amadeus Mozart Sinfonia Concertante K 364 in E flat major for Violin, Viola and Orchestra David & Igor Oistrakh, violin & viola Yehudi Menuhin conducts Moscow Philharmonic


While visiting Vienna in 1781, Mozart was dismissed from his Salzburg position and chose to stay in the capital, where he achieved fame but little financial security. During his final years in Vienna, he composed many of his best-known symphonies, concertos, and operas, and portions of the Requiem, which was largely unfinished at the time of his death. The circumstances of his early death have been much mythologized. He was survived by his wife Constanze and two sons.


Lacrimosa, from: Requiem de Mozart – Lacrimosa – Karl Bohm – Sinfonica de Viena


Mozart composed over 600 works, many acknowledged as pinnacles of symphonic, concertante, chamber, operatic, and choral music. He is among the most enduringly popular of classical composers, and his influence on subsequent Western art music is profound; Beethoven composed his own early works in the shadow of Mozart, and Joseph Haydn wrote that “posterity will not see such a talent again in 100 years.“ As it turned out, not in 223 years.


Mozart’s physical appearance was described by (his contemporary) tenor Michael Kelly, in his Reminiscences: “a remarkably small man, except for his large intense eyes. Very thin and pale, with a profusion of fine, fair hair of which he was rather vain. His facial complexion was pitted, a reminder of his childhood case of smallpox. He loved elegant clothing.“ Kelly remembered him at a rehearsal: “[He] was on the stage with his crimson pelisse and gold-laced cocked hat, giving the time of the music to the orchestra.“ Of his voice his wife later wrote that it “was a tenor, rather soft in speaking and delicate in singing, but when anything excited him, or it became necessary to exert it, it was both powerful and energetic“. Mozart usually worked long and hard, finishing compositions at a tremendous pace as deadlines approached. He often made sketches and drafts; unlike Beethoven’s these are mostly not preserved, as his wife sought to destroy them after his death. He was raised a Catholic and remained a loyal member of the Church throughout his life.


Mozart lived at the center of the Viennese musical world, and knew a great number and variety of people: fellow musicians, theatrical performers, fellow Salzburgers, and aristocrats, including some acquaintance with the Emperor Joseph II. His three closest friends appear to have been. Gottfried von Jacquin, Count August Hatzfeld, and Sigmund Barisani; others included his older colleague Joseph Haydn, singers Franz Xaver Gerl and Benedikt Schack, and the horn player Joseph Leutgeb. Leutgeb and Mozart carried on a curious kind of friendly mockery, often with Leutgeb as the butt of Mozart’s practical jokes. He enjoyed billiards and dancing, and kept pets: a canary, a starling, a dog, and a horse for recreational riding. He had a startling fondness for scatological humor, which is preserved in his surviving letters, notably those written to his cousin Maria Anna Thekla Mozart around 1777-1778, and in his correspondence with his sister and parents. Mozart also wrote scatological music, a series of canons that he sang with his friends.


Reproduction of the original manuscript of Mozart’s canon “Difficile Lectu“. The words “lectu mihi mars“ were intended to be heard as “Leck du mich im Arsch“, for which a relatively polite English rendering is “kiss my arse“.


Mozart displayed scatological humor in his letters and a few recreational compositions. This material has long been a puzzle for Mozart scholarship. One view held by scholars deals with the scatology by seeking an understanding of the role of it in Mozart’s family, his society and his times, while another view holds that such humor was the result of an “impressive list“ of psychiatric conditions from which Mozart is claimed to have suffered. For example, when Margaret Thatcher was apprised of Mozart’s scatology during a visit to the theater to see Peter Shaffer’s famous play, Amadeus, director Peter Hall relates: “She was not pleased. In her best headmistress style, she gave me a severe wigging for putting on a play that depicted Mozart as a scatological imp with a love of four-letter words. It was inconceivable, she said, that a man who wrote such exquisite and elegant music could be so foul mouthed“. I said that Mozart’s letters proved he was just that: he had an extraordinarily infantile sense of humor. “I don’t think you heard what I said,“ replied the Prime Minister. “He couldn’t have been like that.“ I offered (and sent) a copy of Mozart’s letters to Number Ten the next day; I was even thanked by the appropriate Private Secretary. But it was useless: the Prime Minister said I was wrong, so wrong I was.“


