what is placenta dysplasia

n* Context.--Placental mesenchymal dysplasia is characterized by placentomegaly and may be mistaken for molar pregnancy both clinically and macroscopically because of the presence of ""grapelike vesicles."" It may be associated with a completely normal fetus, a fetus with growth restriction, or a fetus with features of Beckwith-Wiedemann syndrome.

Placental mesenchymal dysplasia.

"Placental mesenchymal dysplasia. Link/Page Citatio

Objective.--To review the etiology, molecular pathology, gross and microscopic features, clinical presentation, complications, and differential diagnosis of placental mesenchymal dysplasia. Data Sources.--The Pub Med and the Medline databases were systematically searched for articles between 1970 and 2006. The following keywords were used: placental mesenchymal dysplasia, mesenchymal hyperplasia, molar pregnancy, pseudomolar pregnancy, Beckwith-Wiedemann syndrome, and placentomegaly. Relevant references from review articles were also searched. Conclusions.--Placental mesenchymal dysplasia should be considered in the differential diagnosis when the ultrasonographic findings show a cystic placenta. Close attention should be paid to fetal morphology for early recognition of fetal complications and to prevent unnecessary termination of pregnancy in cases associated with a normal fetus. ********** Placental mesenchymal dysplasia (PMD) is a relatively recently recognized, rare placental vascular anomaly characterized by placentomegaly and grapelike vesicles resembling partial molar pregnancy by ultrasonography and by gross placental examination. Placental mesenchymal dysplasia was initially described by Moscoso et al (1) as stem villous hyperplasia in 1991 when they identified 2 cases with elevated maternal serum alpha fetoprotein levels and enlarged placentas with corresponding ultrasonographic features suggestive of partial mole. There were aneurysmally dilated vessels on the fetal surfaces of the placentas and dilated stem villi filled with clear gelatinous material in the subchorionic region. Histologically, however, these placentas could be distinguished from partial moles because of the absence of trophoblastic proliferation. (1) Since then, this entity is being increasingly recognized. Several authors have preferred to use the term placental mesenchymal hyperplasia rather than dysplasia. (2-5) The true incidence of PMD is unknown because it has been previously reported under a variety of names such as ""placentomegaly with massive hydrops of placental stem villi"" and ""pseudopartial moles."" (6,7) In addition, PMD remains unfamiliar to many pathologists and for these reasons it is believed that PMD is both underdiagnosed and underreported. According to 1 publication, the incidence of PMD is 0.02%. (8) To date, 66 cases of PMD have been reported in the literature with a definite female preponderance of 3.6:1 (female-male). (9) This review intends to highlight the salient features of PMD and the importance of distinguishing PMD from its mimickers, the most important of which is a partial mole. Placental mesenchymal dysplasia is associated with Beckwith-Wiedemann syndrome (BWS) and fetal growth restriction in the majority of the cases but can also be associated with normal-appearing fetuses. Placental mesenchymal dysplasia should be included in the differential diagnosis of cystic lesions of a placenta by sonography especially when a phenotypically normal-appearing fetus can be identified. ETIOLOGY The underlying cause of PMD is currently unknown. Some speculate that PMD is a congenital malformation of the mesoderm. This theory is based on observations of mesenchymal hyperplasia in stem villi along with other placental mesenchymal proliferative disorders such as chorangiomas and chorionic vessel dilatation as well as hemangiomas of the fetus. (2) In addition, the enlarged stem villi contain acid mucopolysaccharide, which is found in the connective tissue layers of the normal chorionic mesoderm. (2) There is a definite association of PMD with BWS, which is characterized by macrosomia, exomphalos, macroglossia, omphalocele, and internal visceromegaly in addition to placentomegaly and increased susceptibility to childhood tumors. (6,10) According to a recent article, 23% of PMD cases are associated with BWS. (9) Because of highly variable penetrance in BWS, PMD and BWS are considered a spectrum of phenotypic changes of common etiology. At one end of the spectrum, PMD exhibits phenotypic changes limited to the placenta and BWS at the opposite end with phenotypic changes affecting both placenta and fetus. The molecular pathogenesis of BWS has been extensively studied and there is strong evidence that abnormal expression or disruption of 1 or more of the imprinting gene (s) on chromosome 11p15.5 (the so-called BWS candidate gene) is thought to be the major underlying defect. (7,11) Hypoxia and hypoperfusion of unknown etiology may give rise to the phenotypic findings in the placenta with PMD. During hypoxia, fibroblasts are stimulated to produce increased connective tissue fibers with subsequent increased production of vascular endothelial growth factor by villous macrophages leading to angiogenesis. (12) More recently, androgenetic/biparental mosaicism has been suggested by Kaiser-Roger et al (13) as the underlying cause of PMD, supported by the finding of 2 separate cell lines in PMD placental tissue. In this condition, the androgenetic cell line is thought to arise from endoreduplication of the haploid paternal genome, whereas the biparental cell line arises from the combination of the haploid maternal and the paternal genomes. However, the presence of the same paternal haploid complement in both cell lines suggests paternal uniparental isodisomy and involvement of only a single egg and sperm nucleus. (13) The abnormal androgenetic cells are confined to chorionic mesoderm, membranes, and vessels, whereas the trophoblastic cells are normal with no evidence of androgenetic cells. (13) This explains the absence of trophoblast overgrowth in PMD in contrast to complete moles in which androgenetic cells are identified in the trophoblastic cell layer. Studies have shown a female predominance in cases of PMD and it is speculated that there is a relationship to the X chromosome, although an exact underlying mechanism is not yet fully known. (8) Female predominance can also be explained by androgenetic/biparental mosaicism. (13) Because the androgenetic cell line has arisen from duplication of the haploid paternal genome, it is likely this