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#FEM #RES.2-002 #linear-analysis
My objective in this set of lectures is to introduce to you finite element methods for the linear analysis of solids and structures. ["Iinear" meaning infinitesimally small displacements and linear elastic material properties (Hooke's law applies)]
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#MIT #jenga

Jenga is a quintessential example of a contact rich task where we need to interact with the tower to learn and infer block mechanics and multi-modal behavior by combining touch and sight.

Current learning methodologies struggle with these challenges and have not exploited physics nearly as richly as we believe humans do. Most robotic learning systems still use purely visual data, without a sense of touch; this fundamentally limits how quickly and flexibly a robot can learn about the world. Learning algorithms that build on model-free reinforcement learning methods have little to no ability to exploit knowledge about the physics of objects and actions. Even the methods using model-based reinforcement learning or imitation learning have mostly used generic statistical models that do not explicitly represent any of the knowledge about physical objects, contacts, or forces that humans have from a very early age. As a consequence, these systems require far more training data than humans do to learn new models or new tasks, and they generalize much less broadly and less robustly.

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#algorithmic-advances #deep-learning #machine-learning
Because the field is guided by experimental findings rather than by theory, algorithmic advances only become possible when appropriate data and hardware are available to try new ideas (or scale up old ideas, as is often the case). Machine learning isn’t mathematics or physics, where major advances can be done with a pen and a piece of paper. It’s an engineering science.
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#34 #41 #Cours #Facultaires #Gynécologie #Hémorragies #Menstruels #Médecine #Troubles

  • Les menstruations normales durent entre 3 et 6 jours et correspondent à des pertes sanguines < 80 mL.
  • Les ménorragies sont des menstruations trop abondantes en volume ou en durée
  • Les métrorragies sont des saignements génitaux entre les périodes de menstruation
  • Les ménométrorragies correspondent à l'association de ménorragies et de métrorragies

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#34 #41 #Cours #Facultaires #Gynécologie #Hémorragies #Menstruels #Médecine #Troubles

Le score de Higham (fig. 4.1) permet une évaluation objective de la quantité des saignements.

  • Durant les menstruations, la femme note chaque jour le nombre de serviettes et/ou de tampons dans la case correspondant au degré d'imprégnation de la protection. Elle rapporte également les épisodes de caillots et de pertes majeures. On additionne ensuite le nombre de points par jour.
  • On parle de ménorragies pour un score de Higham supérieur à 100

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#34 #41 #Cours #Facultaires #Gynécologie #Hémorragies #Menstruels #Médecine #Troubles

Bilan biologique

Il comporte :

  • β-hCG plasmatiques ou urinaires systématiques chez toute patiente en âge de procréer
  • NFS
  • bilan martial :
    • ferritinémie + CRP (car un syndrome inflammatoire peut masquer une hypoferritinémie)
  • bilan d'hémostase (TP, TCA), dosage du facteur de Willebrand pour recherche de maladie de Willebrand (d'indication large chez l'adolescente)

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#34 #41 #Cours #Facultaires #Gynécologie #Hémorragies #Menstruels #Médecine #Troubles

Hystéroscopie diagnostique :

  • Elle se fait en consultation.
  • Elle est à réaliser préférentiellement en 1ère partie de cycle et après s'être assuré de l'absence de grossesse.
  • On utilise préférentiellement du sérum physiologique pour la distension de la cavité, et un hystéroscope rigide de faible calibre.
  • L'hystéroscopie permet de visualiser la cavité utérine : aspect de l'endomètre, présence d'un polype ou d'un myome.
  • Elle est à pratiquer en cas d'anomalie à l'échographie ou en cas d'échec de traitement médicamenteux avec échographie normale.

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#34 #41 #Cours #Facultaires #Gynécologie #Hémorragies #Menstruels #Médecine #Troubles

Biopsie d'endomètre :

  • Elle doit être faite chez toute patiente de plus de 45 ans ou en cas de facteur de risque de cancer de l'endomètre.
  • Le prélèvement est effectué à la pipelle de Cornier ® , après éventuelle hystéroscopie diagnostique.

  • Il est également possible d'effectuer des biopsies dirigées lors d'une hystéroscopie diagnostique (grâce à une pince à travers un canal opérateur).
  • Le but de la biopsie est de diagnostiquer un cancer de l'endomètre ou une hyperplasie glandulaire atypique.

  • Attention, la biopsie est généralement faite à l'aveugle et ne peut éliminer avec certitude un cancer de l'endomètre, même si elle est normale ++

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#34 #41 #Cours #Facultaires #Gynécologie #Hémorragies #Menstruels #Médecine #Troubles

À ne pas faire devant des métrorragies

  • Le résultat d'un frottis cervico-utérin est faussé par la présence de sang.
  • Une hystérosalpingographie est inutile

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#34 #41 #Cours #Facultaires #Gynécologie #Hémorragies #Menstruels #Médecine #Troubles

Polype :

  • On procède à une résection par hystéroscopie opératoire ; on peut y associer une endométrectomie en cas d'absence de désir de grossesse

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#34 #41 #Cours #Facultaires #Gynécologie #Hémorragies #Menstruels #Médecine #Troubles

Adénomyose :

  • Le traitement repose sur un DIU au lévonorgestrel en 1ère intention, la chirurgie en 2ème intention (endométrectomie ou hystérectomie en cas d'échec ou de refus ; en l'absence de désir de grossesse)

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#34 #41 #Cours #Facultaires #Gynécologie #Hémorragies #Menstruels #Médecine #Troubles

Myome

• Le traitement médical (mise en aménorrhée) repose sur les progestatifs (21 jours/mois ou en continu), l'acétate d'ulipristal ou les agonistes de la GnRH (associer une hormonothérapie de substitution œstroprogestative type add-back thérapie selon la durée du traitement).

• Le traitement chirurgical consiste en une résection hystéroscopique pour les myomes sous- muqueux de type 0, 1 ou 2 de la FIGO (fig. 4.2 et tableau 4.3), de moins de 3 ou 4 cm.

• Pour les myomes interstitiels et sous-séreux, le traitement médical est instauré en 1 re inten- tion (DIU au lévonorgestrel, progestatif ou acétate d'ulipristal). En cas d'échec, la chirurgie est discutée, à type de myomectomie par laparoscopie ou laparotomie en cas de désir de traitement conservateur. S'il n'y a plus de désir de grossesse, on peut proposer une hystérectomie interannexielle avec salpingectomie bilatérale.

• Il existe une possibilité de traitement par embolisation utérine (non recommandé en cas de désir de grossesse).

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#34 #41 #Cours #Facultaires #Gynécologie #Hémorragies #Menstruels #Médecine #Troubles
Hyperplasie glandulaire endométriale sans atypie Le traitement est médical par progestatifs per os ou DIU au lévonorgestrel. En cas d'échec et en dehors d'un désir de grossesse, il est possible d'envisager un traitement chirurgical conser- vateur à type d'endométrectomie
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#34 #41 #Cours #Facultaires #Gynécologie #Hémorragies #Menstruels #Médecine #Troubles

Hyperplasie glandulaire atypique :

  • En cas de désir de grossesse, le traitement est conservateur par progestatifs, agonistes de la GnRH ou DIU au lévonorgestrel avec contrôle hystéroscopique et biopsie d'endomètre à 6 mois.
    • En l'absence de conception ou à 6 mois du post-partum, il est recommandé de réaliser une hystérectomie totale du fait du risque d'évolution vers un adénocarcinome de l'endomètre.
  • En l'absence de désir de grossesse, le traitement consiste en une hystérectomie totale ± annexectomie bilatérale du fait du risque de méconnaître un cancer de l'endomètre

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#34 #41 #Cours #Facultaires #Gynécologie #Hémorragies #Menstruels #Médecine #Troubles

Malformation artérioveineuse

  • Elle est traitée par embolisation radiologique (non délétère sur la fonction ovarienne et préserve la fertilité).
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#34 #41 #Cours #Facultaires #Gynécologie #Hémorragies #Menstruels #Médecine #Troubles

Ménométrorragies provoquées (ou post-coïtales)

  • Elles doivent faire rechercher une pathologie du col utérin (cancer du col +++, ectropion).
  • En présence d'une masse cervicale à l'examen sous spéculum, il faut faire une colposcopie associée à des biopsies.

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#34 #41 #Cours #Facultaires #Gynécologie #Hémorragies #Menstruels #Médecine #Troubles

Ménométrorragies idiopathiques :

  • Elles sont traitées par contraceptifs oraux progestatifs et œstroprogestatifs ou DIU au lévonorgestrel, acide tranexamique en cas de contre-indication aux traitements hormonaux ou de désir de grossesse.
  • En l'absence de désir de grossesse, un traitement chirurgical est proposé (endométrectomie par résection hystéroscopique ou par thermodestruction, hystérectomie en cas d'échec des traitements précédents). Les possibilités de traitement chirurgical sont limitées en cas de désir de grossesse.

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#35 #Contraception #Cours #Facultaires #Gynécologie #Médecine

  • Le choix d'une méthode déterminée dépend en partie de son efficacité contraceptive, laquelle est elle-même fonction non seulement de la protection conférée par la méthode, mais aussi de la régularité et de la rigueur avec lesquelles elle est employée.
  • L'efficacité d'une méthode contraceptive se mesure par l'indice de Pearl qui correspond au rapport du nombre de grossesses accidentelles pour 100 femmes après 12 mois d'utilisation

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#35 #Contraception #Cours #Facultaires #Gynécologie #Médecine

Contraception œstroprogestative (COP) - Mécanismes d'action :

  • L'effet contraceptif de la COP agit par plusieurs mécanismes :
    • action antigonadotrope du composé progestatif principalement (amplifiée par l'œstrogène), supprimant ainsi le pic ovulatoire de LH et FSH et inhibant la croissance folliculaire
    • modification de la glaire cervicale, épaisse et moins abondante (composé progestatif)
    • atrophie de l'endomètre le rendant plus ou moins inapte à la nidation (composé progestatif)

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#35 #Contraception #Cours #Facultaires #Gynécologie #Médecine

L'œstrogène et le progestatif sont administrés conjointement à différentes doses.

  • Si la dose des deux composés est fixe tout au long du cycle, on parle de pilule combinée monophasique ; on parle de pilule combinée biphasique lorsque deux séquences de dosages existent (plus forte posologie en 2 e partie de plaquette) ou de pilule combinée triphasique lorsque trois phases de dosages sont utilisées

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#35 #Contraception #Cours #Facultaires #Gynécologie #Médecine

La COP reste la contraception utilisée de 1ère intention chez la femme jeune sans aucun facteur de risque.

Il est recommandé de prescrire en 1ère intention une COP de 2 e génération par voie orale en raison du risque thromboembolique moins élevé qu'avec toutes les autres générations de COP et toutes les autres voies d'administration.

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#35 #Contraception #Cours #Facultaires #Gynécologie #Médecine

Contre-indications - Elles sont :

  • D'ordre carcinologique :
    • tumeurs malignes du sein ou de l'utérus (endomètre)
  • Métaboliques :
    • dyslipidémie
    • diabète mal équilibré ou compliqué
  • Vasculaires :
    • thrombophilie biologique
    • hypertension artérielle
    • migraine avec aura
    • tabagisme important
    • antécédents personnels ou familiaux d'évènements thromboemboliques veineux ou d'affections cardiovasculaires artérielles (IDM, AVC ischémique, artériopathie oblitérante des membres inférieurs)
    • âge > 35–40 ans surtout lorsqu'il existe des facteurs de risque cardiovasculaire associés
  • Hépatiques et biliaires (antécédent de lithiase)
  • Représentées par les pathologies hormonodépendantes vis-à-vis de la progestérone (méningiomes, etc.) et vis-à-vis des œstrogènes (lupus évolutif par exemple).

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#35 #Contraception #Cours #Facultaires #Gynécologie #Médecine

Effets indésirables (majeurs ou mineurs) :

Ils sont essentiellement d'ordre vasculaire et métabolique :

  • Augmentation du risque thromboembolique veineux en raison des modifications de l'hémostase induites pharmacologiquement par les stéroïdes contenus dans les COP et dépendant du climat hormonal de chaque pilule.
  • Ce sont les pilules combinées de 2 ème génération contenant du lévonorgestrel qui sont le moins à risque comparativement aux COP contenant des progestatifs de 3ème génération, de la drospirénone ou de l'acétate de cyprotérone.
  • Le risque thromboembolique existe même avec les pilules de 2ème génération. Ce risque relatif est de l'ordre de 3 comparé aux femmes non utilisatrices.

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#35 #Contraception #Cours #Facultaires #Gynécologie #Médecine

Augmentation du risque artériel (risque d'infarctus du myocarde ou d'accident vasculaire cérébral) principalement chez les femmes à risque artériel car la COP modifie certains métabolismes et a une action synergique dans certaines situations cliniques comme suit :

  • Métabolisme glucidique par diminution de la tolérance au glucose entraînant un certain degré d'insulinorésistance
  • Métabolisme lipidique : dépendant du climat hormonal de la COP avec augmentation des triglycérides, du cholestérol total et du HDL-cholestérol
  • Apparition d'une hypertension artérielle chez environ 5 % des femmes probablement en relation avec des modifications de l'angiotensinogène
  • Tabac : ce risque artériel est majoré chez les femmes qui fument sans que la quantité de tabac ne soit clairement déterminée. Le risque est proportionnel à la quantité de tabac
  • Migraine : avec un effet synergique de la COP très significatif chez les femmes souffrant de migraines avec aura
  • Antécédents familiaux du 1 er degré chez des apparentés jeunes (< 60 ans) : action synergique de la COP
  • Obésité ou surpoids : action synergique de la COP
  • Âge > 35 ans : action synergique de la COP

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#35 #Contraception #Cours #Facultaires #Gynécologie #Médecine

Les COP sont associées très probablement à une très discrète augmentation du risque de cancer du sein ainsi que du col de l'utérus (chez les femmes HPV +).

Ces effets indésirables sont largement contrebalancés par d'autres effets bénéfiques carcinologiques. Notons aussi une augmentation du risque de lithiase biliaire

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#35 #Contraception #Cours #Facultaires #Gynécologie #Médecine

Les effets bénéfiques suivants doivent être pris en compte :

  • Diminution du risque de cancer de l'ovaire (environ 50 %, durée-dépendante, d'où l'absence de contre-indication de la COP chez les femmes présentant des mutations BRCA1 ou BRCA2)
  • Diminution du risque de cancer de l'endomètre
  • Diminution du risque de cancer du côlon et du rectum
  • Amélioration des dysménorrhées, des ménorragies fonctionnelles et de l'acné (quel que soit le type de COP).

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#35 #Contraception #Cours #Facultaires #Gynécologie #Médecine

Progestatifs à faibles doses (microprogestatifs) - Mécanismes d'action :

L'effet contraceptif des progestatifs à faibles doses agit par plusieurs mécanismes :

  • Principalement par modification de la glaire cervicale (épaisse et donc impropre au passage des spermatozoïdes), d'où l'importance d'une utilisation en continu
  • Par possible atrophie de l'endomètre, inapte à la nidation
  • Par diminution de la mobilité tubaire
  • Pour le désogestrel, par une discrète action antigonadotrope, variable selon les femmes (action anti-ovulatoire par écrêtement du pic de LH)

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#35 #Contraception #Cours #Facultaires #Gynécologie #Médecine

Ces petites doses de progestatif délivrées en continu peuvent être utilisées selon plusieurs voies d'administration :

• par voie orale : leur action contraceptive est essentiellement périphérique. Dénuée d'effets indésirables métaboliques et vasculaires, il s'agit de l'une des méthodes contraceptives de 1er choix pour les femmes présentant des contre-indications métaboliques et vasculaires, en post-partum immédiat ou lors de l'allaitement.

• par voie sous-cutanée : l'implant contraceptif délivre quotidiennement de faibles doses d'étonogestrel à des taux plasmatiques proches de ceux des microprogestatifs. Il est posé sous la peau à la face interne du bras non dominant après une anesthésie locale. Sa durée d'action est de 3 ans.

• par voie intra-utérine : le DIU au lévonorgestrel entraîne une atrophie de l'endomètre et un épaississement de la glaire cervicale. Sa durée d'utilisation est de 5 ans pour la forme classique et de 3 ans pour la taille plus petite. Il est spécialement indiqué en cas de dysménorrhées, de ménorragies fonctionnelles et d'adénomyose

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#35 #Contraception #Cours #Facultaires #Gynécologie #Médecine

Contre-indications

Les contre-indications formelles sont :

  • Les pathologies hépatiques évolutives
  • Le cancer du sein
  • Les kystes fonctionnels à répétition
  • Les antécédents de grossesse extra-utérine
  • Les pathologies hormonodépendantes vis-à-vis de la progestérone (méningiome, etc.)