It has been suggested that there was a political underlay to the scatology in popular theater: its viewers lived under a system of hereditary aristocracy that excluded them from political participation. The vulgarity of scatological popular theater was a counterpoint to the refined culture imposed from above. One of Mozart’s own letters describes aristocrats in scatological terms; he identified the aristocrats present at a concert in Augsburg (1777) as “the Duchess Smackarse, the Countess Pleasurepisser, the Princess Stinkmess, and the two Princes Potbelly von Pigtail“. Although there is ample coverage of scatological humor in Mozart, there also exists scatological texts from Martin Luther, Johann Wolfgang von Goethe, Heinrich Heine, and other luminaries of German culture. Historian, Karhausen (1993) asserts that “Scatology was common in Mitteleuropa, [central Europe]“ noting for instance that Mozart’s Salzburg colleague Michael Haydn also wrote a scatological canon. In the 18th century, this type of humor did not show individual psychological impairment; it was public and “mainstream“.


The German-language popular theater of Mozart’s time was influenced by the Italian commedia dell’arte and emphasized the stock character of Hanswurst, a coarse and robust character who would entertain his audience by pretending to eat large and unlikely objects (for instance, a whole calf), then defecating them. There is a scene in the film, Amadeus, that depicts this activity using a large fake horse, on stage. An early 20th century observer who suspected that Mozart’s scatological materials could be interpreted by psychological pathologies was the Austrian writer Stefan Zweig, who amassed a large collection of musical manuscripts. His collection included the Basle letters (at the time, unpublished) as well as the autographs of Mozart’s scatological canons Difficile lectu and O du eselhafter Peierl Zweig sent copies of the Basle letters to the celebrated psychiatrist, Sigmund Freud, with the following suggestion:


These nine letters throw a psychologically very remarkable light on his erotic nature, which, more so than any other important man, has elements of infantilism and coprophilia. It would actually be a very interesting study for one of your pupils.


Wisely, Freud apparently declined Zweig’s suggestion.  It would seem that one genius recognized another.


As noted, later psycho-biographers seized on the letters as evidence for psychopathological tendencies in Mozart. The passage of time has created an almost unbridgeable gulf between ourselves and Mozart’s time, forcing us to misread his scatological letters even more drastically than his other letters. Very simply, these letters embarrass us, and we have tried to suppress them, trivialize them, or explain them out of the epistolary canon with pathological excuses. Some authors in the 1990s interpreted the material as evidence that Mozart had Tourette syndrome (TS). The letters were catalogued and then compared their scatologic frequencies with similar vulgarisms from other members of Mozart’s family – they are far more frequent. The scatological materials were combined with biographical accounts from Mozart’s own time that suggested that Mozart suffered from the tics characteristic of Tourette syndrome. This claim was picked up by newspapers worldwide, causing an international sensation, and internet websites have fueled the speculation. While often discussed, the Mozart/Tourette hypothesis has failed to sway mainstream opinion on this issue.


Historian Kammer (2007) states that the work proposing the hypothesis has been “promptly and harshly” criticized.  The critical commentary asserts both medical misdiagnosis and errors of Mozart scholarship. Kammer concluded that “Tourette’s syndrome is an inventive but implausible diagnosis in the medical history of Mozart”. Evidence of motor tics was found lacking and the notion that involuntary vocal tics are transferred to the written form was labeled “problematic”.  Neurologist and author Oliver Sacks published an editorial disputing the Tourettes claim, and the Tourette Syndrome Association pointed out the speculative nature of this information.  No Tourette’s syndrome expert or organization has voiced concurrence that there is credible evidence to conclude that Mozart had Tourette’s.  One TS specialist stated that, “although some web sites list Mozart as an individual who had Tourette’s and/or OCD, it’s not clear from the descriptions of his behavior that he actually had either.”