would give rise to the 46,XX cell line because 46,YY cell lines are incompatible with life. (13) However, because cases of PMD with male fetuses have been reported, it seems that the etiology of PMD is heterogenous. MOLECULAR PATHOGENESIS Placental mesenchymal dysplasia is characterized by overgrowth of placental tissue. The mechanisms for this overgrowth are only partially understood at this time. Chen et al (2) analyzed DNA from the fetus and different parts of the placenta from 2 cases of PMD and confirmed genetic identity among the chorangioma, vesicle-like villi, and the fetus. Much of the information on the molecular genetics of PMD comes from studies done on BWS cases and it is thought that defects in the genes controlling cell cycle lead to overgrowth of placental tissue and are described here briefly. Imprinted Genes Cluster at Chromosome 11p15.5 Beckwith-Wiedemann syndrome imprinting genes cluster is traced to chromosome 11p15.5 with disruption of 1 or more genes. (14) The most commonly involved genes are CDKN1C ( [p57.sup. KIP2]), H19, IGF-II, and KVLQT. There have been no major analyses of how frequently these molecular alterations are observed in PMD, but it is thought that, in PMD without fetal anomalies, the underlying 11p15 abnormality is confined to the placenta. The genomic imprinting of these genes is influenced by parent of origin. The CDKN1C ( [p57.sup. KIP2]) gene is expressed in the maternal genome, whereas the paternal allele is transcriptionally silent. (15) It belongs to the family of cell-cycle regulators and encodes a cyclin dependent kinase inhibitor. The underlying abnormality is thought to be the loss of activity of the [p57.sup. KIP2] gene causing loss of cell-cycle inhibition and overgrowth. (16,17) Insulin-like growth factor II (IGF-II) encodes a fetal-specific growth factor that is paternally expressed. (18) It has been suggested that abnormalities of IGF-II gene or IGF-II receptor gene lead to up-regulation of IGF-II resulting in overgrowth of the placental tissue. (19,20) Molecular studies have shown that IGF-II overproduction is the result of an aberration in normal maternal suppression or, in rare cases, because of the presence of 2 paternal copies of the IGF-II gene. (7) It is suggested that IGF-II and [p57.sup. KIP2] act in the same pathway but in an opposing manner to control the cell cycle. A gain in function of IGF-II or a loss in the function of [p57.sup. KIP2] would have similar consequences, that is, somatic overgrowth. (21) Vascular Endothelial Growth Factors Vascular endothelial growth factors (VEGFs) have a major role in normal angiogenesis. The VEGF-D gene is encoded on chromosome Xp22.31 and because of the predominance of female fetuses affected by PMD, some authors have suggested a relationship between abnormal angiogenesis and chromosome X. (8) This relationship has not been confirmed or studied by other investigators. Vascular endothelial growth factors interact with tyrosine kinase receptors on the endothelial cell surfaces. Flt-4, a tyrosine kinase receptor expressed on placental endothelial cells, interacts with VEGF-C and, because of structural similarities between VEGF-C and VEGF-D, Flt-4 may also interact with VEGF-D. (22,23) It is quite possible that this interaction causes increased angiogenesis and may play a role in the development of vascular malformations seen in PMD. CLINICAL PRESENTATION There is no specific clinical symptomatology associated with PMD. Most cases of PMD in early pregnancy are diagnosed by prenatal ultrasonography done either for routine prenatal checkup or because of an abnormal amniocentesis result. The most common abnormal laboratory test includes increased level of maternal serum alpha fetoprotein, which is thought to be of fetal origin. It is speculated that the increase in the surface transfer area because of increased placental volume and increased vessels within the stem villi may lead to increased transfer of alpha fetoprotein into the maternal circulation. (1) The level of [beta]-human chorionic gonadotropin is normal to slightly increased but returns to normal levels soon after delivery. (7,9) Later in the pregnancy, the patient usually presents with intrauterine growth restriction or fetal demise. Patients may also present with polyhydramnios if the fetus has swallowing difficulty as part of BWS. Many cases are asymptomatic and are diagnosed postpartum because of delivery of an abnormally large placenta. The sonographic features of PMD are very similar to those of partial moles. (1) A thickened placenta with hypoechoic spaces are classical sonographic findings of both PMD and molar pregnancies. The other differential diagnoses of these ultrasonographic findings include chorioangiomas and subchorionic hematomas. However, these finding are less diffuse than in PMD. (24) A few small anechoic spaces can be present in the placental tissue without any clinical significance. (25) However, if the process is diffuse, close monitoring of the pregnancy is required. Jauniaux et al (10) evaluated 6 suspected cases of PMD with serial prenatal ultrasonography and Doppler imaging that showed cystic spaces located deep in the placental parenchyma and increased placental thickness early in gestation. As the pregnancy advanced, the cystic spaces moved toward the chorionic plate. The chorionic plate vessels, including both the arteries and veins, became progressively dilated and aneurysmal. No abnormal chorionic vessels were seen before midgestation. The ultrasonographic finding of a large cystic placenta along with phenotypically well-formed fetus is highly unlikely in molar pregnancy and should raise the possibility of PMD. MACROSCOPIC FEATURES Grossly, the placenta is usually extremely large for gestational age. In the cases described so far, more than 90% of the cases exhibited placental weights of more than the 90th percentile. (9) The gross placental findings in PMD vary with gestational age. In third trimester PMD placenta, the chorionic plate vessels are aneurysmally dilated and tortuous (Figure 1, A and B), measuring up to 2.5 cm in diameter, and show abnormal branching. (7) The dilated chorionic plate vessels may show luminal thrombosis or can rupture giving rise to subamniotic hemorrhage, which can further compromise the growth restricted fetus. (3,7) In both early and late gestation PMD, placental parenchyma may have pale and friable areas with streaks of prominent stem villi and multiple cysts oriented perpendicular to the chorionic plate. (9) These grapelike cystic vesicles, which are similar grossly