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#Endocrinologie #Guyton #Gynécologie #Médecine #Physiologie #Reproduction
Female reproductive functions can be divided into two major phases: (1) preparation of the female body for con- ception and pregnancy and (2) the period of pregnancy itself.
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#Endocrinologie #Guyton #Gynécologie #Médecine #Physiologie #Reproduction
A developing egg (oocyte) differentiates into a mature egg (ovum) through a series of steps called oogenesis (Figure 82-3).
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#Endocrinologie #Guyton #Gynécologie #Médecine #Physiologie #Reproduction
Once these primordial germ cells reach the germinal epithelium, they migrate into the substance of the ovarian cortex and become oogonia or primordial ova
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#Endocrinologie #Guyton #Gynécologie #Médecine #Physiologie #Reproduction
Each primordial ovum then collects around it a layer of spindle cells from the ovarian stroma (the supporting tissue of the ovary) and causes them to take on epithelioid characteristics; these epithelioid-like cells are then called granulosa cells.
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#Endocrinologie #Guyton #Gynécologie #Médecine #Physiologie #Reproduction
granulosa cells. The ovum surrounded by a single layer of granulosa cells is called a primordial follicle. At this stage the ovum is still immature and is called a primary oocyte, requiring two more cell divisions before it can be fertilized by a sperm.
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#Endocrinologie #Guyton #Gynécologie #Médecine #Physiologie #Reproduction
The oogonia in the embryonic ovary complete mitotic replication and the first stage of meiosis by the fifth month of fetal development.
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#Endocrinologie #Guyton #Gynécologie #Médecine #Physiologie #Reproduction
The first meiotic division of the oocyte occurs after puberty. Each oocyte divides into two cells, a large ovum (secondary oocyte) and a small first polar body
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#Endocrinologie #Guyton #Gynécologie #Médecine #Physiologie #Reproduction
When the ovary releases the ovum (ovulation) and if the ovum is fertilized, the final meiosis occurs. Half of the sister chromatids remain in the fertilized ovum and the other half are released in a second polar body, which then disintegrates
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#Endocrinologie #Guyton #Gynécologie #Médecine #Physiologie #Reproduction
During all the reproductive years of adult life, between about 13 and 46 years of age, only 400 to 500 of the primordial follicles develop enough to expel their ova—one each month; the remainder degenerate (i.e., become atretic). At the end of reproductive capability (at menopause), only a few primordial follicles remain in the ovaries, and even these follicles degenerate soon thereafter.
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#Endocrinologie #Guyton #Gynécologie #Médecine #Physiologie #Reproduction

The female hormonal system, like that of the male hormonal system, consists of three hierarchies of hormones, as follows:

1. A hypothalamic releasing hormone, called gonadotropin-releasing hormone (GnRH)

2. The anterior pituitary sex hormones, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), both of which are secreted in response to the release of GnRH from the hypothalamus

3. The ovarian hormones, estrogen and progesterone, which are secreted by the ovaries in response to the two female sex hormones from the anterior pituitary gland These various hormones are secreted at drastically differing rates during different parts of the female monthly sexual cycle.

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#Endocrinologie #Guyton #Gynécologie #Médecine #Physiologie #Reproduction
The amount of GnRH released from the hypothalamus increases and decreases much less drastically during the monthly sexual cycle. It is secreted in short pulses averaging once every 90 minutes, as occurs in the male.
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#Endocrinologie #Guyton #Gynécologie #Médecine #Physiologie #Reproduction
This rhythmical pattern is called the female monthly sexual cycle (or, less accurately, the menstrual cycle). The duration of the cycle averages 28 days. It may be as short as 20 days or as long as 45 days in some women, although abnormal cycle length is frequently associated with decreased fertility
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The ovarian changes that occur during the sexual cycle depend completely on the gonadotropic hormones FSH and LH, which are secreted by the anterior pituitary gland. Both FSH and LH are small glycoproteins that have molecular weights of about 30,000.
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At age 9 to 12 years, the pituitary begins to secrete progressively more FSH and LH, which leads to the onset of normal monthly sexual cycles beginning between the ages of 11 and 15 years. This period of change is called puberty, and the time of the first menstrual cycle is called menarche.
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Almost all these stimulatory effects result from activation of the cyclic adenosine monophosphate second messenger system in the cell cytoplasm, which causes the formation of protein kinase and multiple phosphorylations of key enzymes that stimulate sex hormone synthesis, as explained in Chapter 75
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#Apprentissage #Culture #Learning #Sleep #Sommeil

Modern society has developed a set of well-entrenched rules that keep sleep in utmost disregard. This has been driven to pathological levels in American society. Here are some bad rules that hurt sleep:

  • it is ok to use an alarm clock to cut sleep short
  • it is ok to work in shifts
  • it is ok to travel people around the world without much attention to the jet lag problem
  • it is ok to save time by sleeping less and working more
  • it is ok to pull kids out of bed in time for school
  • it is ok to skip nights before important exams, etc.
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Good sleep, good learning, good life
leep plays a critical physiological function, and is indispensable for your intellectual development! Those who do not respect their sleep are not likely to live to their full mental potential! <span>Modern society has developed a set of well-entrenched rules that keep sleep in utmost disregard. This has been driven to pathological levels in American society. Here are some bad rules that hurt sleep: it is ok to use an alarm clock to cut sleep short it is ok to work in shifts it is ok to travel people around the world without much attention to the jet lag problem it is ok to save time by sleeping less and working more it is ok to pull kids out of bed in time for school it is ok to skip nights before important exams, etc. Cutting down on sleep does not make people die (at least not immediately). It does make them feel miserable, but the ease with which we recover by getting just one good night of sleep s




#Apprentissage #Culture #Learning #Sleep #Sommeil

When Barack Obama was asked about his most desired Christmas gift after over a year of campaigning for president, he answered without hesitation: 8 hours of sleep.

The bad example of disrespect for sleep comes from the most important people in the nation!

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of November 7, 2000. After the election, Gore still kept on his feet by going into extra hours of the concede-retract cycle of his cliffhanger contest against Governor George W. Bush of Texas. <span>When Barack Obama was asked about his most desired Christmas gift after over a year of campaigning for president, he answered without hesitation: 8 hours of sleep. The bad example of disrespect for sleep comes from the most important people in the nation! Yet some dramatic facts related to sleep deprivation have slowly come into light. Each year sleep disorders add $16 billion to national health-care costs (e.g. by contributing to high b




#Apprentissage #Culture #Learning #Sleep #Sommeil
For this, the National Commission on Sleep Disorders estimates that sleep deprivation costs $150 billion a year in higher stress and reduced workplace productivity[1]
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ear sleep disorders add $16 billion to national health-care costs (e.g. by contributing to high blood pressure and heart disease). That does not include accidents and lost productivity at work. <span>For this, the National Commission on Sleep Disorders estimates that sleep deprivation costs $150 billion a year in higher stress and reduced workplace productivity[1]. 40% of truck accidents are attributable to fatigue and drowsiness, and there is an 800% increase in single vehicle commercial truck accidents between midnight and 8 am. Major industria




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Major industrial disasters have been attributed to sleep deprivation (Mitler et al. 1988[2])(incl. Three Mile Island, Chernobyl, the gas leak at Bhopal, Zeebrugge disaster, and the Exxon Valdez oil spill).

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rkplace productivity[1]. 40% of truck accidents are attributable to fatigue and drowsiness, and there is an 800% increase in single vehicle commercial truck accidents between midnight and 8 am. <span>Major industrial disasters have been attributed to sleep deprivation (Mitler et al. 1988[2])(incl. Three Mile Island, Chernobyl, the gas leak at Bhopal, Zeebrugge disaster, and the Exxon Valdez oil spill). It has been known since the 1920s that sleep improves recall in learning. However, only at the turn of the millennium, research by Dr Robert Stickgold, Associate Professor of Psychiatry




#Apprentissage #Culture #Learning #Sleep #Sommeil
Dr Stickgold's research proves a fact that has long been known yet little appreciated: sleep is necessary for learning (Stickgold 2005[3])! With less sleep, we reduce the recall of facts we learned before or after a shortened night. Studying nights before an exam may be sufficient for passing the exam, yet it will leave few useful traces in long-term memory. The exam on its own replaces knowledge as the main purpose of studying!
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recall in learning. However, only at the turn of the millennium, research by Dr Robert Stickgold, Associate Professor of Psychiatry at Harvard Medical School, has made international headlines. <span>Dr Stickgold's research proves a fact that has long been known yet little appreciated: sleep is necessary for learning (Stickgold 2005[3])! With less sleep, we reduce the recall of facts we learned before or after a shortened night. Studying nights before an exam may be sufficient for passing the exam, yet it will leave few useful traces in long-term memory. The exam on its own replaces knowledge as the main purpose of studying! By cutting down on sleep, we learn less, we develop less, we are less bright, we make worse decisions, we accomplish less, we are less productive, we are more prone to errors, and we un




#Apprentissage #Culture #Learning #Sleep #Sommeil
A change in societal sleep habits can spell a social revolution in learning, health, and productivity on a scale that few imagine! "Judging from history, it would seem that fundamental changes in the way we think about sleep will be required for policy changes that would protect society from sleepy people who make catastrophic errors in industry and transportation" (Merrill Mitler, PhD)
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rn less, we develop less, we are less bright, we make worse decisions, we accomplish less, we are less productive, we are more prone to errors, and we undermine our true intellectual potential! <span>A change in societal sleep habits can spell a social revolution in learning, health, and productivity on a scale that few imagine! "Judging from history, it would seem that fundamental changes in the way we think about sleep will be required for policy changes that would protect society from sleepy people who make catastrophic errors in industry and transportation" (Merrill Mitler, PhD) I have studied student personalities among users of SuperMemo for over twenty years now. There are a couple of determinants that make a good, efficient and persistent student. Here are




#Apprentissage #Culture #Learning #Sleep #Sommeil

I have studied student personalities among users of SuperMemo for over twenty years now. There are a couple of determinants that make a good, efficient and persistent student. Here are some characteristics of a person who is likely to be successful in learning:

  • highly optimistic
  • sleeps well
  • knowledge hungry
  • stress-tolerant
  • energetic, but able to slow down at the time of learning
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the way we think about sleep will be required for policy changes that would protect society from sleepy people who make catastrophic errors in industry and transportation" (Merrill Mitler, PhD) <span>I have studied student personalities among users of SuperMemo for over twenty years now. There are a couple of determinants that make a good, efficient and persistent student. Here are some characteristics of a person who is likely to be successful in learning: highly optimistic sleeps well knowledge hungry stress-tolerant energetic, but able to slow down at the time of learning Here are some unfortunate characteristics that do not correlate well with the ability to study effectively: prone to depression or mood swings problems with sleep (esp. insomnia) high l




#Apprentissage #Culture #Learning #Sleep #Sommeil

Here are some unfortunate characteristics that do not correlate well with the ability to study effectively:

  • prone to depression or mood swings
  • problems with sleep (esp. insomnia)
  • high levels of stress
  • hyperactive and unfocused
  • low stress tolerance (smokers, abusers of mood altering substances, drinkers, etc.)
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e characteristics of a person who is likely to be successful in learning: highly optimistic sleeps well knowledge hungry stress-tolerant energetic, but able to slow down at the time of learning <span>Here are some unfortunate characteristics that do not correlate well with the ability to study effectively: prone to depression or mood swings problems with sleep (esp. insomnia) high levels of stress hyperactive and unfocused low stress tolerance (smokers, abusers of mood altering substances, drinkers, etc.) Sleeping well appears to be one of the most important factors underlying success in learning! Why do we sleep? For many years, the physiological function of sleep has not been clear. In




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Restorative, protective and energy-conserving theories of sleep have been quite popular until quite recently, when it has become apparent that one long-lasting sleep episode with suppression of consciousness does not seem to be the right way for evolution to tackle depleted resources, toxic wastes, or energy conservation.
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cess in learning! Why do we sleep? For many years, the physiological function of sleep has not been clear. In most people's mind, sleep is associated with rest and time for mental regeneration. <span>Restorative, protective and energy-conserving theories of sleep have been quite popular until quite recently, when it has become apparent that one long-lasting sleep episode with suppression of consciousness does not seem to be the right way for evolution to tackle depleted resources, toxic wastes, or energy conservation. For example, muscles do not need to shut off completely to get rest. The critical function of sleep is dramatically illustrated in experiments in which rats chronically deprived of slee




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The critical function of sleep is dramatically illustrated in experiments in which rats chronically deprived of sleep eventually die usually within 2.5 weeks (for more see: If you do not sleep, you die!).

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iousness does not seem to be the right way for evolution to tackle depleted resources, toxic wastes, or energy conservation. For example, muscles do not need to shut off completely to get rest. <span>The critical function of sleep is dramatically illustrated in experiments in which rats chronically deprived of sleep eventually die usually within 2.5 weeks (for more see: If you do not sleep, you die!). In evolutionary terms, sleep is a very old phenomenon and it clearly must play a role that is critical to survival. Only quite recently, it has been proven beyond doubt that the functio




#Apprentissage #Culture #Learning #Sleep #Sommeil
In evolutionary terms, sleep is a very old phenomenon and it clearly must play a role that is critical to survival. Only quite recently, it has been proven beyond doubt that the function of sleep is related to learning (not all scientists agree) !
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l function of sleep is dramatically illustrated in experiments in which rats chronically deprived of sleep eventually die usually within 2.5 weeks (for more see: If you do not sleep, you die!). <span>In evolutionary terms, sleep is a very old phenomenon and it clearly must play a role that is critical to survival. Only quite recently, it has been proven beyond doubt that the function of sleep is related to learning (not all scientists agree)! Researchers have long known about the importance of the hippocampus, a small brain organ, for memory formation. Yet it has always been difficult to find out what is special about the hi




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Ground-breaking theories of Dr György Buzsáki and his two-stage model of memory trace formation have shed new light on what might actually be happening during sleep (Buzsáki 1989[4])(important: do not confuse this two-stage model with the two-component model of memory (Wozniak et al 1995[5]) or with the two-component model of sleep regulation (Borbely 1982[6]) below)
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ective effort of a number of researchers resulted in the proposition of the concept of neural optimization in sleep (see the next section for a metaphorical explanation: Disk and RAM metaphor). <span>Ground-breaking theories of Dr György Buzsáki and his two-stage model of memory trace formation have shed new light on what might actually be happening during sleep (Buzsáki 1989[4])(important: do not confuse this two-stage model with the two-component model of memory (Wozniak et al 1995[5]) or with the two-component model of sleep regulation (Borbely 1982[6]) below). Using his knowledge of neural networks, ingenious experiments on neuronal firing, and sophisticated mathematical analysis of spatiotemporal neuronal firing patterns, Buzsáki provided a




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The hippocampus acts as the central switchboard for the brain that can easily store short-term memory patterns. However, these patterns have to be encoded in the neocortex to provide space for coding new short-term memories. This complex process of rebuilding the neural network of the brain takes place during sleep. Unlike rest or conservation of energy, this highest feat of evolutionary neural mathematics requires the brain to be shut off entirely from environmental input (in most animals)! This automatic rewiring is the main reason for which we sleep and why there is no conscious processing involved!
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Good sleep, good learning, good life
thematical analysis of spatiotemporal neuronal firing patterns, Buzsáki provided a good model explaining how the two components of sleep, REM and NREM sleep, work together to optimize memories. <span>The hippocampus acts as the central switchboard for the brain that can easily store short-term memory patterns. However, these patterns have to be encoded in the neocortex to provide space for coding new short-term memories. This complex process of rebuilding the neural network of the brain takes place during sleep. Unlike rest or conservation of energy, this highest feat of evolutionary neural mathematics requires the brain to be shut off entirely from environmental input (in most animals)! This automatic rewiring is the main reason for which we sleep and why there is no conscious processing involved! During sleep, the brain works as hard as during SAT or GRE exams. It rewires its circuits to make sure that all newly gained knowledge is optimally stored for future use. We sleep so th




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Disk and RAM metaphor

A metaphor can help understand the role of sleep and why alarm clocks are bad. We can compare the brain and its NREM-REM sleep cycles to an ordinary PC. During the day, while learning and experiencing new things, you store your new data in RAM memory. During the night, while first in NREM, you write the data down to the hard disk. During REM, which follows NREM in the night, you do the disk defragmentation, i.e. you organize data, sort them, build new connections, etc. Overnight, you repeat the write-and-defragment cycle until all RAM data is neatly written to the disk (for long-term use), and your RAM is clear and ready for a new day of learning. Upon waking up, you reboot the computer. If you reboot early with the use of an alarm clock, you often leave your disk fragmented. Your data access is slow, and your thinking is confused. Even worse, some of the data may not even get written to the disk. It is as if you have never stored it in RAM in the first place. In conclusion, if you use an alarm clock, you endanger your data

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omplex set of brain nuclei. Interference with this system disrupts the function of sleep. For more see: Sleep control system For more see: Neural optimization in sleep Not all scientists agree. <span>Disk and RAM metaphor A metaphor can help understand the role of sleep and why alarm clocks are bad. We can compare the brain and its NREM-REM sleep cycles to an ordinary PC. During the day, while learning and experiencing new things, you store your new data in RAM memory. During the night, while first in NREM, you write the data down to the hard disk. During REM, which follows NREM in the night, you do the disk defragmentation, i.e. you organize data, sort them, build new connections, etc. Overnight, you repeat the write-and-defragment cycle until all RAM data is neatly written to the disk (for long-term use), and your RAM is clear and ready for a new day of learning. Upon waking up, you reboot the computer. If you reboot early with the use of an alarm clock, you often leave your disk fragmented. Your data access is slow, and your thinking is confused. Even worse, some of the data may not even get written to the disk. It is as if you have never stored it in RAM in the first place. In conclusion, if you use an alarm clock, you endanger your data. If you do not care about your intellectual performance, you may want to know that there are many other biological reasons for which using alarm clocks is unhealthy. Many people use ala




#Apprentissage #Culture #Learning #Sleep #Sommeil
Poor sleep kills as many people on the roads as alcohol. 1550 annual fatalities in the US can be attributed to drowsy driving. That's nearly an equivalent of six WTC collapse tragedies in a decade! Amazingly, as the pain and suffering is diluted in the population, drowsy driving does not nearly make as many headlines as a terrorist attack. At least a third of Americans have fallen asleep behind the wheel at least once! During the shift to DST in spring, car accidents increase by 9%.
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e in history if he had failed to recover the Spirit of St. Louis from a dive caused by microsleep. Sleep deprivation has changed the future of nuclear fission and the future of oil exploration. <span>Poor sleep kills as many people on the roads as alcohol. 1550 annual fatalities in the US can be attributed to drowsy driving. That's nearly an equivalent of six WTC collapse tragedies in a decade! Amazingly, as the pain and suffering is diluted in the population, drowsy driving does not nearly make as many headlines as a terrorist attack. At least a third of Americans have fallen asleep behind the wheel at least once! During the shift to DST in spring, car accidents increase by 9%. Sleep deprivation carries an astronomical cost to industrialized societies. There are zillions of hours wasted on unproductive learning in schools, and zillions of man-hours wasted on f




#Apprentissage #Culture #Learning #Sleep #Sommeil
In a comment to the conclusion of a sleep deprivation debate organized by the Economist, Karen M. wrote: "We don't get enough sleep, and we are not going to "change our ways" because there are already too few hours in most people's days to do things they enjoy. Call it a sad fact of life because that's what it is". Even though Karen attempted to represent the entire population saying "we", many readers of this article will disagree and do their best to get as much sleep as physiologically necessary. Otherwise my writing effort would not be needed. Good sleep makes us nicer, smarter, and saves lives!
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or the better. We need to respect sleep, let kids sleep, design smarter night-shift schedules, and minimize sleep deprivation in jobs that weigh on life and death (e.g. the medical profession). <span>In a comment to the conclusion of a sleep deprivation debate organized by the Economist, Karen M. wrote: "We don't get enough sleep, and we are not going to "change our ways" because there are already too few hours in most people's days to do things they enjoy. Call it a sad fact of life because that's what it is". Even though Karen attempted to represent the entire population saying "we", many readers of this article will disagree and do their best to get as much sleep as physiologically necessary. Otherwise my writing effort would not be needed. Good sleep makes us nicer, smarter, and saves lives! See: 10 Things to Hate About Sleep Loss from WebMD. If you do not sleep, you die! Nearly everyone has pulled an all nighter once upon a time. Even if this is often an unpleasant experie




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If you do not sleep, you die!