Wolfgang Amadeus Mozart died on 5 December 1791 at the age of 35. The circumstances of his death have attracted much research and speculation. Some principal sources of contention are as follows.


Whether Mozart declined gradually, experiencing great fear and sadness, or whether he was fundamentally in good spirits toward the end of his life, then felled by a relatively sudden illness. The former hypothesis held sway for most of the history of Mozart biography, but the latter has been advanced by contemporary scholars.


The actual cause of his death, whether it was from disease or poisoning. The poisoning hypothesis is widely discredited; but the particular disease that killed Mozart is unknown; only plausible conjectures can be offered.


His funeral arrangements, and whether they were the normal procedures of his day or rather, were neglectful and the basis for pathos. Here, modern scholarship generally supports the view that the funeral arrangements were normal for Mozart’s time.

Mozart’s wife, Constanze Mozart by her brother-in-law Joseph Lange (1782)


Mozart scholarship long followed the accounts of early biographers, which proceeded in large part from the recorded memories of his widow Constanze and her sister Sophie Weber as they were recorded in the biographies by Franz Niemetschek and Georg Nikolaus von Nissen. For instance, the important biography by Hermann Abert largely follows this account. The following is a summary of this view.


When in August 1791 Mozart’s arrived in Prague to supervise the performance of his new opera La clemenza di Tito, he was “already very ill“ (Abert, p. 1305). During this visit, Niemetschek wrote, “he was pale and expression was sad, although his good humour was often shown in merry jest with his friends.“ Following his return to Vienna (mid-September 1791), Mozart’s condition gradually worsened. For a while, he was still able to work and completed his Clarinet Concerto, worked toward the completion of his Requiem, and conducted the premiere performance of The Magic Flute on 30 September. Still, he became increasingly alarmed and despondent about his health. An anecdote from Constanze is related by Niemetschek: On his return to Vienna, his indisposition increased visibly and made him gloomily depressed. His wife was truly distressed over this. One day when she was driving in the Prater with him, to give him a little distraction and amusement, and they were sitting by themselves, Mozart began to speak of death, and declared that he was writing the Requiem for himself. Tears came to the eyes of the sensitive man: ?I feel definitely,’ he continued, ?that I will not last much longer; I am sure I have been poisoned. I cannot rid myself of this idea.’ Constanze attempted to cheer her husband by persuading him to give up work on the Requiem for a while, encouraging him instead to complete the “Freimaurerkantate“ (K. 623), composed to celebrate the opening of a new Masonic temple for Mozart’s own lodge. The strategy worked for a time – the cantata was completed and successfully premiered 18 November. He told Constanze he felt “elated“ over the premiere. Mozart is reported to have stated, “Yes I see I was ill to have had such an absurd idea of having taken poison, give me back the Requiem and I will go on with it.“


Even so, Mozart’s worst symptoms of illness soon returned, together with the strong feeling that he was being poisoned. He became bedridden on 20 November, suffering from swelling, pain and vomiting. From this point on, scholars are all agreed that Mozart was indeed very sick, and he died about two weeks later, on December 5 . However, there is still debate over Mozart’s health leading up to his untimely death, the view that Mozart was in near-steady decline and despair during the last several months of his life has met with skepticism in recent years. Some say that Mozart was under the weather in Prague, but there is no evidence that he was ?very ill’ and that it is not true that his health ?continued to deteriorate’. Some point to the fact that Mozart’s health improved in October and early November, which is no consolation, since Mozart died the following month. While later sources describe Mozart as working feverishly on his Requiem, filled with premonitions of his own death, these accounts are hard to reconcile with the high spirits of his letters from most of November. Constanze’s earliest account, published in Niemetschek’s biography of 1798, states that Mozart ?told her of his wish to try his hand at this type of composition, the more so as the higher forms of church music had always appealed to his genius.’ There is no hint that the work was a burden to him. As far as why Constanze might have been “prompted by complicated motives both personal and financial“, Halliwell contends that “Constanze and Sophie were not objective witnesses, because Constanze’s continuing quest for charity gave her reasons to disseminate sentimental and sensationalist views.“ By “charity“ Halliwell may be referring to the many benefit concerts from which Constanze received income in the years following Mozart’s death, as well as, perhaps, the pension she received from the Emperor; see discussion below as well as Constanze Mozart.