to those of molar pregnancy, range in size from 0.3 to 2.5 cm and are usually visible grossly (Figure 2, A and B). In rare cases, the vesicle formation is minimal or absent. (3) In cases terminated before 20 weeks of gestation, the chorionic plate vessels are not dilated and the normal and abnormal areas are not clearly delineated suggesting that the vascular malformations develop progressively secondary to circulatory imbalance and poor vascularization of the dysplastic villi. (10) As the pregnancy advances, tangled congested vessels grossly resembling gray-white or dark-red wormlike structures may be identified within the parenchyma (Figure 2, A and B) and are often most prominent in the subchorionic plate region near the fetal surface. (26,27) Amniotic bands have also been described in rare cases. (28) [FIGURES 1-2 OMITTED] MICROSCOPIC FEATURES Despite its resemblance to partial moles on gross examination, PMD can be distinguished from the former by careful histologic examination. The histopathologic findings in placentas with PMD are similar irrespective of fetal association with BWS and vary with the gestational age. Third trimester PMD placentas have dilated thick-walled chorionic plate vessels with fibromuscular hyperplasia and may have fresh or organizing thrombi (Figure 3, A) with varying degrees of luminal obliteration. (27,29) Thrombosis may be present in both the veins and arteries of the chorionic plate. (3) The vessel walls usually show some degree of fibrinoid necrosis (Figure 3, B). The parenchymal vascular malformations show dilated vessels and may have fresh or organizing thrombosis (Figure 3, C). The stem villi are enlarged in both early and late gestation PMD placentas and, at times, may be up to 10 times the size of normal stem villi late in gestation. These enlarged stem villi have central cisterns filled with gelatinous material and fibromuscular vessels at the periphery (Figure 4, A). (27) These thick-walled vessels develop during time as pregnancy advances and may show fibrinoid necrosis and degenerative changes in the vessel wall (Figure 4, B). Irrespective of gestational age, the stem villi in PMD have loose and myxoid stroma with an overgrowth of fibroblasts (Figure 4, B) and foci of myxoid degeneration unlike the normal stem villi, which are mostly fibrous. (1,27) Similar to the stem villi, the terminal villi may also show mesenchymal cell hypercellularity and stromal fibrosis (Figure 4, C). (8,26) However, scattered between dilated stem villi may be a mixture of normal-appearing and hydropic secondary and tertiary villi. (8,9) Early in gestation these changes are not as well-developed and the stem villi show dilated cisterns surrounded by loose myxomatous stroma, which has delicate vessels under the trophoblastic layer (Figure 5, A and B). Some stem villi reveal intravillous fibrin deposition and lack distinct fetal vessels because of fetal vessel thrombosis. (3) Recanalization of stem villus thrombosed vessels has also been described. (8) The important diagnostic features of PMD include the absence of trophoblastic proliferation, stromal trophoblastic inclusions, and scalloping of the villous surface, which are characteristics of a molar pregnancy. (3,27,30) The vascular pattern in the hydropic villi in PMD range from normal to chorangiomatous or myxoangiomatous to decreased or obliterated vasculature. (1,7,9,26,28) Discrete chorangiomas may be identified. (31) In rare cases, extramedullary hematopoiesis is identified. Nucleated red cells are seen mostly in areas of chorangiosis/ chorangiomas at a stage when nucleated red cells are not normally seen in the fetal vessels. These changes are thought to represent a consequence of placental hypoxia. (7) Villous hemorrhage has been identified in some cases. (8) [FIGURES 3-5 OMITTED] IMMUNOHISTOCHEMICAL AND SPECIAL STAINS Stromal cells in the large stem villi of PMD placentas are positive for vimentin and desmin and negative for alpha-smooth muscle actin, whereas the stromal cells in the surrounding normal-appearing stem villi are positive for vimentin, desmin, and [alpha]-smooth muscle actin. (27) In a normally developing placenta, mesenchymal cells (stromal cells in the villi) acquire vimentin and desmin at the end of the second month of gestation, at which stage these cells are called reticular cells or fibroblasts. With further cell differentiation, these fibroblasts would acquire alpha-smooth muscle actin and would then be called myofibroblasts. In PMD, the staining characteristics of the dilated stem villi stromal cells is that of fibroblasts and it appears that these cells cease to differentiate beyond the fibroblast stage. (32) The ground substance shows a strong reaction to Alcian blue stains indicating the presence of large amounts of acid mucopolysaccharides. (27) Macrophages in the stroma also contain Alcian blue positive vacuoles in their cytoplasm. (1) The [p57.sup. KIP2] protein is a potential marker that may prove helpful in distinguishing PMD from molar pregnancy. Castrillon et al (33) utilized the [p57.sup. KIP2] diagnostic marker to distinguish normal placental tissue, spontaneous abortion with hydropic changes, and partial moles from complete molar pregnancies. Unfortunately, there have been no studies done to see the utilization of this marker in PMD, but, with increased awareness of PMD, it is hoped that studies in the future will demonstrate the significance of this marker. CYTOGENETICS AND DNA PLOIDY STUDIES In the cases described in which karyotyping has been performed, the majority of the cases are diploid. (26) Most are karyotypically and phenotypically normal females (46,XX). With rare exceptions, no major chromosomal abnormalities are identified. (29) Four cases described exhibited chromosomal abnormalities including trisomy 13, Klinefelter syndrome (47,XXY), triploidy (69,XXX), and 46,XXp-. (7-9) In contrast to PMD, the majority of the partial moles are triploid. DNA ploidy studies and karyotyping can be performed utilizing cytogenetics, image analysis, flow cytometry, or fluorescent in situ hybridization on either fresh or fixed tissue. DNA ploidy studies may not be very helpful in distinguishing PMD from complete moles or spontaneous abortions with hydropic changes because most of these cases will have a diploid karyotype. DIFFERENTIAL DIAGNOSIS It is important to distinguish PMD from molar pregnancy because it may avoid unnecessary termination of pregnancy especially if prenatal ultrasonographic examination shows features suggestive of molar pregnancy in the presence of a