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The Black Swan Theory. 1) The event is a surprise (to the observer) 2) The event has a major effect.
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The Black Swan Theory 1) The event is a surprise (to the observer) 2) The event has a major effect. 3) After the first recorded instance of the event, it is rationalized by hindsight, as if it could have been expected; that is, the relevant data were available but unaccounted for in risk mitigation programs. The same is true for the personal perception by individuals
The disproportionate role of high-profile, hard-to-predict, and rare events that are beyond the realm of normal expectations in history, science, finance, and technology • The non-computability of the probability of the consequential rare events using scientific methods (owing to the very nature of small probabilities)
The psychological biases that make people individually and collectively blind to uncertainty and unaware of the massive role of the rare event in historical affairs • Unlike the earlier philosophical "black swan problem," the "black swan theory" refers only to unexpected events of large magnitude and consequence and their dominant role in history. Such events, considered extreme outliers, collectively play vastly larger roles than regular occurrences
Carneus Mole • Synonym for fleshy mole ... • A uterine mass occurring • after fetal death and • consisting of blood clots, • fetal membranes, and placenta • . ... Synonym: blood moles
Breus Mole • Maternal blood dissects from the deciduavera around the placental villi and migrates to the subchorionic region of the chorionic plate on the fetal surface of the placenta • A large proportion of cases end in abortion or fetal death. Most remaining fetuses develop IUGR and deliver preterm
Partial Hydatidiform Mole • Features of a partial or incomplete molar pregnancy include some element of fetal tissue and hydatidiform changes that are focal and less advanced. There is slowly progressive swelling within the stroma of characteristically avascular chorionic villi, whereas vascular vili that have a functioning fetal-placental circulation are spared
For a Partial mole the karyotype is typically triploid – 69, XXX,69XXY, or much less commonly, 69,XYY. These are each composed of one maternal and two paternal haploid sets of chromosome. Only 3 of 270 molar pregnancies studied were tetraploid. The nonviable fetus associated with a triploid partial mole typically has multiple malformations. In another study, 82% of fetuses had symmetrical growth restriction.
The risk of persistent trophoblastic disease after a partial mole is substantially lower than that following a complete molar preganancy. Moreover, persistent disease seldom is choriocarcinoma. 0.1% of partial moles are complicated by choriocarcinoma.
Higher postevacuation Beta-hCG levels correlated with increased risk for persistent disease. Specifically, levels >= 200 mIU/mL in the third through eighth week postevacuation were associated with at least a 35% risk of persistent disease.
Twin Molar Pregnancy • a twin gestation composed of a complete diploid molar pregnancy and a normal pregnancy is not rare. 5% of diploid moles were part of a twin pregnancy with a fetus. Survival of the normal coexisting fetus is variable and depends on whether the diagnosis is made, if so, whether problems from the molar component such as preeclampsia or hemorrhage develop.
Twin Molar Pregnancy • 45% progressed to 28 weeks and of these 70% of neonates survived. • A normal placenta supplies nutrition to one twin , and the co-pregnancy is a complete molar gestation. Optimal management is uncertain, but preterm delivery is frequently required because bleeding or severe preeclampsia.
Twin Molar Pregnancy • Compared with partial mole, women with these types of twin pregnancies have a substantive risk of developing subsequent gestational trophoblasticneoplasia. This risk does not appear greater than following a singleton complete mole. 21% of pregnancies not terminated subsequently required chemotherapy for persistent disease.
Twin Molar Pregnancy • This rate is not significantly different from the rate of 16% among women who terminate their pregnancies. In another series 25% of such twin pregnancies subsequently needed chemotherapy
Bandl’s Ring • Localized rings or constrictions of the uterus develop in association with prolonged obstructed labor that are seldom encountered today. The pathological retraction ring of Bandl is associated with marked stretching and thinning of the lower uterine segment. The ring may be seen clearly as a uterine indentation and signifies impending rpture of the lower uterine segment.
Bandl’s Ring • Following birth of a first twin, a pathological ring may still develop occasionally as hourglass constrictions of the uterus. The ring can sometimes be relaxed and delivery effected with appropriate general anesthesia, but occasionally prompt cesarean delivery offers a better prognosis for the second twin.
Chromosomal Microdeletions • Some deletions are not large enough to be recognized by traditional karyotyping and thus, molecular cytogenetic techniques are required….These deletions cause clinically recognizable syndromes that my include serious but unrelated phenotypic abnormalities. Deletions can occur in any region, however, several are found more frequently than expected by chance alone. This is thought to result from a greater propensity for certain regions to break.
Microarray • A DNA microarray (also commonly known as DNA chip or (biochip) is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to genotype multiple regions of a genome. Each DNA spot contains picomoles (10−12 moles) of a specific DNA sequence, known as probes (or reporters or oligos).
MICROARRAY • These can be a short section of a gene or other DNA element that are used to hybridize a cDNA or cRNA (also called anti-sense RNA) sample (called target) under high-stringency conditions. Probe-target hybridization is usually detected and quantified by detection of flourophor-, silver-, or chemiluminecence-labeled targets to determine relative abundance of nucleic acid sequences in the target.