Benedikt Schack, Mozart’s close friend for whom he wrote the role of Tamino in The Magic Flute, told an interviewer that on the last day of Mozart’s life, he participated in a rehearsal of the Requiem in progress. Schack’s questionable account appeared in an obituary for Schack which was published in the 25 July 1827 issue of the Allgemeine musikalische Zeitung:


On the very eve of his death, Mozart had the score of the Requiem brought to his bed, and himself (it was two o’clock in the afternoon) sang the alto part; Schack, the family friend, sang the soprano line, as he had always previously done, Hofer, Mozart’s brother-in-law, took the tenor, Gerl, later a bass singer at the Mannheim Theater, the bass. They were at the first bars of the Lacrimosa when Mozart began to weep bitterly, laid the score on one side, and eleven hours later, at one o’clock in the morning (of 5 December 1791, as is well known), departed this life.


Another account stated that on the day of his death, Mozart asked for the score to be brought to his bedside. ?Did I not say before, that I was writing this Requiem for myself?’ After saying this, he looked yet again with tears in his eyes through the whole work. Sister-in-law, Sophie Weber did claim to recall, however, that Mozart gave instructions to a pupil. An 1840 letter from the composer Ignaz von Seyfried states that on his last night, Mozart was mentally occupied with the currently running opera The Magic Flute. Mozart is said to have whispered the following to Constanze in reference to her sister, Josepha Hofer, the coloratura soprano who premiered the role of the Queen of the Night:


“Quiet, quiet! Hofer is just taking her top F;- now my sister-in-law is singing her second aria, ?Der Holle Rache’; how strongly she strikes and holds the B-flat: ?Hort! hort! hort! der Mutter Schwur.“


Solomon, while noting that Mozart’s biographers often left out the “crueler memories“ surrounding his death, stated, “Constanze Mozart told Nissen that just before the end Mozart asked her what his physician Dr. Closset had said. When she answered with a soothing lie, he said, ?It isn’t true,’ and he was very distressed: ?I shall die, now when I am able to take care of you and the children. Ah, now I will leave you unprovided for.’ And as he spoke these words, ?suddenly he vomited – it gushed out of him in an arc – it was brown, and he was dead.’“ Mozart’s older, seven year-old son Karl, was present at his father’s death and later wrote, “Particularly remarkable is in my opinion that fact that a few days before he died, his whole body became so swollen that the patient was unable to make the smallest movement, moreover, there was stench, which reflected an internal disintegration which, after death, increased to the extent that an autopsy was impossible.“


The funeral arrangements were made by Mozart’s friend and patron Baron Gottfried van Swieten. Describing his funeral, the Grove Dictionary of Music and Musicians states, “Mozart was buried in a common grave, in accordance with contemporary Viennese custom, at the St. Marx Cemetery outside the city on 7 December.“ Otto Jahn wrote in 1856 that Salieri, Sussmayr, van Swieten and two other musicians were present. The common belief that Mozart was buried in a pauper’s grave is also without foundation. The “common grave“ referred to above is a term for a grave belonging to a citizen not of the aristocracy. It was an individual grave, not a communal grave; but after ten years the city had the right to dig it up and use it for a later burial. The graves of the aristocracy were spared such treatment. An element of poetry injected into the tale of Mozart’s death and funeral is a winter storm. A memoir attributed to one Joseph Deiner, who was claimed to have been present, appeared in the Vienna Morgen-Post of 28 January 1856, as follows:


The night of Mozart’s death was dark and stormy; at the funeral, too, it began to rage and storm. Rain and snow fell at the same time, as if Nature wanted to shew her anger with the great composer’s contemporaries, who had turned out extremely sparsely for his burial. Only a few friends and three women accompanied the corpse. Mozart’s wife was not present. These few people with their umbrellas stood round the bier, which then taken via the Grosse Schullerstrasse to the St. Marx Cemetery. As the storm grew ever more violent, even these few friends determined to turn back at the Stuben Gate, and they betook themselves to the “Silver Snake“. Deiner, the landlord, was also present for the funeral.