normal-appearing fetus. The main differential diagnoses of PMD, both clinically and pathologically, are partial hydatidiform moles, a twin gestation with complete mole, spontaneous abortion with hydropic changes, and confined placental mosaicism. Unlike partial moles, the placenta in PMD is almost always diploid (except in rare instances), and histologically the villi do not show proliferation of trophoblasts or stromal trophoblastic inclusions. The triploid fetus associated with a partial mole shows growth restriction with a variety of external and internal defects. In twin gestations with complete moles, the abnormal fetal vessels in the stem villi characteristic of PMD are absent even though the fetus may have a diploid karyotype. Complete hydatidiform moles may also exhibit high levels of IGF-II expression and loss of expression of [p57.sup. KIP2], but these are purely androgenetic and the entire genome is paternally derived. (34) Spontaneous abortion with hydropic change may have vesicle formation and can be confused with early PMD. The vesicles in hydropic spontaneous abortion, if present, are usually small and are not diffuse. Second, the histology of spontaneous abortions shows degenerative changes without the classic histopathologic features of PMD. Cases of confined placental mosaicism involving trisomy 16 have been reported to have cystic villi on ultrasonography, but these cases can be diagnosed accurately by karyotyping both the newborn and the placenta. (35) COMPLICATIONS Placental mesenchymal dysplasia is a rare disease entity, and it is difficult to determine whether the complications faced by these fetuses are true complications of this disease process or merely coincidental findings. Because approximately one fourth of cases of PMD are associated with BWS, some of the complications seen in fetuses born with PMD are secondary to BWS without fully developed phenotypic features. For example, hyperinsulinemic hypoglycemia seen in neonates with PMD is secondary to islet cell hyperplasia of the pancreas, which is a frequent finding in BWS. (36) The common fetal complications reported in phenotypically normal fetuses associated with PMD are prematurity, intrauterine growth restriction, and intrauterine fetal demise. (3,27) Severe intrauterine growth restriction may be related to diversion of fetal blood within the vascular malformations or stem villi blood vessel thrombosis resulting in hypoperfusion and hypoxia that ultimately leads to intrauterine growth restriction. (3) Although many obstetrical complications such as polyhydramnios, fetal hydrops, gestational diabetes, and preeclampsia may be associated with a large placenta, placentomegaly in PMD, in and of itself, is thought not to be the cause of fetal complications. (10) No direct association of placental weight and fetal or maternal complications have been identified. Rather, the complications are thought to be related to the degree of vascularity and excessive vascular shunting into the chorangiomatous areas. (10) Cases associated with chorangiomas are thought to be associated with a higher rate of fetal complications including anemia and thrombocytopenia, which in turn are thought to be secondary to microangiopathic hemolytic anemia because of abnormal shunting of the blood. (2,32) Chromosomal abnormalities may be found in a few fetuses, but most are karyotypically and phenotypically normal females. Rare cases of fetal congenital adrenal hyperplasia, vascular hamartoma, and hepatic mesenchymal hamartoma have been described. (37-39) Phenotypically normal newborns with PMD should be followed up for development of BWS features or other mesenchymal tumors. Follow-up of most of the normal-appearing infants has shown no developmental problems. Maternal complications associated with PMD are comparatively rare. Gestational proteinuric hypertension has been reported, but it is believed that hypertension in these cases is probably a coincidental finding rather than any specific association with PMD. (40) Similarly, polyhydramnios may occur as a result of swallowing-related problems because of macroglossia in a BWS fetus. (36) A 5-year followup of mothers with PMD showed no sign of trophoblastic disease or recurrence of PMD in subsequent pregnancies. (30) However, it should be noted that 15% of BWS cases are familial, and theoretically there is a small increased chance of having recurrence of PMD in such families. CONCLUSIONS Although PMD may be associated with fetal growth restriction or paradoxically with features of overgrowth, it is important to identify these cases prenatally to reduce fetal morbidity and mortality. It is also important to recognize the detailed gross and histopathologic features of this rare disease entity and be able to differentiate this condition from cases presenting as possible partial hydatidiform moles especially in the first half of pregnancy. Prenatal recognition of PMD during early as well as late gestation could prevent unnecessary termination of pregnancy. Placental mesenchymal dysplasia in early pregnancy is more likely to be mistaken for a partial mole especially by ultrasonographic examination. Ultrasonographic findings suggestive of a molar pregnancy because of hypoechoic spaces in the placenta in the presence of an apparently normal fetus, a fetus with growth restriction, or a fetus with features of overgrowth should raise the possibility of PMD. Accepted for publication August 3, 2006. References (1.) Moscoso G, Jauniaux E, Hustin J. Placental vascular anomaly with diffuse mesenchymal stem villous hyperplasia: a new clinico-pathological entity? Pathol Res Pract. 1991;187:324-328. (2.) Chen CP, Chern SR, Wang TY, Huang ZD, Huang MC, Chuang CY. Pregnancy with concomitant chorangioma and placental vascular malformation with mesenchymal hyperplasia. Hum Reprod. 1997;12:2553-2556. (3.) Kuwabara Y, Shima Y, Araki T, Shin S. Mesenchymal stem villous hyperplasia of the placenta and fetal growth restriction. Obstet Gynecol. 2001;98:940-943. (4.) Laberge JM, Patenaude Y, Desilets V, et al. Large hepatic mesenchymal hamartoma leading to mid-trimester fetal demise. Fetal Diagn Ther. 2005;20:141-145. (5.) Hojberg KE, Aagaard J, Henriques U, Sunde L. Placental vascular malformation with mesenchymal hyperplasia and a localized chorioangioma: a rarity simulating partial mole. Pathol Res Pract. 1994;190:808-813. (6.) Lage JM. Placentomegaly with massive hydrops of placental stem villi, diploid DNA content and fetal omphaloceles: possible association with Beckwith-Wiedemann syndromes. Hum Pathol. 