Nearly everyone has pulled an all nighter once upon a time. Even if this is often an unpleasant experience, it nearly always ends up with a 100% recovery after a single night of solid sleep. It is therefore a bit surprising to know that that a week or two of sleep deprivation can result in death! Sleep researchers constructed a cruel contraption that would wake up rats as soon as they fell asleep. This contraptions showed that it takes an average of 3 weeks to kill a rat by sleep deprivation (or some 5 months by REM sleep deprivation alone)(Rechtschaffen 1998[7]). Dr Siegel demonstrated brain damage in sleep-deprived rats (Siegel 2003[8]). Due to an increase in the level of glucocorticoids, neurogenesis in some portions of the brain is inhibited by lack of sleep[9]. In short, sleep deprivation is very bad for the health of the brain.

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Good sleep, good learning, good life
uch sleep as physiologically necessary. Otherwise my writing effort would not be needed. Good sleep makes us nicer, smarter, and saves lives! See: 10 Things to Hate About Sleep Loss from WebMD. <span>If you do not sleep, you die! Nearly everyone has pulled an all nighter once upon a time. Even if this is often an unpleasant experience, it nearly always ends up with a 100% recovery after a single night of solid sleep. It is therefore a bit surprising to know that that a week or two of sleep deprivation can result in death! Sleep researchers constructed a cruel contraption that would wake up rats as soon as they fell asleep. This contraptions showed that it takes an average of 3 weeks to kill a rat by sleep deprivation (or some 5 months by REM sleep deprivation alone)(Rechtschaffen 1998[7]). Dr Siegel demonstrated brain damage in sleep-deprived rats (Siegel 2003[8]). Due to an increase in the level of glucocorticoids, neurogenesis in some portions of the brain is inhibited by lack of sleep[9]. In short, sleep deprivation is very bad for the health of the brain. Sleep deprivation is a well-known form of torture. Yet, for ethical reasons, the rat experiment could not be reproduced in humans (to its ultimate end). However, we have a rough idea as




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However, we have a rough idea as to the degree of human durability in sleep deprived state due to fact that we can study the effects of sleep disorders. One of them is fatal familial insomnia, in which a mutation causes the affected people to suffer from a progressively worsening insomnia that ends in death within a few months. Another example is the Morvan's syndrome in which an autoimmune disease destroys neuronal potassium channels that lead to severe insomnia and death (unless the disease progresses into remission)
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is very bad for the health of the brain. Sleep deprivation is a well-known form of torture. Yet, for ethical reasons, the rat experiment could not be reproduced in humans (to its ultimate end). <span>However, we have a rough idea as to the degree of human durability in sleep deprived state due to fact that we can study the effects of sleep disorders. One of them is fatal familial insomnia, in which a mutation causes the affected people to suffer from a progressively worsening insomnia that ends in death within a few months. Another example is the Morvan's syndrome in which an autoimmune disease destroys neuronal potassium channels that lead to severe insomnia and death (unless the disease progresses into remission). You may have heard of reports of people who do not sleep at all. These are certainly inaccurate or false. Those who report never sleeping are either boasting or experiencing a sleep st




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Brain's garbage collection

Why is sleep deprivation fatal? Death of sleep deprivation is like death of an old age in general. Very often, multiple causes conspire to produce the final inevitable outcome. Probably nobody knows the exact answer to this mystery. However, research into the role of sleep gives us pretty strong hints. One of the most important functions of sleep is the re-organization of neural networks in the brain.

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naccurate or false. Those who report never sleeping are either boasting or experiencing a sleep state misperception that leaves them with an illusion that they do not sleep when resting in bed. <span>Brain's garbage collection Why is sleep deprivation fatal? Death of sleep deprivation is like death of an old age in general. Very often, multiple causes conspire to produce the final inevitable outcome. Probably nobody knows the exact answer to this mystery. However, research into the role of sleep gives us pretty strong hints. One of the most important functions of sleep is the re-organization of neural networks in the brain. During the day, we learn new things, memorize, acquire skills, figure things out, set new memories through creative associations, etc. After a long day of waking, the brain is full of d




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This neural role of sleep is so fundamental that sleep deprivation affects nearly all functions of the body that are governed by the nervous system. Without a regular garbage collection, individual networks begin to malfunction. These initially minor malfunctions can add up to a serious problem for the entire organism. Most prominent effects of sleep deprivation are problems with thermoregulation, decline in immune function, hormonal changes (e.g. increase in glucocorticoids and catecholamines), metabolic changes[link: Sleep and Glucose metabolism], malnutrition, hallucinations, autonomic system malfunction, changes in cell adhesion, increase in inflammatory factors (e.g. IL-6, TNF, C-reactive protein, etc.), skin lesions, oxidative stress, DNA damage, etc.
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ion that need to be integrated with things we have learned earlier in life. Without this re-organization, the brain would harbor chaos, and would quickly run out of space to store new memories. <span>This neural role of sleep is so fundamental that sleep deprivation affects nearly all functions of the body that are governed by the nervous system. Without a regular garbage collection, individual networks begin to malfunction. These initially minor malfunctions can add up to a serious problem for the entire organism. Most prominent effects of sleep deprivation are problems with thermoregulation, decline in immune function, hormonal changes (e.g. increase in glucocorticoids and catecholamines), metabolic changes[link: Sleep and Glucose metabolism], malnutrition, hallucinations, autonomic system malfunction, changes in cell adhesion, increase in inflammatory factors (e.g. IL-6, TNF, C-reactive protein, etc.), skin lesions, oxidative stress, DNA damage, etc. Those problems become serious enough to kill. Metaphorically speaking, if we compared a less developed organism to a WW1 bomber, we could imagine that the process of evolving into a hum




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Sleep protection

There is a second layer of trouble in sleep deprivation. Due to the importance of sleep, all advanced organisms implement a sleep protection program. This program ensures that sleep deprivation results in unpleasant symptoms. It also produces a remarkably powerful sleep drive that is very hard to overcome. Staying awake becomes unbearable. Closing one's eyes becomes one of the most soothing things in the universe. Are these symptoms a result of network malfunction? Definitely not.

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reliance on advanced software or neural function is always dangerous! Luckily, all we need to eliminate the danger is to just go to sleep every day. For more see: Neural optimization in sleep. <span>Sleep protection There is a second layer of trouble in sleep deprivation. Due to the importance of sleep, all advanced organisms implement a sleep protection program. This program ensures that sleep deprivation results in unpleasant symptoms. It also produces a remarkably powerful sleep drive that is very hard to overcome. Staying awake becomes unbearable. Closing one's eyes becomes one of the most soothing things in the universe. Are these symptoms a result of network malfunction? Definitely not. If they were, the drive to sleep might malfunction as well. Moreover, recovery from sleep deprivation would not be as fast, as easy, and as complete! Sleep protection program is there,




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Sleep protection program is there, and it can make the effects of sleep deprivation worse. Like a cytokine storm in an overzealous immune system, sleep protection program can potentially add to the damage caused by the network malfunction in sleep deprivation.

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ult of network malfunction? Definitely not. If they were, the drive to sleep might malfunction as well. Moreover, recovery from sleep deprivation would not be as fast, as easy, and as complete! <span>Sleep protection program is there, and it can make the effects of sleep deprivation worse. Like a cytokine storm in an overzealous immune system, sleep protection program can potentially add to the damage caused by the network malfunction in sleep deprivation. Anabolic sleep Last but not least, sleep has evolved to become a chief anabolic state of the organism. Without it, the body keeps using itself up, without much time to rebuild. Turning




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Anabolic sleep

Last but not least, sleep has evolved to become a chief anabolic state of the organism. Without it, the body keeps using itself up, without much time to rebuild. Turning on anabolic state does not require turning off the consciousness, however, the time of night rest seems to be the best time for the body to do all the rebuilding. As we must sleep anyway, that anabolic functions became consolidated with other functions of sleep, and now may be indispensable

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leep deprivation worse. Like a cytokine storm in an overzealous immune system, sleep protection program can potentially add to the damage caused by the network malfunction in sleep deprivation. <span>Anabolic sleep Last but not least, sleep has evolved to become a chief anabolic state of the organism. Without it, the body keeps using itself up, without much time to rebuild. Turning on anabolic state does not require turning off the consciousness, however, the time of night rest seems to be the best time for the body to do all the rebuilding. As we must sleep anyway, that anabolic functions became consolidated with other functions of sleep, and now may be indispensable. The anabolic state, and the nighttime increase in GH or testosterone, also affects the neural networks and the status of our "mind software". Hormonal changes stimulate and/or inhibit




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The anabolic state, and the nighttime increase in GH or testosterone, also affects the neural networks and the status of our "mind software". Hormonal changes stimulate and/or inhibit neural growth. Dr Michael Stryker, best known for demonstrating the role of sleep in brain development (Stryker et al. 2001[10]), says that nighttime hormonal changes may "play a crucial role in consolidating and enhancing waking experience"[11].
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eems to be the best time for the body to do all the rebuilding. As we must sleep anyway, that anabolic functions became consolidated with other functions of sleep, and now may be indispensable. <span>The anabolic state, and the nighttime increase in GH or testosterone, also affects the neural networks and the status of our "mind software". Hormonal changes stimulate and/or inhibit neural growth. Dr Michael Stryker, best known for demonstrating the role of sleep in brain development (Stryker et al. 2001[10]), says that nighttime hormonal changes may "play a crucial role in consolidating and enhancing waking experience"[11]. One of the leading causes of death in sleep deprivation seems to have been opportunistic bacterial infections caused by a decline in the immune function (e.g. no febrile response). That




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One of the leading causes of death in sleep deprivation seems to have been opportunistic bacterial infections caused by a decline in the immune function (e.g. no febrile response). That decline could be caused equally well by (a) poor neural control of the immune function or (b) straight effect of hypercatabolism. Whatever the cause, scientists have quickly figured out that application of antibiotics did not help much in preventing death from those infections. Sleep deprived rats would die anyway. The infection might speed up death that was otherwise inevitable.
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Good sleep, good learning, good life
onstrating the role of sleep in brain development (Stryker et al. 2001[10]), says that nighttime hormonal changes may "play a crucial role in consolidating and enhancing waking experience"[11]. <span>One of the leading causes of death in sleep deprivation seems to have been opportunistic bacterial infections caused by a decline in the immune function (e.g. no febrile response). That decline could be caused equally well by (a) poor neural control of the immune function or (b) straight effect of hypercatabolism. Whatever the cause, scientists have quickly figured out that application of antibiotics did not help much in preventing death from those infections. Sleep deprived rats would die anyway. The infection might speed up death that was otherwise inevitable. Why do we die without sleep? It is impossible to quantify the contribution of those three factors to the fatal outcome of prolonged sleep deprivation: network malfunction, or secondary




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Two components of sleep

Electric lighting and stress are the two chief culprits that have converted the natural process of sleep into a daily struggle for millions. In the new millennium, we can rarely hope to get a good night sleep without understanding the science and the art of sleep. Currently, the societal understanding of sleep and its functions is as dismal as the understanding of the health risks of cigarettes in the 1920s. A majority of the population inflict pain, misery and mental torture on themselves and their children by trying to regulate their sleep with alarm clocks, irrational shift-work patterns, sleeping pills, alcohol, caffeine, etc.

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Good sleep, good learning, good life
race the blessings of healthy unrestrained sleep. After all, there are few better things in life than a good night sleep after a well-spent day. Sleep should be listed among basic human rights! <span>Two components of sleep Electric lighting and stress are the two chief culprits that have converted the natural process of sleep into a daily struggle for millions. In the new millennium, we can rarely hope to get a good night sleep without understanding the science and the art of sleep. Currently, the societal understanding of sleep and its functions is as dismal as the understanding of the health risks of cigarettes in the 1920s. A majority of the population inflict pain, misery and mental torture on themselves and their children by trying to regulate their sleep with alarm clocks, irrational shift-work patterns, sleeping pills, alcohol, caffeine, etc. For a chance to break out from unhealthy sleep habits, you need to understand the two-component model of sleep regulation. There are two components of sleepiness that drive you to bed:




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There are two components of sleepiness that drive you to bed:

  • circadian component - sleepiness comes back to us in cycles which are usually about one day long
  • homeostatic component - sleepiness increases with the length of time we stay awake

Only a combination of these two components determines the optimum time for sleep. Most importantly, you should remember that even strong sleepiness resulting from the homeostatic component may not be sufficient to get good sleep if the timing goes against the greatest sleep propensity determined by the circadian component

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Good sleep, good learning, good life
rrational shift-work patterns, sleeping pills, alcohol, caffeine, etc. For a chance to break out from unhealthy sleep habits, you need to understand the two-component model of sleep regulation. <span>There are two components of sleepiness that drive you to bed: circadian component - sleepiness comes back to us in cycles which are usually about one day long homeostatic component - sleepiness increases with the length of time we stay awake Only a combination of these two components determines the optimum time for sleep. Most importantly, you should remember that even strong sleepiness resulting from the homeostatic component may not be sufficient to get good sleep if the timing goes against the greatest sleep propensity determined by the circadian component. Circadian component There are around hundred known body functions that oscillate between maximum and minimum values in a day-long cycle. Because these functions take about a day's time




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Circadian component

There are around hundred known body functions that oscillate between maximum and minimum values in a day-long cycle. Because these functions take about a day's time to complete, the term circadian rhythm was coined by Dr Franz Halberg of Germany in 1959 (in Latin circadian means about a day). The overall tendency to maintain sleep is also subject to such a circadian rhythm. In an average case, the maximum sleepiness comes in the middle of the night, reaches the minimum at awakening, and again increases slightly at siesta time in the afternoon. However, the circadian sleepiness is often shifted in phase as compared with your desired sleep time. Consequently, if your maximum sleepiness comes in the morning, you may find it difficult to fall asleep late in the evening, even if you missed a lot of sleep on the preceding day. In other words, the optimum timing of your sleep should take into consideration your circadian rhythm.

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Good sleep, good learning, good life
trong sleepiness resulting from the homeostatic component may not be sufficient to get good sleep if the timing goes against the greatest sleep propensity determined by the circadian component. <span>Circadian component There are around hundred known body functions that oscillate between maximum and minimum values in a day-long cycle. Because these functions take about a day's time to complete, the term circadian rhythm was coined by Dr Franz Halberg of Germany in 1959 (in Latin circadian means about a day). The overall tendency to maintain sleep is also subject to such a circadian rhythm. In an average case, the maximum sleepiness comes in the middle of the night, reaches the minimum at awakening, and again increases slightly at siesta time in the afternoon. However, the circadian sleepiness is often shifted in phase as compared with your desired sleep time. Consequently, if your maximum sleepiness comes in the morning, you may find it difficult to fall asleep late in the evening, even if you missed a lot of sleep on the preceding day. In other words, the optimum timing of your sleep should take into consideration your circadian rhythm. Homeostatic component Homeostasis is the term that refers to maintaining equilibrium or balance in physiological and metabolic functions. If you drink liquids containing lots of calcium




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Homeostatic component

Homeostasis is the term that refers to maintaining equilibrium or balance in physiological and metabolic functions. If you drink liquids containing lots of calcium, homeostatic mechanisms will make sure that you excrete calcium with urine or deposit it in the bones. This is used to make sure your blood levels of calcium remain the same. Similar mechanisms are used to regulate overall sleepiness and its multiple subcomponents. The longer you stay awake, the more you learn, the more you think, the higher your tendency to fall asleep. On the other hand, caffeine, stress, exercise and other factors may temporarily reduce your homeostatic sleepiness. The homeostatic mechanism prepares you for sleep after a long day of intellectual work. At the same time it prevents you from falling asleep in emergencies.

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o fall asleep late in the evening, even if you missed a lot of sleep on the preceding day. In other words, the optimum timing of your sleep should take into consideration your circadian rhythm. <span>Homeostatic component Homeostasis is the term that refers to maintaining equilibrium or balance in physiological and metabolic functions. If you drink liquids containing lots of calcium, homeostatic mechanisms will make sure that you excrete calcium with urine or deposit it in the bones. This is used to make sure your blood levels of calcium remain the same. Similar mechanisms are used to regulate overall sleepiness and its multiple subcomponents. The longer you stay awake, the more you learn, the more you think, the higher your tendency to fall asleep. On the other hand, caffeine, stress, exercise and other factors may temporarily reduce your homeostatic sleepiness. The homeostatic mechanism prepares you for sleep after a long day of intellectual work. At the same time it prevents you from falling asleep in emergencies. Clock and Hourglass metaphor A metaphor is useful in explaining the two components of sleep (for a more scientific explanation see: Borbely model). Deep in the brain, your body clock is




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It is important to know that sleepy potion produced by the body clock is not enough to put you to sleep. The brain also uses the hourglass of mental energy that gives you some time every day that you can devote to intellectual work. When you wake up, the hourglass is full and starts being emptied. With every waking moment, with everything your brain absorbs, with every mental effort, the hourglass is less and less full. Only when the hourglass of mental energy is empty will you able to quickly fall asleep.