The above tale was widely adopted and incorporated into Mozart biographies. Deiner’s description of the weather is falsified by records kept at the time. The diarist Karl Zinzendorf recorded on 6 December that there had been “mild weather and frequent mist“. The Vienna Observatory kept weather records and recorded for 6 December a temperature ranging from 37.9 to 38.8 degrees Fahrenheit (2.8?C-3.8?C), with “a weak east wind at all times of the day.“ Following her husband’s death, Constanze recovered from her despair and addressed the task of providing financial security for her family; the Mozarts had two young children, and Mozart had died with outstanding debts. She successfully appealed to the Emperor on 11 December 1791 for a widow’s pension due to her as a result of Mozart’s service to the Emperor as a part-time chamber composer. Additionally, she organized a series of concerts of Mozart’s music and the publication of many of her husband’s works. As a result, Constanze became financially secure over time.


Soon after Mozart’s death, a Mozart biography was started by Friedrich Schlichtegroll, who wrote an early account based on information from Mozart’s sister, Nannerl. Working with Constanze, Franz Niemetschek wrote a biography as well. Much later, Constanze assisted her second husband, Georg Nikolaus von Nissen, on a more detailed biography published in 1826. Mozart’s musical reputation rose following his death; 20th-century biographer Maynard Solomon describes an “unprecedented wave of enthusiasm“ for his work after he died, and a number of publishers issued editions of his compositions. What may have been Mozart’s skull was exhumed in 1801, and in 1989-1991 it was examined for identification by several scientists.

Antonio Salieri portrayed by Joseph Willibrord Mahler


An early rumor addressing the cause of Mozart’s death was that he was poisoned by his colleague Antonio Salieri. This rumor, however, was not proven to be true as the signs of illness Mozart displayed did not indicate poisoning. Despite denying the allegation, Salieri was greatly affected by the accusations that he had contributed to Mozart’s death and contributed to his nervous breakdowns in later life. In the parish register, the entry concerning Mozart’s death states he died of “severe miliary fever“ – “miliary“ referring to the appearance of millet-sized bumps on the skin. This does not name the actual disease. Mozart had health problems throughout his life, suffering from smallpox, tonsillitis, bronchitis, pneumonia, typhoid fever, rheumatism, and gum disease. Whether these played any role in his demise cannot be determined. Conjectures as to what killed Mozart are numerous. The following survey is arranged in rough chronological order.


Some ascribe Mozart’s death to malpractice on the part of his physician, Dr. Closset. His sister-in-law Sophie Weber, in her 1825 account, makes the implication.


When Mozart appeared to be sinking, one of his doctors, Dr. Nikolaus Closset, was sent for and finally located at the theater. However, according to Sophie’s account, that drama-lover “had to wait till the piece was over.“ When he arrived, he ordered cold compresses put on Mozart’s feverish brow, but these “provided such a shock that he did not regain consciousness again before he died.


In a journal article dated 1908, it was suggested that Vitamin D deficiency could have played a role in Mozart’s underlying medical conditions leading to his death.


A suggestion is that Mozart died as a result of his hypochondriasis and his predilection for taking patent medicines containing antimony. In his final days, this was compounded by further prescriptions of antimony to relieve the fever he clearly suffered.