1991;22:591-597. (7.) Paradinas FJ, Sebire NJ, Fisher RA, et al. Pseudo-partial moles: placental stem vessel hydrops and the association with Beckwith-Wiedemann syndrome and complete moles. Histopathology. 2001;39:447-454. (8.) Arizawa M, Nakayama M. Suspected involvement of the X chromosome in placental mesenchymal dysplasia. Cong Anomal. 2002;42:309-317. (9.) Cohen MC, Roper EC, Sebire NJ, Stanek J, Anumba DOC. Placental mesenchymal dysplasia associated with fetal aneuploidy. Prenat Diagn. 2005;25:187-192. (10.) Jauniaux E, Nicolaides KH, Hustin J. Perinatal features associated with placental mesenchymal dysplasia. Placenta. 1997;18:701-706. (11.) Maher ER, Reik W. Beckwith-Wiedemann syndrome: imprinting in clusters revisited. J Clin Invest. 2000;105:247-252. (12.) Fox H. Fibrosis of placental villi. J Pathol Bacteriol. 1968;95:573-579. (13.) Kaiser-Rogers KA, Mc Fadden DE, Livasy CA, et al. Androgenetic/ biparental mosaicism causes placental mesenchymal dysplasia. J Med Genet [serial online]. Available at: http://jmg.bmjjournals.com/cgi/content/abstract/ jmg.2005.033571v1. Accessed December 20, 2005. (14.) Ping AJ, Reeve AE, Law DJ, Young MR, Boehnke M, Feinberg AP. Genetic linkage of Beckwith-Wiedemann syndrome to 11p15. Am J Hum Genet. 1989; 44:720-723. (15.) Matsuoka S, Thompson JS, Edwards MC, et al. Imprinting of the gene encoding a human cyclin-dependent kinase inhibitor, p57KIP2, on chromosome 11p15. Proc Natl Acad Sci U S A. 1996;93:3026-3030. (16.) Hatada I, Ohashi H, Fukushima Y, et al. An imprinted gene p57KIP2 is mutated in Beckwith-Wiedemann syndrome. Nat Genet. 1996;14:171-173. (17.) Bhuiyan ZA, Yatsuki H, Sasaguri T, et al. Functional analysis of the p57KIP2 gene mutation in Beckwith-Wiedemann syndrome. Hum. Genet. 1999;104:205-210. (18.) De Chiara TM, Robertson EJ, Efstratiadis A. Parental imprinting of the mouse insulin-like growth factor II gene. Cell. 1991;64:849-859. (19.) Weksberg R, Shen DR, Fei YL, Song QL, Squire J. Disruption of insulin-like growth factor 2 imprinting in Beckwith-Wiedemann syndrome. Nat Genet. 1993;5:143-150. (20.) Lau MMH, Stewart CEH, Liu Z, Bhatt H, Rotwein P, Stewart CL. Loss of the imprinted Igf2/cation-independent mannose 6-phosphate receptor results in fetal overgrowth and perinatal lethality. Genes Dev. 1994;8:2953-2963. (21.) Zhang P, Liegeois NJ, Wong C, et al. Altered cell differentiation and proliferation in mice lacking p57KIP2 indicates a role in Beckwith-Wiedemann syndrome. Nature. 1997;387:151-158. (22.) Yamada Y, Nezu J, Shimane M, Hirata Y. Molecular cloning of a novel vascular endothelial growth factor, VEGF-D. Genomics. 1997;42:483-488. (23.) Joukov V, Pajusola K, Kaipainen A, et al. A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J. 1996;15:290-298. (24.) Reinhart RD, Wells WA, Harris RD. Focal aneurysmal dilatation of subchorionic vessels simulating chorioangioma. Ultrasound Obstet Gynecol. 1999; 13:147-149. (25.) Katz VL, Blanchard GF, Watson WJ, Miller RC, Chescheir NC. The clinical implications of subchorionic placental lucencies. Am J Obstet Gynecol. 1991; 164:99-100. (26.) Lokan J, Chan YF. Placental mesenchymal dysplasia. Pathology. 2002;34: 375-383. (27.) Ohyama M, Kojyo T, Gotoda H, Sato T, Ijiri R, Tanaka Y. Mesenchymal dysplasia of the placenta. Pathol Int. 2000;50:759-764. (28.) Sander CM. Angiomatous malformation of placental chorionic stem vessels and pseudo-partial molar placentas: report of five cases. Pediatr Pathol. 1993;13: 621-633. (29.) Khong TY. Placental vascular development and neonatal outcome. Semin Neonatol. 2004;9:255-263. (30.) Matsui H, Iitsuka Y, Yamazawa K, et al. Placental mesenchymal dysplasia initially diagnosed as partial mole. Pathol Int. 2003;53:810-813. (31.) Chan YF, Sampson A. Placental mesenchymal dysplasia: a report of four cases with differentiation from partial hydatidiform mole. Aust N Z J Obstet Gynaecol. 2003;43:475-479. (32.) Benirschke K, Kaufmann P. Pathology of the Human Placenta. 4th ed. New York, NY: Springer Verlag; 2000. (33.) Castrillon DH, Sun D, Weremowicz S, Fisher RA, Crum CP, Genest DR. Discrimination of complete hydatidiform mole from its mimics by immunohistochemistry of the paternally imprinted gene product p57KIP2. Am J Surg Pathol. 2001;25:1225-1230. (34.) Chilosi M, Piazzola E, Lestani M, et al. Differential expression of p57Kip2, a maternally imprinted cdk inhibitor, in normal human placenta and gestational trophoblastic disease. Lab Invest. 1998;78:269-276. (35.) Astner A, Schwinger E, Caliebe A, Jonat W, Gembruch U. Sonographically detected fetal and placental abnormalities associated with trisomy 16 confined to the placenta: a case report and review of the literature. Prenat Diagn. 1998; 18:1308-1315. (36.) Cohen MM Jr. Beckwith-Wiedemann syndrome: historical, clinicopathological, and etiopathogenetic perspectives. Pediatr Dev Pathol. 2005;8:287-304. (37.) Furuhashi M, Oda H, Nakashima T. Hydrops of placental stem villi complicated with fetal congenital adrenal hyperplasia. Arch Gynecol Obstet. 2000; 264:101-104. (38.) Gibson BR, Muir-Padilla J, Champeaux A, Suarez ES. Case report: mesenchymal dysplasia of the placenta. Placenta. 2004;25:671-672. (39.) Carta M, Maresi E, Giuffre M, et al. Congenital hepatic mesenchymal hamartoma associated with mesenchymal stem villous hyperplasia of the placenta: case report. J Pediatr Surg. 2005;40:e37-39. (40.) Mc Cowan L, Becroft D. Beckwith-Wiedemann syndrome, placental abnormalities, and gestational proteinuric hypertension. Obstet Gynecol. 1994;83: 813-817. Zahida Parveen, MD; Jane Elaine Tongson-Ignacio, MD; Cory R. Fraser, MD; Jeffery L. Killeen, MD; Karen S. Thompson, MD From the University of Hawaii Pathology Residency Program (Drs Parveen, Tongson-Ignacio, and Fraser) and the Department of Pathology, Kapiolani Medical Center for Women and Children (Drs Killeen and Thompson), Honolulu. Dr Parveen is currently at the University of Florida Health Sciences Center, Jacksonville. Dr Tongson-Ignacio is currently at the University of California, Irvine. The authors have no relevant financial interest in the products or companies described in this article. Reprints: Zahida Parveen, MD, University of Florida Health Sciences Center, Department of Pathology, 655 W 8th St, C#505, Jacksonville, FL 32209 (e-mail: zahipar@yahoo.com). COPYRIGHT 2007 College of American Pathologists No portion of this article can be reproduced without the express written permission from the copyright holder. Copyright 2007 Gale, Cengage Learning. All rights reserved. Please bookmark with social media, your votes are noticed and appreciated: "