To get a good night sleep, you need to combine two factors:

  • your body clock must be saying "time to sleep" (circadian component of sleep)
  • your hourglass of power must be saying "no more mental work" (homeostatic component of sleep)
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Good sleep, good learning, good life
they go to sleep too early, before they get their fix of sleepy potion, they will toss and turn. Often for hours. You need to listen to your body clock to know the right moment to go to sleep. <span>It is important to know that sleepy potion produced by the body clock is not enough to put you to sleep. The brain also uses the hourglass of mental energy that gives you some time every day that you can devote to intellectual work. When you wake up, the hourglass is full and starts being emptied. With every waking moment, with everything your brain absorbs, with every mental effort, the hourglass is less and less full. Only when the hourglass of mental energy is empty will you able to quickly fall asleep. To get a good night sleep, you need to combine two factors: your body clock must be saying "time to sleep" (circadian component of sleep) your hourglass of power must be saying "no more mental work" (homeostatic component of sleep) If your sleepy potion tries to put you to sleep but your hourglass of mental energy is full, you will be very groggy, tired, but you will not fall asleep. If, on the other hand, you try




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If your sleepy potion tries to put you to sleep but your hourglass of mental energy is full, you will be very groggy, tired, but you will not fall asleep. If, on the other hand, you try to sleep without the sleepy potion while the hourglass of power is empty, you may succeed, but you will wake up very fast with your hourglass full again. That will make sleeping again nearly impossible. Insomniacs go to sleep before the body clock releases the sleepy potion. When you wake up early with an alarm clock, you can hardly get to your feet because your body is full of sleepy potion, which begs you to go back to sleep. When you are drowsy in the afternoon, your hourglass of mental power might be almost empty. A quick nap will then help you fill it up again and be very productive in the evening. If you drink coffee in the morning, it helps you charge the hourglass and add some extra mental energy. But coffee combined with the sleepy potion produces a poisonous mix that engulfs your brain in sickly miasma. If you try to drink coffee to stay up in the night, you will feel like a horse kicked you in the stomach. That's the acme of a criminal attack on your brain's health
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Good sleep, good learning, good life
combine two factors: your body clock must be saying "time to sleep" (circadian component of sleep) your hourglass of power must be saying "no more mental work" (homeostatic component of sleep) <span>If your sleepy potion tries to put you to sleep but your hourglass of mental energy is full, you will be very groggy, tired, but you will not fall asleep. If, on the other hand, you try to sleep without the sleepy potion while the hourglass of power is empty, you may succeed, but you will wake up very fast with your hourglass full again. That will make sleeping again nearly impossible. Insomniacs go to sleep before the body clock releases the sleepy potion. When you wake up early with an alarm clock, you can hardly get to your feet because your body is full of sleepy potion, which begs you to go back to sleep. When you are drowsy in the afternoon, your hourglass of mental power might be almost empty. A quick nap will then help you fill it up again and be very productive in the evening. If you drink coffee in the morning, it helps you charge the hourglass and add some extra mental energy. But coffee combined with the sleepy potion produces a poisonous mix that engulfs your brain in sickly miasma. If you try to drink coffee to stay up in the night, you will feel like a horse kicked you in the stomach. That's the acme of a criminal attack on your brain's health. The fundamental theorem of good sleep Let us now formulate the fundamental theorem of good sleep: To get high quality night sleep that maximizes your learning effects your sleep start




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To get high quality night sleep that maximizes your learning effects your sleep start time should meet these two criteria:
  • strong homeostatic sleepiness: this usually means going to sleep not earlier than 15-19 hours after awakening from the previous night sleep
  • ascending circadian sleepiness: this means going to sleep at a time of day when you usually experience a rapid increase in drowsiness. Not earlier and not later! Knowing the timing of your circadian rhythm is critical for good night sleep
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Good sleep, good learning, good life
a horse kicked you in the stomach. That's the acme of a criminal attack on your brain's health. The fundamental theorem of good sleep Let us now formulate the fundamental theorem of good sleep: <span>To get high quality night sleep that maximizes your learning effects your sleep start time should meet these two criteria: strong homeostatic sleepiness: this usually means going to sleep not earlier than 15-19 hours after awakening from the previous night sleep ascending circadian sleepiness: this means going to sleep at a time of day when you usually experience a rapid increase in drowsiness. Not earlier and not later! Knowing the timing of your circadian rhythm is critical for good night sleep You should be aware that using the circadian component will only work when all its physiological subcomponents run in sync (as it is the case in free running sleep). People with irregul




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You should be aware that using the circadian component will only work when all its physiological subcomponents run in sync (as it is the case in free running sleep). People with irregular sleep hours and highly stressful lives may simply be unable to locate the point of ascending circadian sleepiness as this point may not exist!
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Good sleep, good learning, good life
ing to sleep at a time of day when you usually experience a rapid increase in drowsiness. Not earlier and not later! Knowing the timing of your circadian rhythm is critical for good night sleep <span>You should be aware that using the circadian component will only work when all its physiological subcomponents run in sync (as it is the case in free running sleep). People with irregular sleep hours and highly stressful lives may simply be unable to locate the point of ascending circadian sleepiness as this point may not exist! For a visual illustration of circadian and homeostatic components, see section Two-component sleep model in SuperMemo. For more on the two components of sleep see: Borbely model. When g




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When good sleep might not come?

You may be surprised to find out that your internal circadian oscillation is based on a period that is closer to 25 hours than to 24 hours! To be exact, it varies between individuals, seasons, and other daily factors such as stress, timing of sleep, timing of the light period, intensity of light, exercise, and many more. Usually it falls into the range from 24.5 hours to 25.5 hours.

Most of us are able to entrain this 25 circadian rhythm into a 24-hour cycle by using factors that reset the oscillation. These factors include intense morning light, work, exercise, etc. German scientists have named these factors zeitgebers (i.e. factors that give time). As a result of the influence of zeitgebers, in a well-adjusted individual, the cycle can be set back by 30-60 minutes each day. However, the entrainment to the 24-hour cycle may come with difficulty to many individuals due to factors such as:

  • blindness (i.e. the inability to use the main zeitgeber: light)
  • short-sightedness (i.e. reduced sensitivity to light zeitgeber)
  • increased demand for sleep (e.g. as a result of intense learning, highly creative job position, exercise, etc.)
  • stress
  • endocrine disorders
  • sleep disorders
  • adolescence
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Good sleep, good learning, good life
may not exist! For a visual illustration of circadian and homeostatic components, see section Two-component sleep model in SuperMemo. For more on the two components of sleep see: Borbely model. <span>When good sleep might not come? You may be surprised to find out that your internal circadian oscillation is based on a period that is closer to 25 hours than to 24 hours! To be exact, it varies between individuals, seasons, and other daily factors such as stress, timing of sleep, timing of the light period, intensity of light, exercise, and many more. Usually it falls into the range from 24.5 hours to 25.5 hours. Most of us are able to entrain this 25 circadian rhythm into a 24-hour cycle by using factors that reset the oscillation. These factors include intense morning light, work, exercise, etc. German scientists have named these factors zeitgebers (i.e. factors that give time). As a result of the influence of zeitgebers, in a well-adjusted individual, the cycle can be set back by 30-60 minutes each day. However, the entrainment to the 24-hour cycle may come with difficulty to many individuals due to factors such as: blindness (i.e. the inability to use the main zeitgeber: light) short-sightedness (i.e. reduced sensitivity to light zeitgeber) increased demand for sleep (e.g. as a result of intense learning, highly creative job position, exercise, etc.) stress endocrine disorders sleep disorders adolescence A great deal of sleep disorders can be explained by entrainment failure (i.e. the failure to reset the 25-hour circadian rhythm to the 24-hour daylight cycle). In other words, in the in




#Apprentissage #Culture #Learning #Sleep #Sommeil
A great deal of sleep disorders can be explained by entrainment failure (i.e. the failure to reset the 25-hour circadian rhythm to the 24-hour daylight cycle). In other words, in the interdependence between sleep disorders and entrainment failure, the cause-effect relationship will often be reversed! Due to the physiological function of sleep, which is the rewiring of the neural networks of the brain, we can naturally expect that the demand for sleep be associated with the amount of learning on the preceding days. This link may also explain a decreased demand for sleep in retirement due to a decrease in intellectual activity. This age-related drop in the demand for sleep is less likely to be observed in highly active individuals. For similar reasons, the entrainment failure can often be found among students during exams. It is not clear how much of this failure can be attributed to stress, or to the desire to do more on a given day, or to the actual increase in the demand for sleep.
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Good sleep, good learning, good life
tivity to light zeitgeber) increased demand for sleep (e.g. as a result of intense learning, highly creative job position, exercise, etc.) stress endocrine disorders sleep disorders adolescence <span>A great deal of sleep disorders can be explained by entrainment failure (i.e. the failure to reset the 25-hour circadian rhythm to the 24-hour daylight cycle). In other words, in the interdependence between sleep disorders and entrainment failure, the cause-effect relationship will often be reversed! Due to the physiological function of sleep, which is the rewiring of the neural networks of the brain, we can naturally expect that the demand for sleep be associated with the amount of learning on the preceding days. This link may also explain a decreased demand for sleep in retirement due to a decrease in intellectual activity. This age-related drop in the demand for sleep is less likely to be observed in highly active individuals. For similar reasons, the entrainment failure can often be found among students during exams. It is not clear how much of this failure can be attributed to stress, or to the desire to do more on a given day, or to the actual increase in the demand for sleep. Formula for good sleep There is a little-publicized formula that acts as a perfect cure for people who experience continual or seasonal problems with sleep entrainment. This formula is




Article 4822666448140

Aronis et al. 2017: A Bayesian system to detect and characterize overlapping outbreaks
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A Bayesian system to detect and characterize overlapping outbreaks Author links open overlay panelJohn M.Aronisa Nicholas E.MillettaMichael M.WagnerabFuchiangTsuiabYeYeabJeffrey P.FerrarocdPeter J.HaugcdPer H.GestelandcdeGregory F.Cooperab https://doi.org/10.1016/j.jbi.2017.08.003Get rights and content Under an Elsevier user license open archive Highlights • We describe a system to model and predict multiple overlapping outbreaks of influenza. • Clinical findings are extracted from patient-care reports using natural language processing. • Disease likelihoods are passed to a multiple outbreak detection system. • The system can recognize and characterize overlapping outbreaks of influenza. Abstract Outbreaks of infectious diseases such as influenza are a significant threat to human health. Because there are different strains of influ



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This paper (Aronis et al. 2017) describes a Multiple Outbreak Detection System (MODS) that detects and characterizes overlapping outbreaks of influenza. MODS is part of a framework for disease surveillance developed by our group [3], [4], [5]. In this framework, a natural language processing system extracts signs and symptoms from the full text of emergency department (ED) patient care reports. These extracted features are combined with laboratory values and passed to a Case Detection System (CDS) that infers a probability distribution over the diseases each patient may have. For each patient, this distribution is expressed as a set of likelihoods of the patient’s data. MODS searches a space of outbreak models and scores each model according to the probability of the findings of each patient in the ED given the model. Models are weighted and combined to make predictions. See Fig. 1.

  1. Download : Download high-res image (39KB)
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Fig. 1. End-to-end framework for outbreak detection and characterization.

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A Bayesian system to detect and characterize overlapping outbreaks
onsiderable health care costs and lost productivity [1]. There is a clear need for accurate, timely predictions of influenza outbreaks for hospitals, public health officials , and business [2]. <span>This paper describes a Multiple Outbreak Detection System (MODS) that detects and characterizes overlapping outbreaks of influenza. MODS is part of a framework for disease surveillance developed by our group [3], [4], [5]. In this framework, a natural language processing system extracts signs and symptoms from the full text of emergency department (ED) patient care reports. These extracted features are combined with laboratory values and passed to a Case Detection System (CDS) that infers a probability distribution over the diseases each patient may have. For each patient, this distribution is expressed as a set of likelihoods of the patient’s data. MODS searches a space of outbreak models and scores each model according to the probability of the findings of each patient in the ED given the model. Models are weighted and combined to make predictions. See Fig. 1. Download : Download high-res image (39KB) Download : Download full-size image Fig. 1. End-to-end framework for outbreak detection and characterization. There has been significant prior work in the detection and characterization of outbreaks of influenza [6], [7], [8], [9], [10]. The work reported here differs from much of the prior wor




The work (Aronis et al. 2017) reported here differs from much of the prior work in three important ways. First, we address the problem of detecting and characterizing multiple, overlapping outbreaks. These are commonly due to separate type A and type B infections, but may also be caused by multiple introductions of the same influenza strain, the spread of an influenza strain in different demographic groups, or different strains of influenza [1], [11], [12], [13], [14]. Second, we do not rely on simple counts. Instead, for each patient, CDS produces a set of likelihoods of that patient’s evidence given the diseases he or she may have. This is more robust than a posterior probability. While the posterior probability of influenza given fever and cough in a particular patient will change if it is summer, the peak of an influenza outbreak, or the days following an anthrax attack [15], the likelihood of fever and cough given influenza is relatively stable. Finally, we explicitly account for Non-Influenza Influenza-Like Illnesses (NI-ILI) which are clinically similar to influenza and can also display outbreak activity.
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A Bayesian system to detect and characterize overlapping outbreaks
End-to-end framework for outbreak detection and characterization. There has been significant prior work in the detection and characterization of outbreaks of influenza [6], [7], [8], [9], [10]. <span>The work reported here differs from much of the prior work in three important ways. First, we address the problem of detecting and characterizing multiple, overlapping outbreaks. These are commonly due to separate type A and type B infections, but may also be caused by multiple introductions of the same influenza strain, the spread of an influenza strain in different demographic groups, or different strains of influenza [1], [11], [12], [13], [14]. Second, we do not rely on simple counts. Instead, for each patient, CDS produces a set of likelihoods of that patient’s evidence given the diseases he or she may have. This is more robust than a posterior probability . While the posterior probability of influenza given fever and cough in a particular patient will change if it is summer, the peak of an influenza outbreak, or the days following an anthrax attack [15], the likelihood of fever and cough given influenza is relatively stable. Finally, we explicitly account for Non-Influenza Influenza-Like Illnesses (NI-ILI) which are clinically similar to influenza and can also display outbreak activity. 2. Material and methods 2.1. Evidence As stated above, MODS is part of an end-to-end system that starts with the full text of emergency department patient care reports. These reports co




Positive influenza A tests peaked around January 1 and positive influenza B tests peaked around February 26 [20]. These dates are close to the peaks predicted by MODS as shown in Fig. 8. This is noteworthy given that MODS did not have test information that distinguished A from B, but was able to recognize separate A and B outbreaks.
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A Bayesian system to detect and characterize overlapping outbreaks
rk [4]. The double peak predicted by MODS from the Salt Lake City 2010–2011 data is intriguing. The Utah Public Health Laboratory tracks positive influenza laboratory tests broken down by type. <span>Positive influenza A tests peaked around January 1 and positive influenza B tests peaked around February 26 [20]. These dates are close to the peaks predicted by MODS as shown in Fig. 8. This is noteworthy given that MODS did not have test information that distinguished A from B, but was able to recognize separate A and B outbreaks. Table 5. Results of evaluation on 100 simulated single outbreaks. Fraction of Outbreak Cases That Have Occurred Mean Number of Days Until Peak Mean Posterior Probability an Outbreak is




We assume there is a constant, baseline number of influenza cases, b, in the general population throughout the year. We derive this number using data from summer months. However, the baseline varies daily and throughout the year. We could avoid this assumption by integrating over the range of values of b in Eqs. (14), (15) each day. However, we do not believe this will affect the results since the baseline level is very small compared to outbreak levels.
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A Bayesian system to detect and characterize overlapping outbreaks
State Laboratory: Public Health.) 4.2. Limitations The work reported here has several limitations. These stem from our basic assumptions, our use of SEIR models, and computational limitations. <span>We assume there is a constant, baseline number of influenza cases, b, in the general population throughout the year. We derive this number using data from summer months. However, the baseline varies daily and throughout the year. We could avoid this assumption by integrating over the range of values of b in Eqs. (14), (15) each day. However, we do not believe this will affect the results since the baseline level is very small compared to outbreak levels. We assume that the basic context of an outbreak remains fixed for its duration. However, in reality, weather and humidity, immunization programs, and shifting populations can affect how




We assume that the basic context of an outbreak remains fixed for its duration. However, in reality, weather and humidity, immunization programs, and shifting populations can affect how an outbreak proceeds [21]. These concerns can be addressed by allowing the basic parameters of models to change over time.
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A Bayesian system to detect and characterize overlapping outbreaks
ntegrating over the range of values of b in Eqs. (14), (15) each day. However, we do not believe this will affect the results since the baseline level is very small compared to outbreak levels. <span>We assume that the basic context of an outbreak remains fixed for its duration. However, in reality, weather and humidity, immunization programs, and shifting populations can affect how an outbreak proceeds [21]. These concerns can be addressed by allowing the basic parameters of models to change over time. We also assume that θ (the probability that a person in the general population who has influenza will go to an ED) is constant throughout the outbreak. In fact, it can change daily base




assume that θ (the probability that a person in the general population who has influenza will go to an ED) is constant throughout the outbreak. In fact, it can change daily based on several factors, such as media reports. We can address this by integrating over a range of values for θ each day in Eq. (4) instead of just once over the entire outbreak period (essentially by moving the integral to after the daily product). However, we would want to model some dependency in θ from one day to the next.
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A Bayesian system to detect and characterize overlapping outbreaks
immunization programs, and shifting populations can affect how an outbreak proceeds [21]. These concerns can be addressed by allowing the basic parameters of models to change over time. We also <span>assume that θ (the probability that a person in the general population who has influenza will go to an ED) is constant throughout the outbreak. In fact, it can change daily based on several factors, such as media reports. We can address this by integrating over a range of values for θ each day in Eq. (4) instead of just once over the entire outbreak period (essentially by moving the integral to after the daily product). However, we would want to model some dependency in θ from one day to the next. We rely on the mass action principle that any two individuals in the population are equally likely to come in contact with each other. Although this is a common simplifying assumption,