The Microarray • Since an array can contain tens of thousands of probes, a microarray experiment can accomplish many genetic tests in parallel. • In standard microarrays, the probes are synthesized and then attached via surface engineering to a solid surface by a covalent bond to a chemical matrix • Specific arrays are designed to find sequences of bases which have been identified with specific chromosomal deletion areas in human disease
Wolf-Hirschorn Syndrome • Wolf-Hirschhorn syndrome (WHS) refers to a condition that is caused by a missing part (deletion) of the short arm of chromosome 4. This missing genetic material results in severe developmental delays, a characteristic facial appearance, and may include a variety of other birth defects. • Some patients who have WHS may have a small deletion on 4p, while others may be missing up to half of 4p. For this reason, some individuals have a less severe case of WHS than others do. The band 4p16.3 needs to be deleted in order for an individual to have full expression of WHS.
Wolf-Hirschorn Syndrome • WHS frequently presents prenatally with slow growth (intrauterine growth delays). Some infants with WHS can be stillborn or die shortly after birth. As many as one-third of reported patients have died in the first year of life. Individuals with WHS have been described as having a characteristic facial appearance likened to a “Greek Helmet facies.” This can be described as having a small head size (microcephaly), eyes spaced widely apart (ocular hypertelorism), downturned mouth, short upper lip and short groove between the upper lip and nose (philtrum) or bilateral cleft lip and small chin (micrognathia).
Wolf-Hirschorn Syndrome • These children have severe developmental delays. Other significant problems can include heart defects, cleft lip and/or palate, hearing impairment, and eye problems. Most children who have WHS have seizures (approximately 90%). Seizures are one of the major health concerns in children with WHS. These seizures begin between five and 23 months of age, however approximately 50% of the individuals stop having seizures between age three and 11. Sleeping problems are also common in children who have WHS. Although it seems that most of the literature focuses on children who have WHS, there are adults who have WHS.
De Novo Deletion • Approximately 85–90% of cases of WHS occur as the result of a new deletion in the affected individual. This is also known as a de novo deletion and simply means that the affected individual’s parents did not have any chromosome arrangement that led to the deletion. In this case, the chance for recurrence in future pregnancies of a couple whom has an affected child is not increased. In the remaining 10–15% of cases, one of the parents of the affected individual carries a balanced translocation.
Balanced Translocation • When a parent is identified as being a carrier of a balanced translocation, with each pregnancy they have an increased chance for having a child with an unbalanced chromosome arrangement. The chance of this is determined by the individual’s specific translocation, how it was identified, and which parent is the carrier of the translocation. Genetic counseling should be offered for any family in which a child is diagnosed to have WHS. Other family members should also be offered counseling and chromosome analysis to determine if they are carriers of a balanced translocation.
Angelman Syndrome • dysmorphicfacies – “happy puppet” appearance, mental retardation, ataxia, hypotonia and seizures. 15q11.2q13 (maternal genes). • normal stature and weight severe mental retardation absent speech seizure disorder ataxia and jerky arm movements Paroxysms of inappropriate laughter In about 70% of cases, Angelman’s is caused by a microdeletion of disruption of the maternal 15q11-q13. In 2%, the syndrome is caused by paternal uniparentaldisomy; and another 2-3 % are due to imprinting with the maternal genes activated.
UniparentalDisomy • both members of one pair of chromosomes are inherited from the same parent, instead of one member being inherited from each parent. Often, uniparentaldisomy does not have clinical consequences. Some exceptions are when it involves chromosomes 6, 7, 11, 14, 15. These offspring are at increased risk for an abnormality tht results from parent-of-origin differences in gene expression. Although several genetic mechanisms may cause uniparentaldisomy, the most common is ‘trisomic rescue’. After a nondisjunction event produces a trisomicconceptus, one of the three homologues may be lost. This may result in uniparentaldisomy for that chromosomes in a third of cases.
IMPRINTING • a process by which certain genes are inherited in an inactivated or transcriptionally silent state at one of the parental loci in the offspring. This type of gene inactivation is determined by the gender of the transmitting parent and may be reversed in the next generation. Imprinting affects gene expression by epigenetic control; that is, it changes the phenotype by altering gene expression and not by permanently altering the genotype. When a gene is inherited in an imprinted state, gene function is directed by the co-gene inherited from the other parent, so imprinting exerts an effect by controlling the dosage of specific genes.
Imprinting • Selected diseases can involve imprinting. Two very different diseases that may be caused by, uniparentaldisomy, or imprinting for the 15q11-q13 region of DNA are Prader-Wili Syndrome and the Angelman Syndrome.
Prader-Willi Syndrome • obesity and hyperphagia short stature small hands and feet small external genitalia mild mental retardation • In over 70% of cases, Prader-Willi is caused by microdeletion or disruption for the paternal 15q11-q13. The remainder of cases are due to imprinting with the paternal genes inactive.
External Parasitic Twins • Grossly defective fetus or merely fetal parts attached externally to a relatively normal twin. The parasitic twin usually consists of supernumerary limbs, often with some viscera. Classically, a heart and brain are absent. Attachment mirrors those sites described for conjoined twins. Parasites are believed to result from the demise of the defective twin, with its surviving tissue attached to and vascularized by its normal twin.