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1943 U.S. Copper Cent

1943 U. S. Copper Cent In 1943 the United States Congress voted to make Lincoln cents out of zinc-coated steel. The country was fighting World War II and copper supplies were needed to make cartridge casings for the war effort.

Were any 1943 pennies made of copper? Yes! As we have explained, there shouldn’t have been. An unknown number were made, due to an accident at the mint…To understand how the accident happened, you have to know something about how coins are made. They begin as 10-foot rolls of metal that look like huge paper towel rolls. Coin blanks are cut from these sheets with what looks like a giant cookie cutter. The blanks are then washed and heated and sent through a machine called an Upsetting machine that shapes the edge of each blank, creating the coin rim. Then the blanks are dumped into hoppers that carry them on train tracks to the coin press room. There the hoppers dump the blanks onto a conveyor belt leading to the coin press. In 1943 mint workers thought they had made sure than no 1942 copper blanks remained in the hoppers. They missed some because 1943 copper cents were later found in circulation. None are known in new condition. Genuine 1943 copper cents are rare and hard to find, and they can be extremely valuable. In 2010, a 1943-S graded MS62BN sold for a world record price for any U. S. small cent of 1.7 million dollars!Beware of fakes! Since the 1943 copper cents are so rare they have been a popular target of counterfeiters and other scam artists. Favorite methods of faking the 1943 copper cent include:copper plating a 1943 steel cent.altering the date of a Lincoln cent of another year to make it look like the last digit is a “3” -1948 is a common choice.casting a coin from scratch -very crude and easy to tell, coins are struck not cast.creating a die from a genuine 1943 steel cent and striking a copper flan with it. If you think you have a 1943 copper cent, how can you tell if it is genuine? Steel cents weigh 2.7 grams, copper cents weigh 3.11 grams. Steel cents are attracted to a magnet, copper cents aren’t. Compare the digits on a 1943 steel cent with your coin. The shape of the digits should be the same and there should not be tooling marks where empty space would be on the”3″. If your cent passes ALL of the above tests then it is time to get the coin certified by one of the grading services such as NGC or PCGS.1943 Centavo De Cobre 1972 Double Die Cent You Might Also Like Do I have a 1986 silver penny? I found a 1984-D dime in copper


scriber definition

d Definition of scriber: a sharp-pointed tool for making marks and especially for marking off material (such as wood or metal) to be cut

scriber

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Illustration of scriber First Known Use of scribercirca 1836Learn More about scriber See words that rhyme with scriber Seen and Heard What made you want to look up scriber? Please tell us where you read or heard it (including the quote, if possible).show


what agency can i report a scammer concerning my computer

The Department of Justice (DOJ) helps you report computer, internet-related, or intellectual property crime to the proper agency based on the scope of the crime. How to Protect Yourself Here are some ways to keep your computer and personal information safe when going online:

Online Safety

Online Safety Be aware of these scams when you're online. What's on This Page Online Security and Safety Internet Fraud Phishing and Vishing Online Security and Safety The internet makes many everyday tasks faster and more convenient, like shopping and banking, but it's important to be safe and responsible online. Scammers use the internet to try to trick you into sending them money or your personal information. Report Cyber Crime If you believe you have been a victim of an internet-related crime, report it to these government authorities: The Internet Crime Complaint Center (IC3) refers internet-related criminal complaints to federal, state, local, or international law enforcement. Keep in mind, you will need to contact your credit card company directly to notify them if you are disputing unauthorized charges on your card or if you suspect that your credit card number has been compromised. The Federal Trade Commission (FTC) shares consumer complaints covering a wide range of categories, including online scams, with local, state, federal, and foreign law enforcement partners. It cannot resolve individual complaints but can give you information on the next steps to take. EConsumer.gov accepts complaints about online and related transactions with foreign companies.

Do Learn how to spot common scams and fraud - Find out the warning signs of internet fraud, phishing, and other online scams. Update your computer software - Download the latest versions of your operating system, web browsers, and apps. Talk to your kids about being safe and responsible online - If you are a parent, help protect your kids online by teaching them about the risks. Don’t Don’t share your passwords or sensitive information with anyone you don’t trust - Think about why someone needs it and if you can really trust the request. Laptop security is also important when using a portable computer in public to help prevent all your valuable information stored on it from falling into the hands of an identity thief. Don’t use the same passwords for multiple accounts - Try to make your passwords unpredictable and avoid using names, dates, or common words. Don’t give out personal information over unencrypted websites - When shopping or banking online, only use websites that use encryption to protect your information as it goes from your computer to their server. Back to Top Internet Fraud Scam artists defraud millions of people each year by using internet services or software with internet access to trick victims into sending money or giving out personal information. That’s why it’s important to take steps to protect yourself from and report internet fraud. Types of Internet Fraud Common examples of internet fraud include: Data breaches - When sensitive data (personal or financial information) is leaked from a secure location to an untrusted environment at a corporate or personal level Malware - This involves dangerous software that is designed to disable computers and computer systems. Phishing or spoofing - When a scammer uses fake email, text messages, or copycat websites to try to steal your identity or personal information, such as credit card numbers, bank account numbers, debit card PINs, and account passwords Internet auction fraud - This involves the misrepresentation of a product advertised for sale on an internet auction site, or non-delivery of merchandise. Credit card fraud - When scammers fraudulently obtain money or property through the unauthorized use of a credit or debit card or card number Report Internet Fraud If you believe you've been a victim of internet fraud or cyber crime, report it to the Internet Crime Complaint Center (IC3) or by using the FBI’s online tips form. Your complaint will be forwarded to federal, state, local, or international law enforcement. You will need to contact your credit card company directly to notify them if you are disputing unauthorized charges from scammers on your card or if you suspect your credit card number has been compromised. How to Protect Yourself Take these actions before browsing or shopping for products and services on the internet: Do Learn how to spot internet fraud - Find out the warning signs of common fraud schemes, including phishing or spoofing, data breaches, and malware. Know your buyer or seller - If you don't know who you're buying from or selling to online, do some research. Update your antivirus software and antispyware programs - Most types of antivirus software can be set up to make automatic updates. If your operating system does not offer free spyware protection (programs to prevent software from collecting information about you without your consent), you can find inexpensive software to download from the internet or at your local computer store. But be careful of ads on the internet offering downloadable spyware. You should only install programs from a trusted source. Don’t Don’t give out your personal information to anyone you don’t trust - Never provide it in response to an email, a pop-up, or a website you've linked to from an email or web page. Don’t keep your computer on all the time - Leaving your computer running all the time will make it more prone to spyware and other attacks from hackers and identity thieves. Back to Top Phishing and Vishing Scammers use a variety of methods to try to steal your personal and financial information. They often try to make you feel comfortable with giving up your sensitive information by spoofing trusted logos of legitimate companies in an email or by pretending to be a family member or friend on the phone. Phishing Phishing is when a scammer uses fake email, text messages, or copycat websites to try to steal your identity or personal information, such as credit card numbers, bank account numbers, debit card PINs, and account passwords. The scammer may state that your account has been compromised or that one of your accounts was charged incorrectly. A scammer will instruct you to click on a link in the email or reply with your bank account number to confirm your identity or verify your account. They will sometimes threaten to disable your account if you don't reply, but don't believe it. Legitimate companies never ask for your password or account number by email. Report Phishing Scams Forward phishing email messages to spam@uce.gov or file a complaint with the Federal Trade Commission (FTC). Include the full email header of the scam message in your report. Find out how to do this by searching online for the name of your email service and the words “full email header.”How to Protect Yourself Here are some ways to protect yourself from phishing scams: Do Reach out if you’re unsure - If you believe that a company needs personal information from you, call the number from their legitimate website or your address book. Do not call the number or use the links in the email. Tell the customer service representative about the request and ask if your account has been compromised. Turn on two-factor authentication - If your account supports it, you can set it up to require your password and an additional piece of information (code sent to your phone or a random number generated by an app) when you log in. This protects your account even when your password has been stolen. Don’t Don't click on any links or attachments in the email - Any links, attachments, or phone numbers that you click on may contain a virus that can harm your computer. Even if links in the email say the name of the company, don't trust them. They may redirect to a fake website. Vishing and Smishing Similar to phishing, vishing (voice and phishing) and smishing (SMS texting and phishing) scammers also seek to steal your personal information. However, these scams target your mobile or landline phone instead of your computer. You may be directed to call a phone number to verify an account or to reactivate a debit or credit card. Report Vishing and Smishing Scams If you have received one of these requests, report it to the Internet Crime Complaint Center (IC3). Your complaint will be forwarded to federal, state, local, or international law enforcement. You will need to contact your credit card company directly to notify them if you are disputing unauthorized charges on your card from scammers, or if you suspect your credit card number has been compromised. Victims of these scams could also become victims of identity (ID) theft. Visit Identity Theft.gov to learn how to minimize your risk. Share This Page: Back to Top Do you need help? Ask us any question about the U. S. government for free. We'll get you the answer or tell you where to find it. Call USA.gov Chat with USA.gov Email USA.gov What you think matters!Was this page helpful? Yes No Next Form Approved OMB#3090-0297 Exp. Date 07/31/2019Last Updated: March 05, 2018