We rely on the mass action principle that any two individuals in the population are equally likely to come in contact with each other. Although this is a common simplifying assumption, it ignores the fact that children are more likely to contact other children in the classroom and adults are more likely to contact adults at work. We can address this assumption by using stratified models
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A Bayesian system to detect and characterize overlapping outbreaks
tead of just once over the entire outbreak period (essentially by moving the integral to after the daily product). However, we would want to model some dependency in θ from one day to the next. <span>We rely on the mass action principle that any two individuals in the population are equally likely to come in contact with each other. Although this is a common simplifying assumption, it ignores the fact that children are more likely to contact other children in the classroom and adults are more likely to contact adults at work. We can address this assumption by using stratified models [17] that maintain separate compartments for different demographic groups. More generally, since our framework only relies on specifying a model of influenza by a set of numeric paramet




when public health officials are faced with an outbreak they often commit to a model they believe best describes the outbreak and design an intervention based on it [11], [12], [24], [25]
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A Bayesian system to detect and characterize overlapping outbreaks
probability to each of them, then computes the expected trajectory of an outbreak based on a combination of the probabilities and predictions of all of the models. It is noncommittal. However, <span>when public health officials are faced with an outbreak they often commit to a model they believe best describes the outbreak and design an intervention based on it [11], [12], [24], [25]. This is fraught with danger since they must make a decision with huge public health, economic, and political risk based on limited evidence early in an outbreak [2]. We propose a diffe




We (Aronis et al. 2017) propose a different approach: instead of picking a single outbreak model, use all of the models, project the effect of an intervention against each model in the set, and predict the interventions’ efficacy with the expected outcome based on the models’ probabilities that were computed before the intervention.
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A Bayesian system to detect and characterize overlapping outbreaks
it [11], [12], [24], [25]. This is fraught with danger since they must make a decision with huge public health, economic, and political risk based on limited evidence early in an outbreak [2]. <span>We propose a different approach: instead of picking a single outbreak model, use all of the models, project the effect of an intervention against each model in the set, and predict the interventions’ efficacy with the expected outcome based on the models’ probabilities that were computed before the intervention. 5. Conclusions We described a framework for the detection and characterization of multiple, overlapping outbreaks of influenza from ED patient care reports. We also described the implem




#155 #Cours #Facultaires #Médecine #Pédiatrie #Tuberculose
L'infection tuberculeuse se définit par une multiplication bacillaire induisant une réponse immunitaire spécifique. La positivité d'un test immunitaire (intradermoréaction à la tuberculine [IDR] ou test in vitro mesurant la libération de l'interféron gamma) en est la marque
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#155 #Cours #Facultaires #Médecine #Pédiatrie #Tuberculose
L'infection tuberculeuse latente est une infection au cours de laquelle la multiplication bacillaire est contrôlée efficacement par la réponse immunitaire spécifique : il n'y a ni signe radiologique ni signe clinique. La tuberculose-maladie est une infection au cours de laquelle la multiplication bacillaire se poursuit malgré la réponse immunitaire spécifique, aboutissant à des signes radiologiques, accompagnés ou non de signes cliniques. Le risque de progression immédiate de l'infection tuberculeuse vers la tuberculose-maladie est majoré chez les enfants âgés de moins de 5 ans (surtout ceux de moins de 2 ans), ainsi que chez les immunodéprimés.
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#155 #Cours #Facultaires #Médecine #Pédiatrie #Tuberculose
Concernant l'enfant, il est estimé qu'environ 1 million d'enfants sont atteints de tuberculose chaque année dans le monde, occasionnant plus de 200 000 décès. Il est également estimé que, chaque année, 10 millions d'enfants deviennent orphelins à cause du décès d'un des deux parents par tuberculose
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The text of each patient care report is parsed to extract 79 findings (such as abdominal pain, cough, and fever) that were deemed by experts to be relevant to the diagnosis of influenza and influenza-like illnesses. Thus, each report is converted into a set of 79 features. Each feature can take the values present (the corresponding finding is explicitly mentioned, e.g. “the patient is cyanotic.”), absent (the finding is denied, e.g. “the patient denies chest pain.”), or missing (the finding is not mentioned in the text). Four pre-coded features, age, respiratory panel ordered, laboratory result available, and laboratory positive influenza are then added to the text-based 79 findings. Thus, each report is converted to a set of 83 features.
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A Bayesian system to detect and characterize overlapping outbreaks
aks of influenza, these can be more informative than just chief complaints [16]. In this section, we describe how these reports are processed to support outbreak detection and characterization. <span>The text of each patient care report is parsed to extract 79 findings (such as abdominal pain, cough, and fever) that were deemed by experts to be relevant to the diagnosis of influenza and influenza-like illnesses . Thus, each report is converted into a set of 79 features. Each feature can take the values present (the corresponding finding is explicitly mentioned, e.g. “the patient is cyanotic.”), absent (the finding is denied, e.g. “the patient denies chest pain .”), or missing (the finding is not mentioned in the text). Four pre-coded features, age, respiratory panel ordered, laboratory result available, and laboratory positive influenza are then added to the text-based 79 findings. Thus, each report is converted to a set of 83 features. These features are listed in Table 1. Table 1. Features extracted from reports with NLP plus precoded findings. Precoded findings are in italics. “AC” or “SLC” indicate if finding was u




#155 #Cours #Facultaires #Médecine #Pédiatrie #Tuberculose

  • En France, il y a environ 5 000 nouveaux cas de tuberculose-maladie chaque année.
    L'incidence en 2015 était de 7,1/100 000.
    Plus du tiers des nouveaux cas sont déclarés en Ile-de-France. Moins de 100 souches bacillaires identifiées chaque année sont MDR.

  • Les cas pédiatriques (< 15 ans) représentent environ 5 % des cas déclarés (autour de 250 cas annuels), la moitié de ces cas étant observée chez l'enfant de moins de 5 ans.
  • Chaque année, 2 à 3 cas de méningite tuberculeuse sont déclarés chez l'enfant de moins de 5 ans.
  • Depuis l'arrêt de l'obligation vaccinale par le BCG au niveau national, on observe une légère augmentation des cas de tuberculose-maladie chez les enfants non vaccinés.
    Cette augmentation reste toutefois bien inférieure aux simulations qui avaient précédé les modifications du calendrier vaccinal
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A Bayesian network (G,P) by definition is a DAG G, and joint probability distribution P that together satisfy the Markov condition.
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Bayesian Networks - an overview | ScienceDirect Topics
Set alert About this page Bayesian Networks Richard E. Neapolitan, Xia Jiang, in Probabilistic Methods for Financial and Marketing Informatics , 2007 3.2.2 Representation of a Bayesian Network <span>A Bayesian network (G,P) by definition is a DAG G, and joint probability distribution P that together satisfy the Markov condition. Then why in Figures 3.1 and 3.2 do we show a Bayesian network as a DAG and a set of conditional probability distributions? The reason is that (G,P) satisfies the Markov condition if and




[unknown IMAGE 4822728314124] #155 #Cours #Facultaires #Médecine #Pédiatrie #Tuberculose #has-images

Enfin, certains enfants vont avoir un risque augmenté de progression immédiate vers la tuber- culose-maladie en cas d'infection :

  • âge < 5 ans et surtout < 2 ans
  • Immunodépression (quelque soit la cause)
  • IRC avec hémodialyse

Ces facteurs sont cumulatifs.

Il est souvent proposé de considérer le risque d'infection comme significatif lorsque la durée de contact cumulée sur les 3 derniers mois est supérieure à 8 heures si le cas index est BAAR + et supérieure à 40 heures si le cas index est BAAR – et culture + .

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Each case detection system is a Bayesian network that represents the conditional probability distribution of findings and disease state (flu, NI-ILI, or other). This distribution can provide the probability of that patient’s findings given their assumed disease state. That is, P(E(p,d)|flu), P(E(p,d)|NI-ILI), and P(E(p,d)|other) where E(p,d) denotes the findings for patient p on day d.
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A Bayesian system to detect and characterize overlapping outbreaks
Bayesian network for Allegheny County contains 17 of the original 83 features, and the network for Salt Lake City contains 15. (The selected features are marked in Table 1 with “AC” or “SLC.”) <span>Each case detection system is a Bayesian network that represents the conditional probability distribution of findings and disease state (flu, NI-ILI, or other). This distribution can provide the probability of that patient’s findings given their assumed disease state. That is, P(E(p,d)|flu), P(E(p,d)|NI-ILI), and P(E(p,d)|other) where E(p,d) denotes the findings for patient p on day d. (Note that E(p,d) consists of 17 findings for each patient in Allegheny County and 15 findings for each patient in Salt Lake City due to feature selection.) These likelihoods—P(E(p,d)|f




we start with the full text of ED patient care reports. We use NLP to extract 79 features from each report, add four additional pre-coded features (including the result of a laboratory test), to represent each patient as a set of 83 features. We then use a case detection system to produce three likelihoods (P(E(p,d)|flu),P(E(p,d)|NI-ILI), and P(E(p,d)|other)) for each patient.
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A Bayesian system to detect and characterize overlapping outbreaks
h a patient’s findings are more or less likely given flu, NI-ILI, or other. This is in keeping with our Bayesian approach which seeks to build a model that best explains the data. To summarize, <span>we start with the full text of ED patient care reports. We use NLP to extract 79 features from each report, add four additional pre-coded features (including the result of a laboratory test), to represent each patient as a set of 83 features. We then use a case detection system to produce three likelihoods (P(E(p,d)|flu),P(E(p,d)|NI-ILI), and P(E(p,d)|other)) for each patient. Thus, the dataset given to MODS after preprocessing consists of three likelihoods for each patient. Additional details are provided in Appendix A. Although MODS does not categorically c




#155 #Cours #Facultaires #Médecine #Pédiatrie #Tuberculose
Les premières approches concluantes ont été la découverte de gènes de susceptibilité aux infections graves, sur la voie IL-12/interféron γ. La vaccination par le BCG diminue le risque d'évolution vers la tuberculose-maladie et, sur- tout, le risque d'évolution vers une forme disséminée. Il n'est pas certain que le BCG prévienne l'infection elle-même (voir chapitre 43)
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[unknown IMAGE 4822743780620] #155 #Cours #Facultaires #Médecine #Pédiatrie #Tuberculose #has-images

Étapes du dépistage (fig. 61.1) À la première évaluation, quel que soit l'âge de l'enfant :

Examen clinique complet

RxTho de face, facilement complétée par un profil si âge 5 ans (moins de 5 ans ?)

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MODS includes three kinds of influenza models corresponding to no outbreak, one chain of infections, and two chains of infections
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Aronis et al. 2017: A Bayesian system to detect and characterize overlapping outbreaks
ber of people in the Susceptible, Exposed and Infected, Infectious, and Recovered compartments each day using a set of difference equations [17]. 2.2.2. Modeling multiple outbreaks of influenza <span>MODS includes three kinds of influenza models corresponding to no outbreak, one chain of infections, and two chains of infections: • A Zero Outbreak Model is defined by b, a baseline level of infectious influenza cases in the general population. We denote the zero outbreak model with 〈b〉. • A Single Outbreak Model




[unknown IMAGE 4822742207756] #155 #Cours #Facultaires #Médecine #Pédiatrie #Tuberculose #has-images

Chez l'enfant immunocompétent âgé de moins de 5 ans, une IDR à la tuberculine (Tubertest ® ) est également systématiquement réalisée lors de cette première évaluation.

Les règles d'interprétation de l'IDR dépendent de la vaccination par le BCG (tableau 61.1).

Les tests interféron gamma (IFN-γ) ne sont actuellement pas recommandés pour le dépistage des enfants d'âge < 5 ans (HAS, 2011).

En l'absence de critères d'infection, une nouvelle évaluation par IDR et radiographie de thorax sera réalisée 8 à 12 semaines après le dernier contact avec le cas index.
Durant cet intervalle, les enfants âgés de moins de 2 ans doivent bénéficier d'une prophylaxie, c'est-à-dire en pratique d'un traitement d'infection tuberculeuse latente

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#155 #Cours #Facultaires #Médecine #Pédiatrie #Tuberculose
Chez l'enfant immunocompétent âgé de 5 ans ou plus, du fait du très faible risque de progression rapide vers la tuberculose-maladie, le test immunitaire n'est pas réalisé initialement si la radiographie de thorax est normale, mais seulement après un délai de 8 à 12 semaines après le dernier contact avec le cas index. Un test in vitro de libération d'IFN-γ (Quantiféron ® , SPOT-TB ® ) peut remplacer l'IDR. Tout test positif définit une infection tuberculeuse.
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#155 #Cours #Facultaires #Médecine #Pédiatrie #Tuberculose

Chez l'enfant immunodéprimé, le risque de progression rapide vers la tuberculose-maladie est élevé. La stratégie de dépistage est donc superposable à celle réalisée chez l'enfant âgé de moins de 5 ans.

Les tests immunitaires ont souvent une sensibilité diminuée dans ces situations, mais doivent néanmoins être réalisés.

Une prophylaxie est indiquée pour tous ces enfants, entre les deux évaluations.

Toute radiographie anormale doit faire considérer le diagnostic de tuberculose-maladie, quel que soit le résultat des tests immunitaires.

Quel que soit l'âge de l'enfant, toute infection tuberculeuse latente (ITL) à bacille supposé sensible doit être traitée

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#155 #Cours #Facultaires #Médecine #Pédiatrie #Tuberculose
Généralités Le diagnostic de tuberculose-maladie peut être difficile chez l'enfant, particulièrement chez le nourrisson. La tuberculose-maladie de l'enfant étant le plus souvent pauvre en bacilles, la preuve microbiologique fait souvent défaut, contrairement à la tuberculose de l'adulte. Le diagnostic est donc le plus souvent posé sur un faisceau d'arguments intégrant la notion de contage, la présence de signes cliniques, une réponse immunitaire spécifique positive (IDR ou test interféron gamma), et des anomalies radiologiques évocatrices
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[unknown IMAGE 4822747450636] #155 #Cours #Facultaires #Médecine #Pédiatrie #Tuberculose #has-images
Lorsque des symptômes sont présents, ils sont souvent peu spécifiques, mais attirent l'atten- tion par leur installation progressive et leur caractère traînant : t VOF JOGFDUJPO CSPODIPQVMNPOBJSF QFSTJTUBOUF SÏTJTUBOUF BVY BOUJCJPUJRVFT VTVFMT t VOF DBTTVSF QPOEÏSBMF JOFYQMJRVÏF EBOT VO DPOUFYUF Ë SJTRVF t VO ÏUBU TVCGÏCSJMF QSPMPOHÏ TVSUPVU TJ BTTPDJÏ Ë EFT TVFVST OPDUVSOFT t VOF BTUIÏOJF BWFD MÏUIBSHJF PV CBJTTF EhBDUJWJUÏ JOFYQMJRVÏFT t VO BTQFDU QTFVEP TFQUJRVF BWFD IÏQBUPTQMÏOPNÏHBMJF QBSGPJT PCTFSWÏ DIF[ MF OPVSSJTTPO âgé de moins de 3 mois
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#155 #Cours #Facultaires #Médecine #Pédiatrie #Tuberculose
L'examen microscopique est positif chez moins de 20 % des enfants avec une tuberculose- maladie. La culture est positive dans moins de 50 % des cas. Malgré cette faible rentabilité, les recherches microbiologiques sont systématiques devant toute suspicion de tuberculose-maladie. Leur positivité imposera un dépistage autour de l'enfant
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#155 #Cours #Facultaires #Médecine #Pédiatrie #Tuberculose

Imagerie thoracique

  • La radiographie de thorax peut être d'emblée très évocatrice, en montrant :
    • Des adénopathies latérotrachéales droites
    • Médiastinales et hilaires, typiques de la tuberculose de l'enfant (voir fig. 60.5 au chapitre 60).
      • Ces adénopathies peuvent comprimer les voies aériennes adjacentes avec éventuellement atélectasie ou emphysème obstructif.
    • Des opacités parenchymateuses alvéolaires sont également fréquentes.
    • Le classique complexe primaire, associant nodule parenchymateux d'un sommet et adénopathie satellite, est en fait rarement objectivé.
    • La présence de cavernes est rare chez l'enfant (sauf chez l'adolescent)

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#155 #Cours #Facultaires #Médecine #Pédiatrie #Tuberculose
Le scanner thoracique avec injection de produit de contraste permet de préciser les aspects radiologiques. Les adénopathies tuberculeuses ont typiquement un centre hypodense (nécrose) et une périphérie discrètement rehaussée lors de l'injection de produit de contraste (aspect toutefois inconstant chez l'enfant)
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#155 #Cours #Facultaires #Médecine #Pédiatrie #Tuberculose

Endoscopie bronchique

  • Elle est nécessaire pour objectiver l'atteinte endobronchique, et est réalisée dès que le scanner suggère une compression des voies aériennes.

  • Elle permet la mise en évidence de compressions extrinsèques par les adénopathies, les réactions inflammatoires de la paroi bronchique sous forme de granulome, et d'éventuelle fistulisation ganglionnaire avec irruption de caséum.