A 1994 article in Neurology suggests Mozart died of a subdural hematoma. A skull believed to be Mozart’s was saved by the successor of the gravedigger who had supervised Mozart’s burial, and later passed on to anatomist Josef Hyrtl, the municipality of Salzburg, and the Mozarteum museum (Salzburg). Forensic reconstruction of soft tissues related to the skull reveals substantial concordance with Mozart’s portraits. Examination of the skull suggested a premature closure of the metopic suture, which has been suggested on the basis of his physiognomy. A left temporal fracture and concomitant erosions raise the question of a chronic subdural hematoma, which would be consistent with several falls in 1789 and 1790 and could have caused the weakness, headaches, and fainting Mozart experienced in 1790 and 1791. Additionally, aggressive bloodletting used to treat suspected rheumatic fever could have decompensated such a lesion, leading to his death. In a 2000 publication, a team of two physicians (Faith T. Fitzgerald, Philip A. Mackowiak) and a musicologist (Neal Zaslaw) reviewed the historical evidence and tentatively opted for a diagnosis of rheumatic fever, and in 2009, British, Viennese and Dutch researchers performed epidemiological research combined with a study of other deaths in Vienna at the time of Mozart’s death. They concluded that Mozart may have died of a streptococcal infection leading to an acute nephritic syndrome caused by post streptococcal glomerulonephritis. This disease was also called “Wassersucht“ in Austria.


© Mozart – Clarinet concert in A – Martin Frost – DRSO – Thomas Sondergaard


Mozart: Magic Flute, (Act 1), tenor, Fritz Wunderlich: Tamino’s Portrait Aria

“Dies Bildnis“ Die Zauberflote


Mozart: Magic Flute. “Queen of the Night Aria“

Natalie Dessay as the Queen!


Mozart: Magic Flute, Sarastro’s first aria

Kurt Moll: Mozart – Die Zauberflote, ?O Isis und Osiris’


Art is the signature of civilizations.


Mozart: Magic Flute, Sarastro’s second aria

Ivashchenko sings Sarastro “Die Zauberflote“


Mozart: Magic Flute, Finale (Paris Opera)

Es lebe Sarastro, Sarastro soll leben!’



US Soldiers at Increased Suicide Risk After Leaving Hospital


According to results from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) study, published online in JAMA Psychiatry (12 November 2014) U.S. Army soldiers hospitalized with a psychiatric disorder have a significantly elevated suicide risk in the year following discharge from the hospital. The yearly suicide rate for this group, 263.9 per 100,000 soldiers, was far higher than the rate of 18.5 suicides per 100,000 in the Regular Army for the same study period. The authors looked at data from the 12 months following a hospital discharge for more than 40,000 anonymous, Regular Army soldiers (full-time soldiers excluding Army National Guard and Army Reserve) who served on active duty from 2004 through 2009.


This suicide rate began increasing in 2004, and exceeded the rate among a similar group of U.S. civilians in 2009, and has remained high through 2014. The current study of administrative data shows that 40,820 soldiers (0.8 percent of all Regular Army soldiers) were hospitalized with a psychiatric disorder in 2004-2009, the period covered by this research. Suicides occurring in this group during the year after a hospital discharge accounted for 12% of all Regular Army suicides during this period. The authors also found that it was possible to identify smaller, higher-risk groups within this at-risk population. Analyzing soldiers’ characteristics and experiences, it was possible to identify the 5% of soldiers with the highest predicted risk of suicide after leaving the hospital. This top 5% accounted for 52.9% of the post-hospital suicides. Soldiers in the top 5% also accounted for a greater proportion of accident deaths, suicide attempts, and re-hospitalizations.


The article also reported that for this group of hospitalized soldiers, some of the strongest predictors of suicide include being male, having enlisted at an older age, having a history of criminal offenses during Army service, having had prior suicidal thoughts or actions, as well as disorders diagnosed during hospitalization and aspects of prior psychiatric treatment. However, many other factors also contributed toward predicting suicide risk in this group, individually and in combination. This fact underscores the complexity of assessing suicide risk and the added value of developing new approaches to better predict very challenging events.


This is the first publication from Army STARRS that reports on the ability to use Army/Department of Defense data to identify specific subgroups within the Army that have very significantly elevated suicide risk, and there are sensitivities to using data to identify high-risk subgroups.


The authors concluded that the high concentration of suicide risk among this study group, and particularly in the smaller highest-risk groups, might justify targeting expanded post-hospital interventions for such people, and that researchers should continue to develop and refine computer models to help the Army predict suicide risk among soldiers and prevent self-harm.