can blueberries make your stool black

ry Back to Top Considerations Heavy or rapid bleeding in the upper GI tract can cause bright red stools. Eating black licorice, lead, iron pills, bismuth medicines like Pepto-Bismol, or blueberries can also cause black stools. Beets and tomatoes can sometimes make stools appear reddish. In these cases, your doctor can test the stool with a chemical to rule out the presence of blood.

Bloody or Tarry Stools

"Search Health 3,000+ Topics Send Feedback Health > Times Health Guide > b > Bloody or Tarry Stools Bloody or Tarry Stools Overview Alternative Names Considerations Causes References Related Topics Diverticulitis Vomiting Blood Illustrations Lower Digestive Anatomy Bloody stools often are a sign or a problem in the digestive tract. Blood in the stool may come from anywhere along your digestive tract from your mouth to your anus. Reference from A. D. A. M. Back to Top Alternative Names Stools - bloody; Hematochezia; Melena; Stools - black or tar

Bleeding in the esophagus or stomach (such as with peptic ulcer disease) can also cause you to vomit blood. Back to Top Causes Bleeding that takes place in the esophagus, stomach, or the first part of the small intestine most often causes the stool to appear black or tarry. Your doctor may use the term ""melena. ""Bleeding in the upper part of the GI tract will usually cause black stools due to: Abnormal blood vessels A tear in the esophagus from violent vomiting (Mallory-Weiss tear)Bleeding ulcer in the stomach When blood supply is cut off to part of the intestines Inflammation of the stomach lining ( gastritis)Trauma or foreign body Widened, overgrown veins (called varices) in the esophagus and stomach Maroon-colored stools or bright red blood often men that the blood is coming from the small or large bowel, rectum, or anus. The term ""hematochezia"" is used to describe this finding. Abnormal blood vessels Anal fissures When blood supply is cut off to part of the intestines, called bowel ischemia Polyps or cancer in the colon or small intestine Diverticulosis (abnormal pouches in the colon)Hemorrhoids (common cause of bright red blood)Inflammatory bowel disease (such as Crohn's disease or ulcerative colitis)Infection in the intestines Trauma or foreign body Back to Top References Jensen DM. Gastrointestinal hemorrhage and occult gastrointestinal bleeding. In: Goldman L, Schfer AI, eds Cecil Medicine. 24th ed. Philadelphia, Pa: Saunders Elsevier; 2001:chap137Laine L, Jensen DM, American College of Gastroenterology guideline for management of patiant with ulcer bleeding. Am J Gastroenterol. 2012; 107;345-360Lanza FL, Chan FK, Quigley EM; Practice Parameters Committee of the American College of Gastroenterology. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol. 2009; 104;728-738Lieberman DA. Clinical practice. Screening for colorectal cancer. N Engl J Med . 2009;361:1179-1187. More Information on This Topic Review Date: 1/6/2013 Reviewed By: David C. Dugdale, III, MD, Professor of Medicine, Division of General Medicine, Department of Medicine, University of Washington School of Medicine. Also reviewed by A. D. A. M. Health Solutions, Ebix, Inc., Editorial Team: David Zieve, MD, MHA, Bethanne Black, Stephanie Slon, and Nissi Wang. A. D. A. M., Inc. is accredited by URAC, also known as the American Accreditation Health Care Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A. D. A. M. follows rigorous standards of quality and accountability. A. D. A. M. is among the first to achieve this important distinction for online health information and services. Learn more about A. D. A. M.'s editorial policy, editorial process and privacy policy. A. D. A. M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch). A. D. A. M. Copyright The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997- 2008 A. D. A. M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited. "


mexico population policy life expectancy

World Rank76.7 46According to the latest WHO data published in 2015 life expectancy in Mexico is: Male 73.9, female 79.5 and total life expectancy is 76.7 which gives Mexico a World Life Expectancy ranking of 46. You can see the top 20 causes of death data and rankings for Mexico by clicking on the links below or select the full country health profile at the bottom of the page. Top 20 Causes of Death Mexico Click each link to see data