  • Les prélèvements endobronchiques, ou le lavage bronchoalvéolaire, n'ont pas de meilleur rendement microbiologique chez l'enfant que trois tubages gastriques consécutifs. L'endoscopie bronchique n'est donc pas réalisée à but uniquement microbiologique

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Flashcard 4822754528524

Question
To overcome SMC weight degeneracy, [...] can be inserted in order to rejuvenate the sequential sample
Answer
resampling steps

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To overcome SMC weight degeneracy, resampling steps can be inserted in order to rejuvenate the sequential sample

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Flashcard 4822756101388

Question
To overcome SMC weight degeneracy, resampling steps can be inserted in order to [...]
Answer
rejuvenate the sequential sample

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To overcome SMC weight degeneracy, resampling steps can be inserted in order to rejuvenate the sequential sample

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#155 #Cours #Facultaires #Médecine #Pédiatrie #Tuberculose
Traitements médicamenteux 1. Contage et infection tuberculeuse latente Une ITL de l'enfant doit être traitée par une bithérapie pendant 3 mois : t JTPOJB[JEF t SJGBNQJDJOF Chez les enfants âgés de moins de 2 ans ou les immunodéprimés exposés mais sans critère ini- tial d'infection, cette même bithérapie est proposée à titre prophylactique, jusqu'à la deuxième évaluation, 8 à 12 semaines après le dernier contact. Le traitement doit être administré en une prise unique le matin à jeun. La dose des antituberculeux est à adapter au poids de l'enfant, n'autorisant que rarement l'utilisation des formulations combinées (possible chez l'adolescent)
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[unknown IMAGE 4822765276428] #155 #Cours #Facultaires #Médecine #Pédiatrie #Tuberculose #has-images
Tuberculose-maladie Une tuberculose-maladie non compliquée de l'enfant doit être traitée par : t VOF USJUIÏSBQJF QFOEBOU øNPJTø JTPOJB[JEF SJGBNQJDJOF QZSB[JOBNJEF t TVJWJF EhVOF CJUIÏSBQJF QFOEBOU øNPJTø JTPOJB[JEF SJGBNQJDJOF La prescription d'éthambutol pendant les deux premiers mois n'est pas systématique chez l'enfant, et est réservée aux formes riches en bacilles, en cas de suspicion de BK résistant à l'INH, ou de tuberculose disséminée. L'utilisation d'une corticothérapie pendant les premières semaines est réservée aux diminu- tions du calibre bronchique de plus de 50 % et aux localisations méningées ou péricardiques.
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#155 #Cours #Facultaires #Médecine #Pédiatrie #Tuberculose
Les parents sont informés des éventuels signes de toxicité devant faire consulter en urgence : douleurs abdominales, vomissements, ictère. L'apparition de ces signes impose l'arrêt du trai- tement et la réalisation urgente d'un dosage de transaminases. L'ITL chez l'enfant < 15 ans est une maladie à déclaration obligatoire à l'ARS
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#155 #Cours #Facultaires #Médecine #Pédiatrie #Tuberculose
Tuberculose-maladie La fréquence du suivi clinique et radiologique doit être adaptée au tableau initial. Il peut être bimensuel initialement lorsque le risque de compression bronchique est important. Du fait de l'adjonction du pyrazinamide, la surveillance biologique des transaminases toutes les 2 semaines est impérative
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#155 #Cours #Facultaires #Médecine #Pédiatrie #Tuberculose
L'éviction de collectivité est obligatoire jusqu'à présentation d'un certificat médical de non- contagiosité.
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Flashcard 4822774189324

Tags
#MLBook #hyperparameter #machine-learning
Question
Discuss about a hyperparameter.
Answer
A hyperparameter is a property of a learning algorithm, usually (but not always) having a numerical value. That value influences the way the algorithm works. Hyperparameters aren’t learned by the algorithm itself from data. They have to be set by the data analyst before running the algorithm.

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A hyperparameter is a property of a learning algorithm, usually (but not always) having a numerical value. That value influences the way the algorithm works. Hyperparameters aren’t learned by the algorithm itself from data. They have to be set by the data analyst before running the algorithm. I show how to do that in Chapter 5.

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Flashcard 4822778907916

Tags
#MLBook #machine-learning #new-algorithms #reasons
Question

People invent new learning algorithms for one of the two main reasons:

  1. [...]
  2. The new algorithm has better theoretical guarantees on the quality of the model it produces.
Answer
The new algorithm solves a specific practical problem better than the existing algorithms.

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People invent new learning algorithms for one of the two main reasons: The new algorithm solves a specific practical problem better than the existing algorithms. The new algorithm has better theoretical guarantees on the quality of the model it produces.

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Flashcard 4822780480780

Tags
#MLBook #machine-learning #new-algorithms #reasons
Question

People invent new learning algorithms for one of the two main reasons:

  1. The new algorithm solves a specific practical problem better than the existing algorithms.
  2. [...]
Answer
The new algorithm has better theoretical guarantees on the quality of the model it produces.

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People invent new learning algorithms for one of the two main reasons: The new algorithm solves a specific practical problem better than the existing algorithms. The new algorithm has better theoretical guarantees on the quality of the model it produces.

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Flashcard 4822782840076

Tags
#algorithmic-advances #deep-learning #machine-learning
Question
Because the field is guided by experimental findings rather than by theory, algorithmic advances only become possible [...]. Machine learning isn’t mathematics or physics, where major advances can be done with a pen and a piece of paper. It’s an engineering science.
Answer
when appropriate data and hardware are available to try new ideas (or scale up old ideas, as is often the case)

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Because the field is guided by experimental findings rather than by theory, algorithmic advances only become possible when appropriate data and hardware are available to try new ideas (or scale up old ideas, as is often the case). Machine learning isn’t mathematics or physics, where major advances can be done with a pen and a piece of paper. It’s an engineering science.

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Flashcard 4822789655820

Tags
#FEM #RES.2-002 #linear-analysis
Question
My objective in this set of lectures is to introduce to you finite element methods for the linear analysis of solids and structures. ["Iinear" meaning [...]]
Answer
infinitesimally small displacements and linear elastic material properties (Hooke's law applies)

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My objective in this set of lectures is to introduce to you finite element methods for the linear analysis of solids and structures. ["Iinear" meaning infinitesimally small displacements and linear elastic material properties (Hooke's law applies)]

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Article 4822798306572

Chakraborty 2018: What to know before forecasting the flu
#has-images

journals.plos.org What to know before forecasting the flu Prithwish Chakraborty, 22-28 minutes Prithwish Chakraborty, Bryan Lewis, Stephen Eubank, John S. Brownstein, Madhav Marathe, Naren Ramakrishnan x Published: October 12, 2018 https://doi.org/10.1371/journal.pcbi.1005964 Citation: Chakraborty P, Lewis B, Eubank S, Brownstein JS, Marathe M, Ramakrishnan N (2018) What to know before forecasting the flu. PLoS Comput Biol 14(10): e1005964. https://doi.org/10.1371/journal.pcbi.1005964 Editor: Marcel Salathé, Ecole Polytechnique Federale de Lausanne, SWITZERLAND Published: October 12, 2018 Copyright: © 2018 Chakraborty et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Fundi



#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein

Anatomie

Le sein est constitué de glande mammaire (elle-même composée de 15 à 20 compartiments séparés par du tissu graisseux) et de tissu de soutien contenant des vaisseaux (sanguins et lymphatiques), des fibres et de la graisse ; les proportions de ces deux composants varient en fonction de facteurs individuels et de l'âge.

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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein
Le drainage lymphatique du sein se fait vers trois sites principaux : les nœuds lymphatiques du creux axillaire (les plus importants), les nœuds sus et sous-claviculaires, les nœuds de la chaîne mammaire interne.
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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein

Épidémiologie (données de l'INCa) :

  • Le cancer du sein est le cancer le plus fréquent chez la femme, devant le cancer colorectal et le cancer du poumon.
  • Son incidence augmente avec la généralisation du dépistage et le vieillissement de la population. En 2017, on estimait le nombre de nouveaux cas de cancers du sein en France métropolitaine à environ 59 000 et le nombre de décès à environ 11900.
  • Il représente plus du tiers de l'ensemble des nouveaux cas de cancer chez la femme.
  • Dans plus de 8 cas sur 10, il touche des femmes âgées de 50 ans et plus.
  • Dans plus de 99 % des cas, le cancer du sein touche les femmes mais il peut aussi concerner les hommes (chez qui une mutation constitutionnelle délétère doit être évoquée).
  • Son dépistage à un stade précoce permet un pronostic plus favorable avec un taux de survie nette standardisée sur l'âge à 5 ans de 87 % et à 10 ans de 76 %.
  • Le taux de mortalité a diminué de 1,5 % par an en moyenne entre 2005 et 2012.
  • Cependant, il reste la 1ère cause de décès par cancer chez la femme devant le cancer du poumon

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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein

Interrogatoire

Il recueille :

  • Les facteurs de risque de cancer du sein :
    • âge,
    • poids, taille, indice de masse corporelle (IMC) élevé ou s'élevant lors de la ménopause
    • antécédents gynéco-obstétricaux (facteurs d'exposition aux œstrogènes) :
      • ménarches précoces (< 12 ans)
      • ménopause tardive (> 55 ans)
      • âge tardif lors de la 1ère grossesse (> 30 ans)
      • allaitement artificiel
      • nulliparité
      • exposition aux traitements hormonaux (contraception œstroprogestative et traitement hormonal de la ménopause)
    • antécédents personnels de cancer du sein ou de mastopathie à risque (ex. : mastopathie fibrokystique avec présence d'atypies – hyperplasie atypique)
    • antécédents familiaux de cancer du sein, des ovaires, du côlon, de l'endomètre, avec connaissance éventuelle d'une prédisposition génétique (BRCA1, BRCA2, PALB2)

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Article 4822857288972

Funk et al. 2019: Assessing the performance of real-time epidemic forecasts: Ebola case study
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journals.plos.org Assessing the performance of real-time epidemic forecasts: A case study of Ebola in the Western Area region of Sierra Leone, 2014-15 Sebastian Funk , 57-72 minutes Open Access Peer-reviewed Research Article Sebastian Funk, Anton Camacho, Adam J. Kucharski, Rachel Lowe, Rosalind M. Eggo, W. John Edmunds x Published: February 11, 2019 https://doi.org/10.1371/journal.pcbi.1006785 Abstract Real-time forecasts based on mathematical models can inform critical decision-making during infectious disease outbreaks. Yet, epidemic forecasts are rarely evaluated during or after the event, and there is little guidance on the best metrics for assessment. Here, we propose an evaluation approach that disentangles different components of forecasting ability using metrics that separately assess the calibration, sharpness and bias of forecasts. This ma



#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein

Inspection

Elle recherche :

  • une augmentation du volume mammaire
  • l'existence ou non de signes cutanés : rougeur localisée ou étendue à l'ensemble du sein, œdème cutané (aspect de peau d'orange ; fig. 20.3), ulcération
  • un bombement (principalement dans le quadrant supéro-interne)
  • une rétraction (à rechercher grâce à un éclairage à jour frisant) de la peau (fig. 20.4) ou de la plaque aréolo-mamelonnaire (PAM) (fig. 20.5), examen réalisé les bras pendants puis relevés
  • aspect de maladie de Paget au niveau de la plaque aréolo-mamelonnaire (fig. 20.6)

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Article 4823080111372

Marr et al 2019: Effect of humidity on flu

royalsocietypublishing.org Mechanistic insights into the effect of humidity on airborne influenza virus survival, transmission and incidence 54-68 minutes Linsey C. Marr , Julian W. Tang , Jennifer Van Mullekom and Seema S. Lakdawala Published:16 January 2019https://doi.org/10.1098/rsif.2018.0298 Abstract Influenza incidence and seasonality, along with virus survival and transmission, appear to depend at least partly on humidity, and recent studies have suggested that absolute humidity (AH) is more important than relative humidity (RH) in modulating observed patterns. In this perspective article, we re-evaluate studies of influenza virus survival in aerosols, transmission in animal models and influenza incidence to show that the combination of temperature and RH is equally valid as AH as a predictor. Collinearity must be considered, as higher levels of AH are only possible at higher temperatures, where it i



#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein

Palpation

  • Elle est effectuée mains à plat, par une pression douce par mouvements rotatifs faisant rouler la glande sur le grill costal, quadrant par quadrant, en insistant sur le quadrant supéroexterne (environ 60 % des cancers se localisent dans ce quadrant ou à la jonction des quadrants adjacents) et évalue :
    • La localisation (quadrant)
    • La taille (en mm)
    • La consistance et la sensibilité
    • La netteté des contours
    • La mobilité par rapport à la peau (par le pincement de la peau en regard de la tumeur, à la recherche d'une adhérence voire d'un envahissement) et aux plans profonds par la manœuvre de Tillaux (adduction contrariée du bras, permettant la contraction du muscle grand pectoral), uniquement pour les tumeurs situées en regard du muscle grand pectoral

  • La pression mamelonnaire à la recherche d'un écoulement, qui peut être considéré comme :
    • Suspect s'il est d'apparition récente, spontané, unilatéral, unicanalaire, de couleur claire (translucide), jaune (séreux), rouge (sanglant) ou noir.
    • Non suspect s'il est ancien et intermittent, provoqué, bilatéral, pluricanalaire, de couleur blanche (aspect lactescent, crémeux), marron ou verdâtre

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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein

Examen des aires lymphonodales

Il étudie :

  • Les aires axillaires et sus-claviculaires (examen bilatéral et comparatif) ; les aires mammaires internes ne sont pas accessibles à l'examen clinique
  • Les signes d'envahissement : appréciés sur le volume, la consistance et la mobilité des adénopathies

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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein

Mammographie :

  • C'est l'examen réalisé en 1ère intention, sauf chez les femmes très jeunes (âge < 30 ans)
  • Elle doit être réalisée de préférence en 1ère partie du cycle
  • Elle peut être réalisée dans le cadre du dépistage (mammographie de dépistage comportant 2 incidences systématiques : craniocaudale [face] et médiolatérale oblique [oblique externe]) ou en présence de symptômes (mammographie de diagnostic comportant au minimum 3 incidences : face, profil strict et profil axillaire)

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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein

La mammographie de dépistage a pour objectif de mettre en évidence des cancers de petite taille, à un stade précoce, avant l'apparition de symptômes.

Cet examen peut être réalisé :

  • Soit dans le cadre du programme national de dépistage organisé du cancer du sein destiné aux femmes âgées de 50 à 74 ans, tous les 2 ans.
    • Une 2 e lecture est systématiquement réalisée pour tous les bilans mammographiques jugés normaux en 1ère lecture.
    • En cas de discordance entre ces deux lectures, une 3ème lecture est organisée avec un radiologue expert

  • Soit à titre individuel, notamment lorsqu'une femme présente des facteurs de risque particuliers (antécédents personnels et/ou familiaux notamment)

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Article 4823085616396

Nsoesie et al. 2014: Systematic review of flu outbreak forecasts

onlinelibrary.wiley.com A systematic review of studies on forecasting the dynamics of influenza outbreaks Elaine O. Nsoesie 35-44 minutes Abstract Forecasting the dynamics of influenza outbreaks could be useful for decision‐making regarding the allocation of public health resources. Reliable forecasts could also aid in the selection and implementation of interventions to reduce morbidity and mortality due to influenza illness. This paper reviews methods for influenza forecasting proposed during previous influenza outbreaks and those evaluated in hindsight. We discuss the various approaches, in addition to the variability in measures of accuracy and precision of predicted measures. PubMed and Google Scholar searches for articles on influenza forecasting retrieved sixteen studies that matched the study criteria. We focused on studies that aimed at forecasting influenza outbreaks at the local, regional, national, or global level. The selected studies s



#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein

Devant la présence d'anomalies, des incidences complémentaires seront réalisées :

  • Médio-latérale (profil), clichés localisés, localisés agrandis, etc.
  • Dans ces situations, le recours à la tomosynthèse est très utile.
  • Les critères de qualité sont importants, surtout pour l'incidence oblique : visualisation du sillon sous-mammaire et du muscle grand pectoral

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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein
La mammographie permet de guider les biopsies ou le repérage de lésions non palpables : en cas d'images ACR 4 ou ACR 5 (cf. fig. 20.7 et 20.8), des prélèvements par biopsie percutanée sont nécessaires
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Article 4823216426252

Schon et al. 2018: SMC for nonlinear dynamic systems
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sciencedirect.com Probabilistic learning of nonlinear dynamical systems using sequential Monte Carlo Abstract Probabilistic modeling provides the capability to represent and manipulate uncertainty in data, models, predictions and decisions. We are concerned with the problem of learning probabilistic models of dynamical systems from measured data. Specifically, we consider learning of probabilistic nonlinear state-space models. There is no closed-form solution available for this problem, implying that we are forced to use approximations. In this tutorial we will provide a self-contained introduction to one of the state-of-the-art methods—the particle Metropolis-Hastings algorithm—which has proven to offer a practical approximation. This is a Monte Carlo based method, where the particle filter is used to guide a Markov chain Monte Carlo method through the parameter space. One of the key merits of the particle Metropolis-Hastings algorithm is that it is guaranteed to converge to the “



#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein

Échographie

Échographie du sein :

  • Elle peut être réalisée à n'importe quel moment du cycle.

  • Elle est effectuée en complément de la mammographie, mais parfois il s'agit du seul examen (femmes très jeunes d'âge < 30 ans)
  • Elle présente un grand intérêt pour les femmes ayant des seins denses +++ et chez la femme enceinte (évite les risques d'irradiation)

  • Elle est plus performante que la mammographie pour déterminer la taille de la tumeur et analyser sa structure interne

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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein

Échographie axillaire

  • Elle est réalisée en cas d'adénopathie cliniquement suspecte (recommandation INCa 2012).

  • Cette exploration fait aujourd'hui partie du bilan systématique préopératoire d'un cancer du sein.
    Elle permet d'effectuer des prélèvements échoguidés cytologiques et anatomopathologiques.

  • Cet examen a donc un intérêt thérapeutique en cas de positivité de la ponction lymphonodale.
    Il permet d'éviter la pratique du nœud lymphatique sentinelle pour proposer un curage axillaire d'emblée.

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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein

IRM mammaire (fig. 20.10) :

  • Il s'agit d'un examen de 2 ème intention, très sensible (> 90 %) mais peu spécifique (70 à 85 %), en particulier chez la femme jeune.