Long Working Hours and Risk of Type 2 Diabetes


Working long hours might have adverse health effects, but whether this is true for all socioeconomic status groups is unclear. As a result, a meta-analysis published online in The Lancet Diabetes & Endocrinology (25 September 2014), investigated the role of long working hours as a risk factor for type 2 diabetes.


The study identified four published studies through a systematic literature search of PubMed and Embase up to April 30, 2014. Study inclusion criteria were English-language publication; prospective design (cohort study); investigation of the effect of working hours or overtime work; incident diabetes as an outcome; and relative risks, odds ratios, or hazard ratios (HRs) with 95% CIs, or sufficient information to calculate these estimates. Additionally, the authors used unpublished individual-level data from 19 cohort studies from the Individual-Participant-Data Meta-analysis in Working-Populations Consortium and international open-access data archives. Effect estimates from published and unpublished data from 222 120 men and women from the USA, Europe, Japan, and Australia were pooled with random-effects meta-analysis.


Results showed that during 1.7 million person-years at risk, 4,963 individuals developed diabetes (incidence 29/10,000 person-years). The minimally adjusted summary risk ratio for long (>55 hours per week) compared with standard working hours (35-40 hours) was 1.07 with significant heterogeneity in study-specific estimates (p=0.0016). In an analysis stratified by socioeconomic status, the association between long working hours and diabetes was evident in the low socioeconomic status group (risk ratio 1.29), but was null in the high socioeconomic status group (risk ratio 1.00). The association in the low socioeconomic status group was robust to adjustment for age, gender, obesity, and physical activity, and remained after exclusion of shift workers.


According to the authors, in this meta-analysis, the link between longer working hours and type 2 diabetes was apparent only in individuals in the low socioeconomic status groups.


Innovation Pathway at FDA


Take a look on the Target Health home page for a presentation on the innovative activities at FDA: How Creative One Can Be When Working with the FDA to Optimize the Drug and Device Development (NYMC, Oct 2014)


Patients deserve faster access to safe and effective medical devices that address unmet public health needs. The FDA’s Innovation Pathway is a new way of doing business within our existing regulatory framework that could yield significant benefits to patients in the U.S. by giving them first-in-the-world access to medical devices, including those with breakthrough technology. The Innovation Pathway is an evolving system designed to help safe, breakthrough medical products reach patients in a timely manner. The Pathway ultimately aims to shorten the overall time and cost it takes for the development, assessment and review of medical devices, and to improve how FDA staff and innovators work together. By engaging with innovators much earlier, more collaboratively, and in new ways, we believe we can reduce the time and cost of the entire process of bringing safe and effective technologies to patients more quickly.


On April 9, 2012, the FDA’s Center for Devices and Radiological Health (CDRH) launched its second version of the Innovation Pathway, called “Innovation Pathway 2.0.” Innovation Pathway 2.0 offers new and modified tools and methods to deepen collaboration between the FDA and innovators early in the process, prior to pre-market submission, with the goal of making the regulatory process more efficient and timely. The Pathway also serves as a living laboratory to test new tools and methods for breakthrough devices that we may also apply to other technologies to enhance all of our device pre-market programs.


For additional information, FDA has designated 4 websites addressing innovation:

  1. Driving Biomedical Innovation
  2. Innovation at CDER
  3. Innovation and Regulatory Science
  4. CDRH Medical Device Innovation Initiative


Pumpkin Risotto


Delicious side dish for your Thanksgiving Table  –  ©Joyce Hays, Target Health Inc.


Pumpkin Part of Risotto


3 large eggs

1/2 cup granulated Splenda

1/3 cup brown Splenda or other brown sugar substitute

1.5 cans (23-24-oz) pumpkin puree or 2.5 cups fresh pumpkin puree

3/4 cup evaporated milk

2 teaspoon vanilla extract

2 teaspoons ground cinnamon

1 teaspoon ground ginger

1/2 teaspoon ground cloves

1/2 teaspoon kosher salt


Directions for Pumpkin Ingredients


Make Pumpkin Part of the Risotto First:


In a mixing bowl, whisk eggs and both sugars together until smooth. Add the can of pumpkin puree, evaporated milk, vanilla, cinnamon, ginger, cloves and the salt. Stir until well blended. Set aside