  • L'IRM est réalisée de préférence en 1ère partie du cycle, uniquement dans certaines indications :
    • Bilan complémentaire lorsque l'imagerie standard (mammographie ou échographie) ne permet pas de conclure avec certitude à l'absence de malignité
    • Adénopathie métastatique d'un cancer du sein et bilan sénologique normal
    • Bilan d'extension dans le cadre d'un carcinome lobulaire invasif (volontiers multifocal et bilatéral)
    • Recherche d'une récidive locale après traitement conservateur (aide au diagnostic avec un foyer de cytostéatonécrose)
    • Surveillance des patientes sous chimiothérapie néoadjuvante
    • Patiente mutée BRCA1, BRCA2 ou à haut risque génétique familial (couplée à la mammographie et à l'échographie dans le cadre de la surveillance annuelle)
    • Suspicion (clinique et/ou échographique) de rupture prothétique en cas de reconstruction mammaire par prothèse

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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein

Prélèvements biopsiques percutanés :

À type de microbiopsies (masse palpable) ou macrobiopsies (foyers de microcalcifications), elles sont réalisées quasi systématiquement en préopératoire, réduisant ainsi la place de l'examen extemporané peropératoire et permettant de définir avec la patiente une conduite à tenir avant l'intervention

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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein
Le guidage des microbiopsies se fait le plus souvent sous échographie (masse échographique) et celui des macrobiopsies le plus souvent sous stéréotaxie (foyer de microcalcifications mammographique)
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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein
En revanche, la cytologie d'un écoulement mamelonnaire peut être utile en cas d'écoulement suspect (sanglant +++).
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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein

Prise en charge d'un cancer du sein

  • Le cancer du sein est un cancer le plus souvent hormonodépendant.
  • Deux types de cancers infiltrants sont distingués selon le siège initial des lésions :
    • Canalaire (ou carcinome non spécifique) : 90 % des cancers

    • Lobulaire : 10 % des cancers particuliers dans leur forme commune par leur bon histopronostic et par le manque de cohésion des cellules qui infiltrent les tissus « en file indienne » (du fait de la perte de la e-cadhérine qui permet aux cellules de s'agréger les unes aux autres).

    • Il existe de même deux types de cancer du sein non infiltrants, beaucoup moins fréquents : les carcinomes canalaires in situ ou intracanalaires (fig. 20.12), et les très rares carcinomes lobulaires in situ (LIN 3)

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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein
L'apparition d'un nodule du sein chez une femme ménopausée témoigne d'un cancer du sein jusqu'à preuve du contraire.
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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein
La taille tumorale reste un des principaux facteurs pronostiques.
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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein
Enfin, n'oublions pas que les cancers du sein et de l'endomètre surviennent volontiers sur les mêmes terrains et que les mutations BRCA sont responsables aussi de lésions ovariennes ou péritonéales, c'est dire que l'examen gynécologique doit être réalisé systématiquement chez ces patientes
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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein

Bilan sénologique (mammographie/échographie) :

  • Image suspecte classée ACR 4 ou 5 :
    • À la mammographie, il s'agit d'une masse dense spiculée (fig. 20.13), d'une rupture architecturale (fig. 20.14), de microcalcifications regroupées, plus ou moins branchées, et semblant suivre un galactophore.

    • À l'échographie mammaire, on retrouve un nodule hypoéchogène, irrégulier, de grand axe perpendiculaire à la peau pouvant être associé à un cône d'ombre postérieur.

    • L'échographie du creux axillaire, en cas d'adénopathies axillaires suspectes cliniquement, retrouve des nœuds lymphatiques axillaires augmentés de taille

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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein

Donner des facteurs pronostiques (uniquement pour les carcinomes infiltrants) :

  • Grade histologique de Scarff Bloom Richardson reposant sur :
    • la différenciation tumorale
    • les atypies cellulaires
    • le compte des mitoses

  • Emboles vasculaires (présence/absence)
  • Marqueurs de prolifération : Ki 67, cytométrie de flux (phase S) ; la place du Ki 67 est controversée
  • Récepteurs hormonaux (RH) à l'œstrogène et à la progestérone (positifs/négatifs)
    • HER2 (0, +, ++, +++) : seul HER2 +++ est considéré comme positif

  • Envahissement lymphonodal

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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein

Au total :

Les facteurs de mauvais pronostic faisant poser l'indication d'une chimiothérapie sont :

  • L'âge < 35 ans, la taille de la lésion ≥ pT2 cm
  • L'envahissement lymphonodal (discussion au cas par cas)
  • Les récepteurs hormonaux négatifs
  • La sur expression HER2 (à 3 +)
  • La présence d'emboles vasculaires.

Les facteurs prédictifs de réponse au traitement sont :

  • Les RH qui prédisent l'efficacité de l'hormonothérapie en cas de positivité
  • La surexpression HER2 à 3 + qui prédit l'efficacité du trastuzumab (Herceptin®)

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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein

Pour information

En regroupant plusieurs de ces facteurs, on distingue actuellement 4 grands groupes de tumeurs (classification moléculaire) :

  • Tumeurs luminales A (RE et/ou RP positifs, HER2 négatif)
  • Tumeurs luminales B (RE ou RP positif, HER2 positif)
  • Tumeurs triples négatives (RE, RP et HER2 négatifs)
  • Tumeurs HER2 positives (RE et RP négatifs, HER2 positif)

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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein

En parallèle de la prise en charge médicale, les patientes bénéficient d'un accompagnement par une infirmière (infirmière d'annonce) et un(e) psychologue.

L'ensemble des soins, examens, transports, etc. est pris en charge à 100 % par la sécurité Sociale

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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein

Prise en charge des carcinomes intracanalaires (fig. 20.15)

Bilan préopératoire :

  • Il est nécessaire d'effectuer un repérage radiologique préopératoire (lésions le plus souvent infracliniques)
  • On ne réalise pas de bilan d'extension car il n'existe pas de risque métastatique
  • Il n'y a pas d'indication à réaliser une IRM mammaire.

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#309 #Cancer #Cours #Facultaires #Gynécologie #Médecine #Sein

Traitement : (Carcinomes INTRA-canalaires)

  • La prise en charge chirurgicale est conservatrice (zonectomie ou tumorectomie) ou radicale (mammectomie) en fonction de :
    • la taille lésionnelle
    • du nombre de foyers
    • du volume des seins
  • La marge de tissus sains tout autour du carcinome doit être ≥ 2 mm.
  • En cas de tumorectomie, une radiothérapie systématique est entreprise au niveau du sein après l'intervention
  • En cas de mammectomie, on n'effectue pas de radiothérapie ; une reconstruction mammaire immédiate est possible.
  • Il n'y a pas d'indication pour le nœud lymphatique sentinelle : il peut se discuter au cas par cas en cas de carcinome intracanalaire ou lobulaire de haut grade avec territoire lésionnel étendu (indication de mammectomie), lorsqu'il existe un doute de micro-invasion, ou encore lorsque la lésion est palpable

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Prise en charge des carcinomes infiltrants (fig. 20.16 et 20.17) :

Bilan d'extension :

  • La taille de la tumeur et l'envahissement lymphonodal sont les deux principaux facteurs prédictifs de métastases asymptomatiques.
  • Les sites métastatiques préférentiels sont les os, les poumons et le foie

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On effectue un bilan d'extension préopératoire seulement en présence de facteurs pronos-tiques péjoratifs :

  • Cliniques :
    • Tumeurs T3, T4
    • Envahissement lymphonodal (N+)
    • Signe(s) d'appel
  • Anatomopathologiques/biologiques :
    • Grade 3
    • Récepteurs hormonaux négatifs (RH–)
    • HER2 positif (HER2 +++)

Les indications en option à discuter en RCP sont les suivantes :

  • Tumeurs T2
  • Présence d'emboles vasculaires
  • pN1 micrométastatique
  • Ki 67 (> 20 %)

Dans ce cas, le bilan de 1ère intention peut reposer sur l'une des deux options suivantes :

  • TDM thoraco-abdomino-pelvienne et scintigraphie osseuse
  • TEP-TDM au 18 FDG
  • (RP + Echo-abdo + Scinti os dans le CNEC)

  • Le dosage du CA15-3 ne figure plus dans aucun référentiel, ni pour le diagnostic ni en bilan d'extension métastatique

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À titre d'information

La réalisation d'une IRM cérébrale systématique, dans le cadre du bilan initial chez des patientes asymptomatiques atteintes de tumeurs surexprimant HER2 n'est pas justifiée

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la réalisation d'une reconstruction mammaire immédiate en cas de radiothérapie ou chimiothérapie prévue(s) ou possible(s) en postopératoire est à discuter en RCP
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Le traitement est conservateur (tumorectomie, ou zonectomie si tumeur non palpable) ou radical (mammectomie) en fonction de : (Carcinome canalaire sinfiltrants)

  • La taille tumorale
  • Du nombre de foyers
  • Du volume du sein
  • Des lésions associées éventuelles (carcinome in situ +++)

  • Le traitement chirurgical conservateur du sein dépend de la taille de l'exérèse nécessaire pour obtenir l'exérèse complète de la tumeur en marges saines et du volume du sein pour un résultat cosmétique satisfaisant.
    Il s'associe systématiquement à une radiothérapie de la glande mammaire.

  • En cas de contre-indication à la radiothérapie du sein, il ne peut y avoir de traitement conservateur

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Au niveau de l'aire axillaire :

Le nœud sentinelle (NS) est le premier nœud de drainage de la glande mammaire : son analyse anatomopathologique, lorsqu'elle est négative, permet de s'affranchir du curage lymphonodal plus morbide.
Il implique un double repérage par injection de gadolinium et de bleu de patente et, de façon plus récente, par fluorescence en utilisant de l'indocyanine green

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Si la taille tumorale est > 3 cm, et jusqu'à 5 cm selon certaines recommandations, ou en cas de nœud envahi en préopératoire (ponction positive sous échographie) : un curage axillaire est réalisé d'emblée
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es complications postopératoires du curage axillaire peuvent être : – immédiates : hématome, lymphocèle, troubles neurologiques sensitifs du creux axil- laire et de la face interne du bras, – à distance : algoneurodystrophie, enraidissement de l'épaule, lymphœdème du membre supérieur
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Le traitement chirurgical est indiqué lorsque le rapport volume tumoral/volume du sein ne permet pas un traitement conservateur d'emblée (cf. fig. 20.17) et en cas de tumeur mammaire unique non inflammatoire.
Il existe alors deux options thérapeutiques :

  • Soit mammectomie + curage axillaire

  • Soit chimiothérapie néoadjuvante :
    • Le traitement comporte en général 6 cycles avec un suivi de la réponse tumorale par l'examen clinique et l'imagerie (IRM +++) (cf. fig. 20.10) :
      • Réponse tumorale insuffisante : mammectomie + curage axillaire
      • Réponse tumorale permettant un traitement conservateur (en cas de réponse complète [RC], avec disparition de la tumeur, ou de réponse partielle mais avec un rapport volume tumoral/volume du sein devenu favorable pour la conservation du sein) : tumorectomie ou zonectomie + curage axillaire.

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Radiothérapie :

  • On effectue une radiothérapie du sein restant (systématique) ou de la paroi thoracique (en cas de mammectomie et tumeur localement évoluée) et des aires lymphonodales (en cas d'envahissement lymphonodal) mammaires internes et sus-claviculaires (qui peuvent être irradiées de principe en cas de nœud axillaire positif ou de tumeur à localisation centrale ou interne ou de volumineuse tumeur).

  • La radiothérapie du creux axillaire n'est pas envisagée en cas de curage axillaire réalisé, en raison du risque de lymphœdème et de l'absence de bénéfice sur le contrôle local et la survie

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Traitements médicaux Ils sont discutés en RCP post-thérapeutique après réception des résultats des examens prati- qués sur les prélèvements opératoires
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Chimiothérapie

Elle peut être de 2 types :

  • Adjuvante selon les données pronostiques :
    • Taille tumorale ≥ 2 cm
    • Atteinte lymphonodale axillaire
    • Agressivité histologique (grade 3, récepteurs hormonaux négatifs, HER2+)
    • Âge de la patiente (femmes jeunes +++ < 35 ans)
    • En cas de tumeur particulière (triple négative, ou HER2+)

  • Néoadjuvante en cas de tumeur évoluée non accessible à un traitement conservateur d'emblée, inflammatoire, ou de tumeur particulière (triple négative, ou HER2+)

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Il s'agit d'une polychimiothérapie comportant une anthracycline (FEC 100 : 5-FU, épirubicine, cyclophosphamide) et du paclitaxel (Taxol ® ).

La toxicité est veineuse (intérêt de la pose d'une chambre implantable), hématologique (leucémies secondaires), cutanée (éruptions, pigmentation, alopécie), digestive (nausées vomissements, diarrhée), hormonale (ménopause iatrogène), neurologique (avec les taxanes), cardiaque (avec les anthracyclines)

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Thérapie ciblée :

  • Le trastuzumab (Herceptin ® ) est un anticorps monoclonal inhibant la prolifération des cellules surexprimant HER2 (à 3 +).
  • Il est délivré en association avec la chimiothérapie et pendant 1 an (18 perfusions au total), en concomitance du paclitaxel (Taxol ® ) et de la radiothérapie.
  • Il a pour effet secondaire d'être cardiotoxique

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Hormonothérapie :

  • En cas de récepteurs hormonaux positifs, elle est prescrite pour une durée de 5 ans, parfois étendue jusqu'à 10 ans lorsqu'il existe une atteinte lymphonodale

  • Elle est à valider en RCP sous forme :
    • Adjuvante :
      • Avant la ménopause, par antiœstrogène (TAMOXIFENE, existe sous forme génériquée), 1 cp à 20 mg/j. Sa toxicité entraine :
        • Prise de poids
        • Maladie thromboembolique (l'antécédent de maladie thromboembolique est une contre-indication à sa prescription)
        • Augmentation du risque de cancer de l'endomètre

      • Chez les patientes < 35 ans avec facteurs de gravité, une suppression ovarienne (analogues de la LH-RH) est discutée en RCP

      • Après la ménopause, par antiaromatase (ANASTROZOLE [Arimidex ® ], LETROZOLE [Fémara ® ], EXEMESTANE [Aromasine ® ], existent aussi sous forme génériquée), 1 cp/j. Leur toxicité entraîne :
        • Bouffées vasomotrices
        • Troubles de l'humeur
        • Prise de poids
        • Arthromyalgies
        • Dyslipidémie
        • Ostéoporose

      • En cas de contre-indication aux antiaromatases en post-ménopause, le traitement peut être fait par du TAMOXIFENE

    • Parfois néoadjuvante chez les patientes ménopausées RH+ avant chirurgie : tumorectomie/ curage axillaire ou mammectomie/curage axillaire selon la réponse tumorale.
      ​​​​​​​Cette option peu fréquente est à valider en RCP

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Suivi cancer du sein.

  • Un examen clinique biannuel les 5 premières années, puis annuel.
  • Mammographie ± écho- graphie sont pratiquées chaque année à vie.
  • Les autres examens sont réalisés à la demande.
  • Aucun autre examen systématique n'est pratiqué chez une patiente asymptomatique, notamment pas de recherche systématique de métastase

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Elle peut être utile à chaque fois qu'existe un contexte héréditaire.

Le but de la consultation est la recherche d'une mutation portant actuellement principalement sur les gènes BRCA1, BRCA2 ou PALB2, devant des antécédents personnels et/ou familiaux évocateurs :

  • Antécédents personnels :
    • Femme < 36 ans
    • Cancer du sein de type médullaire
    • Cancer du sein triple négatif avant l'âge de 51 ans.
    • Cancer du sein chez un homme
    • Cancer du sein et de l'ovaire chez la même patiente
    • Cancer de l'ovaire survenant avant l'âge de 71 ans
    • Cancer du sein bilatéral (synchrone ou non)

  • Antécédents familiaux :
    • Au moins 3 cancers du sein chez des personnes apparentées du 1er et 2ème degré
    • Au moins 2 cancers du sein chez des personnes apparentées du 1er et 2ème degré âgées de moins de 70 ans, dont une de moins de 50 ans.

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When a female child is born, each ovum is surrounded by a single layer of granulosa cells; the ovum, with this granulosa cell sheath, is called a primordial follicle, as shown in the figure.

Throughout childhood, the granulosa cells are believed to provide nourishment for the ovum and to secrete an oocyte maturation inhibiting factor that keeps the ovum suspended in its primordial state in the prophase stage of meiotic division.

Then, after puberty, when FSH and LH from the anterior pituitary gland begin to be secreted in significant quantities, the ovaries (together with some of the follicles within them) begin to grow.

The first stage of follicular growth is moderate enlargement of the ovum, which increases in diameter twofold to threefold. That stage is followed by growth of additional layers of granulosa cells in some of the follicles. These follicles are known as primary follicles

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Development of Antral and Vesicular Follicles.

During the first few days of each monthly female sexual cycle, the concentrations of both FSH and LH secreted by the anterior pituitary gland increase slightly to moderately, with the increase in FSH slightly greater than that of LH and preceding it by a few days.

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The theca is divided into two layers.

  • In the theca interna, the cells take on epithelioid characteristics similar to those of the granulosa cells and develop the ability to secrete additional steroid sex hormones (estrogen and progesterone).
  • The outer layer, the theca externa, develops into a highly vascular connective tissue capsule that becomes the capsule of the developing follicle.

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After the early proliferative phase of growth, which lasts for a few days, the mass of granulosa cells secretes a follicular fluid that contains a high concentration of estrogen, one of the important female sex hormones (discussed later).

Accumulation of this fluid causes an antrum to appear within the mass of granulosa cells

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In addition, spindle cells derived from the ovary interstitium collect in several layers outside the granulosa cells, giving rise to a second mass of cells called the theca
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The early growth of the primary follicle up to the antral stage is stimulated mainly by FSH alone.

Greatly accelerated growth then occurs, leading to still larger follicles called vesicular follicles.

This accelerated growth is caused by the following mechanisms:
1. Estrogen is secreted into the follicle and causes the granulosa cells to form increasing numbers of FSH receptors, which causes a positive feedback effect because it makes the granulosa cells even more sensitive to FSH.
2. The pituitary FSH and the estrogens combine to promote LH receptors on the original granulosa cells, thus allowing LH stimulation to occur in addition to FSH stimulation and creating an even more rapid increase in follicular secretion.

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3. The increasing estrogens from the follicle plus the increasing LH from the anterior pituitary gland act together to cause proliferation of the follicular thecal cells and increase their secretion as well.

Once the antral follicles begin to grow, their growth occurs almost explosively.

The ovum also enlarges in diameter another threefold to fourfold, giving a total ovum diameter increase up to 10-fold, or a mass increase of 1000-fold.

As the follicle enlarges, the ovum remains embedded in a mass of granulosa cells located at one pole of the follicle

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Only One Follicle Fully Matures Each Month, and the Remainder Undergo Atresia.

After a week or more of growth—but before ovulation occurs—one of the follicles begins to outgrow all the others, and the remaining 5 to 11 developing follicles involute (a process called atresia); these follicles are said to become atretic.

The cause of the atresia is unclear, but it has been postulated to be the following:

  • The large amounts of estrogen from the most rapidly growing follicle act on the hypothalamus to depress further enhancement of FSH secretion by the anterior pituitary gland, in this way blocking further growth of the less well-developed follicles.
  • Therefore, the largest follicle continues to grow because of its intrinsic positive feedback effects, while all the other follicles stop growing and actually involute

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The single follicle reaches a diameter of 1 to 1.5 centimeters at the time of ovulation and is called the mature follicle
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Ovulation

  • Ovulation in a woman who has a normal 28-day female sexual cycle occurs 14 days after the onset of menstruation.

  • Shortly before ovulation the protruding outer wall of the follicle swells rapidly, and a small area in the center of the follicular capsule, called the stigma, protrudes like a nipple.
  • In another 30 minutes or so, fluid begins to ooze from the follicle through the stigma, and about 2 minutes later, the stigma ruptures widely, allowing a more viscous fluid, which has occupied the central portion of the follicle, to evaginate outward.
  • This viscous fluid carries with it the ovum surrounded by a mass of several thousand small granulosa cells, called the corona radiata

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A Surge of Luteinizing Hormone Is Necessary for Ovulation.

  • LH is necessary for final follicular growth and ovulation.
    Without this hormone, even when large quantities of FSH are available, the follicle will not progress to the stage of ovulation.

  • About 2 days before ovulation, the rate of secretion of LH by the anterior pituitary gland increases markedly, rising 6- to 10-fold and peaking about 16 hours before ovulation

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FSH also increases about twofold to threefold at the same time, and the FSH and LH act synergistically to cause rapid swelling of the follicle during the last few days before ovulation.

The LH also has a specific effect on the granulosa and theca cells, converting them mainly to progesterone-secreting cells.
Therefore, the rate of secretion of estrogen begins to fall about 1 day before ovulation, while increas-ing amounts of progesterone begin to be secreted

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It is in this environment of :

  • (1) rapid growth of the follicle
  • (2) diminishing estrogen secretion after a prolonged phase of excessive estrogen secretion
  • (3) initiation of secretion of progesterone

that ovulation occurs.

Without the initial preovulatory surge of LH, ovulation will not take place

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This LH causes rapid secretion of follicular steroid hormones that contain progesterone.

Within a few hours, two events occur, both of which are necessary for ovulation:

  • 1. The theca externa (i.e., the capsule of the follicle) begins to release proteolytic enzymes from lysosomes, and these enzymes cause dissolution of the follicular capsular wall and consequent weakening of the wall, resulting in further swelling of the entire follicle and degeneration of the stigma.
  • 2. Simultaneously there is rapid growth of new blood vessels into the follicle wall, and at the same time, prostaglandins (local hormones that cause vasodilation) are secreted into the follicular tissues

These two effects cause plasma transudation into the follicle, which contributes to follicle swelling

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These two effects cause plasma transudation into the follicle, which contributes to follicle swelling.
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combination of follicle swelling and simultaneous degen- eration of the stigma causes follicle rupture, with dis- charge of the ovum.
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CORPUS LUTEUM—THE LUTEAL PHASE OF THE OVARIAN CYCLE During the first few hours after expulsion of the ovum from the follicle, the remaining granulosa and theca interna cells change rapidly into lutein cells. They enlarge in diameter two or more times and become filled with lipid inclusions that give them a yellowish appearance. This process is called luteinization, and the total mass of cells together is called the corpus luteum, which is shown in Figure 82-5. A well-developed vascular supply also grows into the corpus luteum
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The granulosa cells in the corpus luteum develop extensive intracellular smooth endoplasmic reticula that form large amounts of the female sex hormones proges- terone and estrogen (with more progesterone than estro- gen during the luteal phase). The theca cells form mainly the androgens androstenedione and testosterone rather than female sex hormones. However, most of these hor- mones are also converted by the enzyme aromatase in the granulosa cells into estrogens, the female hormones
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The corpus luteum normally grows to about 1.5 centi- meters in diameter, reaching this stage of development 7 to 8 days after ovulation. Then the corpus luteum begins to involute and eventually loses its secretory function and its yellowish, lipid characteristic about 12 days after ovu- lation, becoming the corpus albicans; during the ensuing few weeks, the corpus albicans is replaced by connective tissue and over months is absorbed
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Luteinizing Function of Luteinizing Hormone. The change of granulosa and theca interna cells into lutein cells is dependent mainly on LH secreted by the anterior pituitary gland. In fact, this function gives LH its name— “luteinizing,” for “yellowing.” Luteinization also depends on extrusion of the ovum from the follicle. A yet unchar- acterized local hormone in the follicular fluid, called luteinization-inhibiting factor, seems to hold the lutein- ization process in check until after ovulation
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Secretion by the Corpus Luteum: An Additional Function of Luteinizing Hormone. The corpus luteum is a highly secretory organ, secreting large amounts of both progesterone and estrogen. Once LH (mainly that secreted during the ovulatory surge) has acted on the granulosa and theca cells to cause luteinization, the newly formed lutein cells seem to be programmed to go through a preordained sequence of (1) proliferation, (2) enlarge- ment, and (3) secretion, followed by (4) degeneration. All this occurs in about 12 days
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Involution of the Corpus Luteum and Onset of the Next Ovarian Cycle. Estrogen in particular and proges- terone to a lesser extent, secreted by the corpus luteum during the luteal phase of the ovarian cycle, have strong feedback effects on the anterior pituitary gland to main- tain low secretory rates of both FSH and LH. In addition, the lutein cells secrete small amounts of the hormone inhibin, the same as the inhibin secreted by the Sertoli cells of the male testes. This hormone inhibits FSH secretion by the anterior pituitary gland. Low blood concentrations of both FSH and LH result, and loss of these hormones finally causes the corpus luteum to degenerate completely, a process called involution of the corpus luteum.
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Final involution normally occurs at the end of almost exactly 12 days of corpus luteum life, which is around the 26th day of the normal female sexual cycle, 2 days before menstruation begins. At this time, the sudden cessation of secretion of estrogen, progesterone, and inhibin by the corpus luteum removes the feedback inhibition of the anterior pituitary gland, allowing it to begin secreting increasing amounts of FSH and LH again. FSH and LH initiate the growth of new follicles, beginning a new ovarian cycle. The paucity of secretion of progesterone and estrogen at this time also leads to menstruation by the uterus, which will be explained later
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The two types of ovarian sex hormones are the estrogens and the progestins. By far the most important of the estro- gens is the hormone estradiol, and by far the most impor- tant progestin is progesterone.
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The estrogens mainly promote proliferation and growth of specific cells in the body that are responsible for the development of most secondary sexual characteristics of the female. The pro- gestins function mainly to prepare the uterus for preg- nancy and the breasts for lactation
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CHEMISTRY OF THE SEX HORMONES Estrogens. In the normal nonpregnant female, estrogens are secreted in significant quantities only by the ovaries, although minute amounts are also secreted by the adre- nal cortices. During pregnancy, large quantities of estro- gens are also secreted by the placenta, as discussed in Chapter 83
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Only three estrogens are present in significant quanti- ties in the plasma of the human female: β-estradiol, estrone, and estriol,
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The principal estrogen secreted by the ovaries is β-estradiol. Small amounts of estrone are also secreted, but most of this is formed in the peripheral tissues from androgens secreted by the adrenal cortices and by ovarian thecal cells. Estriol is a weak estrogen; it is an oxidative product derived from both estradiol and estrone, with the conversion occurring mainly in the liver
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The estrogenic potency of β-estradiol is 12 times that of estrone and 80 times that of estriol
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β-estradiol is considered the major estrogen, although the estrogenic effects of estrone are not negligible
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Progestins. By far the most important of the progestins is progesterone. However, small amounts of another progestin, 17-α-hydroxyprogesterone, are secreted along with progesterone and have essentially the same effects. Yet, for practical purposes, it is usually reasonable to consider progesterone to be the only important progestin
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In the nonpregnant female, progesterone is usually secreted in significant amounts only during the latter half of each ovarian cycle, when it is secreted by the corpus luteum. As we shall see in Chapter 83, large amounts of pro- gesterone are also secreted by the placenta during preg- nancy, especially after the fourth month of gestation.
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synthesized in the ovaries mainly from cholesterol derived from the blood but also to a slight extent from acetyl coenzyme A, multiple molecules of which can combine to form the appropriate steroid nucleus
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During synthesis, mainly progesterone and androgens (testosterone and androstenedione) are synthesized first; then, during the follicular phase of the ovarian cycle, before these two initial hormones can leave the ovaries, almost all the androgens and much of the progesterone are converted into estrogens by the enzyme aromatase in the granulosa cells. Because the theca cells lack aro- matase, they cannot convert androgens to estrogens. However, androgens diffuse out of the theca cells into the adjacent granulosa cells, where they are converted to estrogens by aromatase, the activity of which is stimulated by FSH (
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During the luteal phase of the cycle, far too much progesterone is formed for all of it to be converted, which accounts for the large secretion of progesterone into the circulating blood at this time. Also, about one fifteenth as much testosterone is secreted into the plasma of the female by the ovaries as is secreted into the plasma of the male by the testes
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Estrogens and Progesterone Are Transported in the Blood Bound to Plasma Proteins. Both estrogens and progesterone are transported in the blood bound mainly with plasma albumin and with specific estrogen- and progesterone-binding globulins. The binding between these hormones and the plasma proteins is loose enough that they are rapidly released to the tissues over a period of 30 minutes or so.
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Functions of the Liver in Estrogen Degradation. The liver conjugates the estrogens to form glucuronides and sulfates, and about one fifth of these conjugated products is excreted in the bile; most of the remainder is excreted in the urine. Also, the liver converts the potent estrogens estradiol and estrone into the almost totally impotent estrogen estriol. Therefore, diminished liver function actually increases the activity of estrogens in the body, sometimes causing hyperestrinism.
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Fate of Progesterone. Within a few minutes after secre- tion, almost all the progesterone is degraded to other steroids that have no progestational effect. As with the estrogens, the liver is especially important for this meta- bolic degradation. The major end product of progesterone degradation is pregnanediol. About 10 percent of the original progester- one is excreted in the urine in this form. Therefore, one can estimate the rate of progesterone formation in the body from the rate of this excretion
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FUNCTIONS OF THE ESTROGENS— THEIR EFFECTS ON THE PRIMARY AND SECONDARY FEMALE SEX CHARACTERISTICS A primary function of the estrogens is to cause cellular proliferation and growth of the tissues of the sex organs and other tissues related to reproduction
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Effect of Estrogens on the Uterus and External

Female Sex Organs. During childhood, estrogens are secreted only in minute quantities, but at puberty, the quantity secreted in the female under the influence of the pituitary gonadotropic hormones increases 20-fold or more. At this time, the female sex organs change from those of a child to those of an adult. The ovaries, fallopian tubes, uterus, and vagina all increase several times in size. Also, the external genitalia enlarge, with deposition of fat in the mons pubis and labia majora and enlargement of the labia minora

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In addition, estrogens change the vaginal epithelium from a cuboidal into a stratified type, which is consider- ably more resistant to trauma and infection than is the prepubertal cuboidal cell epithelium. Vaginal infections in children can often be cured by the administration of estrogens simply because of the resulting increased resis- tance of the vaginal epithelium
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Estrogens cause marked proliferation of the endometrial stroma and greatly increased development of the endometrial glands, which will later aid in providing nutrition to the implanted ovum. These effects are dis- cussed later in the chapter in connection with the endo- metrial cycle
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Effect of Estrogens on the Fallopian Tubes. The estrogens’ effects on the mucosal lining of the fallopian tubes are similar to their effects on the uterine endome- trium. They cause the glandular tissues of this lining to proliferate, and especially important, they cause the number of ciliated epithelial cells that line the fallo- pian tubes to increase. Also, activity of the cilia is con- siderably enhanced. These cilia always beat toward the uterus, which helps propel the fertilized ovum in that direction
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Effect of Estrogens on the Breasts. The primordial breasts of females and males are exactly alike. In fact, under the influence of appropriate hormones, the mascu- line breast during the first 2 decades of life can develop sufficiently to produce milk in the same manner as the female breast. Estrogens cause (1) development of the stromal tissues of the breasts, (2) growth of an extensive ductile system, and (3) deposition of fat in the breasts. The lobules and alveoli of the breast develop to a slight extent under the influence of estrogens alone, but it is progesterone and prolactin that cause the ultimate determinative growth and function of these structures. In summary, the estrogens initiate growth of the breasts and of the milk-producing apparatus. They are also responsible for the characteristic growth and external appearance of the mature female breast. However, they do not complete the job of converting the breasts into milk-producing organs
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Effect of Estrogens on the Skeleton. Estrogens inhibit osteoclastic activity in the bones and therefore stimulate bone growth. As discussed in Chapter 80, at least part of this effect is due to stimulation of osteoprotegerin, which is also called osteoclastogenesis inhibitory factor, a cyto- kine that inhibits bone resorption. At puberty, when the female enters her reproductive years, her growth in height becomes rapid for several years. However, estrogens have another potent effect on skeletal growth: They cause uniting of the epiphyses with the shafts of the long bones. This effect of estrogen in the female is much stronger than the similar effect of testos- terone in the male. As a result, growth of the female usually ceases several years earlier than growth of the male. A female eunuch who is devoid of estrogen produc- tion usually grows several inches taller than a normal mature female because her epiphyses do not unite at the normal time
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Osteoporosis of the Bones Caused by Estrogen Deficiency in Old Age. After menopause, almost no estrogens are secreted by the ovaries. This estrogen defi- ciency leads to (1) increased osteoclastic activity in the bones, (2) decreased bone matrix, and (3) decreased deposition of bone calcium and phosphate. In some women this effect is extremely severe, and the resulting condition is osteoporosis, described in Chapter 80. Because osteoporosis can greatly weaken the bones and lead to bone fracture, especially fracture of the vertebrae, many postmenopausal women are treated prophylactically with estrogen replacement to prevent the osteoporotic effects
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Estrogens Slightly Increase Protein Deposition. Estro- gens cause a slight increase in total body protein, which is evidenced by a slight positive nitrogen balance when estrogens are administered. This effect mainly results from the growth-promoting effect of estrogen on the sexual organs, the bones, and a few other tissues of the body. The enhanced protein deposition caused by testos- terone is much more general and much more powerful than that caused by estrogens
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Estrogens Increase Body Metabolism and Fat Depo- sition. Estrogens increase the whole-body metabolic rate slightly, but only about one third as much as the increase caused by the male sex hormone testosterone. Estrogens also cause deposition of increased quantities of fat in the subcutaneous tissues. As a result, the percentage of body fat in the female body is considerably greater than that in the male body, which contains more protein. In addition to deposition of fat in the breasts and subcutaneous tissues, estrogens cause the deposition of fat in the but- tocks and thighs, which is characteristic of the feminine figure.
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Estrogens Have Little Effect on Hair Distribution.

Estrogens do not greatly affect hair distribution. However, hair does develop in the pubic region and in the axillae after puberty. Androgens formed in increased quantities by the female adrenal glands after puberty are mainly responsible for this development of hair

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Effect of Estrogens on the Skin. Estrogens cause the skin to develop a texture that is soft and usually smooth, but even so, the skin of a woman is thicker than that of a child or a castrated female. Estrogens also cause the skin to become more vascular, which is often associated with increased warmth of the skin and also promotes greater bleeding of cut surfaces than is observed in men
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Effect of Estrogens on Electrolyte Balance. The chemical similarity of estrogenic hormones to adrenocor- tical hormones has been pointed out. Estrogens, like aldo- sterone and some other adrenocortical hormones, cause sodium and water retention by the kidney tubules. This effect of estrogens is normally slight and rarely of signifi- cance, but during pregnancy the tremendous formation of estrogens by the placenta may contribute to body fluid retention
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FUNCTIONS OF PROGESTERONE Progesterone Promotes Secretory Changes in the Uterus. A major function of progesterone is to promote secretory changes in the uterine endometrium during the latter half of the monthly female sexual cycle, thus prepar- ing the uterus for implantation of the fertilized ovum. This function is discussed later in connection with the endometrial cycle of the uterus. In addition to this effect on the endometrium, proges- terone decreases the frequency and intensity of uterine contractions, thereby helping to prevent expulsion of the implanted ovum
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Effect of Progesterone on the Fallopian Tubes. Pro gesterone also promotes increased secretion by the mucosal lining of the fallopian tubes. These secre- tions are necessary for nutrition of the fertilized, divid- ing ovum as it traverses the fallopian tube before implantation
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Progesterone Promotes Development of the Breasts. Progesterone promotes development of the lobules and alveoli of the breasts, causing the alveolar cells to prolifer- ate, enlarge, and become secretory. However, progester- one does not cause the alveoli to secrete milk; as discussed in Chapter 83, milk is secreted only after the prepared breast is further stimulated by prolactin from the anterior pituitary gland. Progesterone also causes the breasts to swell. Part of this swelling is due to the secretory development in the lobules and alveoli, but part also results from increased fluid in the tissue
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