Ingredients for the rest of the risotto


6 cups chicken or turkey stock or broth, more as needed

2 Tablespoons butter

2 Tablespoons olive oil

1 large onion, chopped

3 large cloves garlic, minced

1 and 1/2 cups arborio rice

1/4 teaspoon freshly grated nutmeg

1/3 cup dry white wine

Pumpkin mixture, divided (ingredients above)

Pinches, Salt and pepper

Pinch cayenne

1 teaspoon turmeric

1 cup water chestnuts, chopped

1 cup toasted pine nuts

Walnut oil

Grated Parmigiano-Reggiano, to taste


Directions for the entire recipe


  1. Toast the pine nuts and set aside


  1. In a medium saucepan, bring the chicken stock or vegetable broth to a simmer over medium heat.


  1. Meanwhile, in a large heavy-bottomed pot or Dutch oven, melt the butter and olive oil over medium heat. Stir in the onion and garlic, and cook, stirring frequently, until the onion is translucent and just begins to color, 8 to 10 minutes.




Stirring in the rice – ©Joyce Hays, Target Health Inc.


  1. Stir in the rice and nutmeg and cook, stirring frequently and coating the rice with the fat, until the rice just begins to toast, about 3 minutes.


  1. Add the wine and continue to stir, cooking until the wine is mostly absorbed.


  1. Add a ladleful of broth and cook, stirring constantly, until the broth is almost completely absorbed. Continue adding an additional ladle of broth as each is absorbed by the rice.


  1. After 10 minutes of cooking the rice, stir in half of the pumpkin mixture, with another ladle of broth. Season with one-half teaspoon salt and a pinch of pepper.


  1. Continue cooking the rice, stirring in additional broth as needed, until the rice is slightly al dente, about another 10 minutes.




Stirring in the remaining pumpkin mixture – ©Joyce Hays, Target Health Inc.


  1. Stir in the remaining pumpkin mixture, the toasted pine nuts and 2 Tablespoons walnut oil, the turmeric, chopped water chestnuts, cayenne. Stir in additional broth as desired for a creamy consistency.


  1. Serve each portion with a light drizzle of walnut oil and a sprinkling of freshly grated cheese (optional – I didn’t, I simply sprinkled a few pine nuts on top)


This is the fourth incarnation of my pumpkin risotto. I just couldn’t seem to get the right balance of sweet and savory. Either it was too bland, or when I added candied chestnuts, it was too sweet. I was trying to create a dish to serve on Thanksgiving and afterwards with leftovers, like the turkey croquettes recipe from last week. I think I finally got the right amounts of ingredients; Jules says, he gives it a 4.5 to 5 out of 5 stars, but you be the final judge.


We started this meal with red and white wine, a salad: beautiful ripe tomatoes, shredded endive, avocados cut into cubes, green olives and thinly sliced cucumbers (the kind with thin skin, you don’t want/have to remove). The dressing was a simple olive oil and fresh lemon juice. The entre was left-over turkey slices with stuffing and the pumpkin risotto. Just happened to have pomegranate arils on hand so we sprinkled some of those over the turkey. This was a scrumptious meal!




We’re drinking a new red, Pinot Noir, from Paul Hobbs vineyards in CA, in addition to Santa Margherita, Pinot Grigio


This past week, we saw Magic Flute at the MetOpera, one of our favorite operas at the Met. Needless to say, Mozart’s music was sublime from start to finish. This has got to be the perfect opera! Voices were top notch, the brilliant Julie Taymor production could not be improved upon. Our experience of this opera was of the highest level. Days later, my mind is still swirling with the arias of Tamino, Papageno, Sarastro, Queen of the Night, Pamina and Papagena. I’ve been obsessed with Mozart. It’s no wonder that I had to do the History of Medicine on this especially rare genius. We also watched the film, Amadeus, which we saw years ago, but loved it again as if for the first time.


Hope you enjoy some of the musical links provided in this week’s newsletter.


From Our Table to Yours!


Bon Appetit!