Mexico : Life Expectancy

SELECT COUNTRYAfghanistan Albania Algeria Angola Arab Emirates Argentina Armenia Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bhutan Bolivia Bosnia/Herzeg. Botswana Brazil Brunei Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Central Africa Chad Chile China Colombia Comoros Congo Costa Rica Cote d Ivoire Croatia Cuba Cyprus Czech Republic Denmark Djibouti Dominican Rep. DR Congo Ecuador Egypt El Salvador Equ. Guinea Eritrea Estonia Ethiopia Fiji Finland France Gabon Gambia Georgia Germany Ghana Greece Guatemala Guinea Guinea-Bissau Guyana Haiti Honduras Hungary Iceland India Indonesia Iran Iraq Ireland Israel Italy Jamaica Japan Jordan Kazakhstan Kenya Kuwait Kyrgyzstan Laos Latvia Lebanon Lesotho Liberia Libya Lithuania Luxembourg Macedonia Madagascar Malawi Malaysia Maldives Mali Malta Mauritania Mauritius Mexico Moldova Mongolia Montenegro Morocco Mozambique Myanmar Namibia Nepal Netherlands New Guinea New Zealand Nicaragua Niger Nigeria North Korea Norway Oman Pakistan Panama Paraguay Peru Philippines Poland Portugal Qatar Romania Russia Rwanda Saudi Arabia Senegal Serbia Sierra Leone Singapore Slovakia Slovenia Solomon Isl. Somalia South Africa South Korea South Sudan Spain Sri Lanka Sudan Suriname Swaziland Sweden Switzerland Syria Tajikistan Tanzania Thailand Timor-Leste Togo Trinidad/Tob. Tunisia Turkey Turkmenistan Uganda Ukraine United Kingdom United States Uruguay Uzbekistan Venezuela Viet Nam Yemen Zambia Zimbabwe SELECT COUNTRYAfghanistan Albania Algeria Angola Arab Emirates Argentina Armenia Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bhutan Bolivia Bosnia/Herzeg. Botswana Brazil Brunei Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Central Africa Chad Chile China Colombia Comoros Congo Costa Rica Cote d Ivoire Croatia Cuba Cyprus Czech Republic Denmark Djibouti Dominican Rep. DR Congo Ecuador Egypt El Salvador Equ. Guinea Eritrea Estonia Ethiopia Fiji Finland France Gabon Gambia Georgia Germany Ghana Greece Guatemala Guinea Guinea-Bissau Guyana Haiti Honduras Hungary Iceland India Indonesia Iran Iraq Ireland Israel Italy Jamaica Japan Jordan Kazakhstan Kenya Kuwait Kyrgyzstan Laos Latvia Lebanon Lesotho Liberia Libya Lithuania Luxembourg Macedonia Madagascar Malawi Malaysia Maldives Mali Malta Mauritania Mauritius Mexico Moldova Mongolia Montenegro Morocco Mozambique Myanmar Namibia Nepal Netherlands New Guinea New Zealand Nicaragua Niger Nigeria North Korea Norway Oman Pakistan Panama Paraguay Peru Philippines Poland Portugal Qatar Romania Russia Rwanda Saudi Arabia Senegal Serbia Sierra Leone Singapore Slovakia Slovenia Solomon Isl. Somalia South Africa South Korea South Sudan Spain Sri Lanka Sudan Suriname Swaziland Sweden Switzerland Syria Tajikistan Tanzania Thailand Timor-Leste Togo Trinidad/Tob. Tunisia Turkey Turkmenistan Uganda Ukraine United Kingdom United States Uruguay Uzbekistan Venezuela Viet Nam Yemen Zambia Zimbabwe Mexico : Life Expectancy Male Female73.9 79.5Total

Life Expectancy1. Diabetes Mellitus2. Coronary Heart Disease3. Stroke4. Violence5. Lung Disease6. Liver Disease7. Hypertension8. Influenza and Pneumonia9. Prostate Cancer10. Kidney Disease11. Other Injuries12. Road Traffic Accidents13. Breast Cancer14. Endocrine Disorders15. Congenital Anomalies16. Malnutrition17. Cervical Cancer18. Lung Cancers19. Stomach Cancer20. Liver Cancer See full health profile and world rankings for Mexico here: Mexico Health Profile Data Source: WHO 2015


how long does it take for sun to rotate

The Sun does rotate, but not all at the same rate. While the Earth takes 24 hours to do one rotation, whether you are standing at the equator or close to either the South or North Pole, the Sun actually rotates fastest at its equator. On the Sun’s equator any point takes 24.47 days to rotate completely around the star but as you get close to either of the Sun’s poles it can take up to 38 days. These measurements have been made by using sunspots as tracers of the surface and watching them turn with the star.

Does the Sun rotate?

Does the Sun rotate?by Jonathan O'Callaghan, 4 December 2012Is the heart of our Solar System spinning like the planets do?0comments

Astronomers usually work with the rotation rate of an area about 26 degrees above or below the equator as this is where the most sunspots are observed. At this latitude, one complete rotation takes just over 27 days and this is known as a Carrington rotation. Answered by Megan Whewell from the National Space Centre Tags: solar system revolution, spinning star, Sun rotation speed


sandra bullock is she republican or democrat

Sandra Bullock to play filibustering Democrat Wendy Davis in forthcoming biopic Let Her Speak. Sandra Bullock, 53, has been attached to play Democratic politician Wendy Davis in Let Her Speak.

Sandra Bullock to play filibustering Democrat Wendy Davis in forthcoming biopic Let Her Speak NEW TOP SHOWBIZSubscribe Add to Share More39 views10Published on Nov 11, 2017

The Academy Award winner agreed to play the 54-year-old Texas State Senator in a film focusing on the 13 hour filibuster Davis performed in order to thwart a GOP anti-abortion law in 2013. Subscribe my channel for More Interesting videos every Day. https://goo.gl/9K7yn YShow more Loading...


how old can a baby get its first hair

As long as you plan this event for just the right time, it should go pretty well. Babies with a full head of hair usually need their first haircut at around 8 or 9 months of age. There have been some baby’s hair that need one as early as 6 months or some as late as 2 years old. It just depends on the baby and when you are ready. One thing to think about as a parent is if you wish your baby to look like a baby or if you are ready to make them look a little more grown-up.

Baby Haircut

Baby Haircut One of the biggest milestones for your new baby is getting the first baby haircut. Your baby’s newborn hair is one of the most special parts of being a baby. The sweet little curls and soft hair is a joy for mommies and daddies to stroke and cuddle. There comes a time when your baby will need his or her first haircut and you may want to know the best place or how to trim your baby’s hair. The choice of where you get your baby’s first haircut is entirely up to you. Hair salons can be costly, so you may want to try and do the first haircut yourself at home. Wherever you choose, just make sure you keep a special lock of your baby’s hair. This is a very special event and you will want to remember those first curls. When Is a Good Time for Getting the First Baby Haircut? Even though getting the first baby haircut is very special for you, your baby may not think so. It can be a frightening experience the first time and you may have a fussy, wiggly child on your hands. Think about it: They make you sit still in a chair, place a drape around your shoulders, they spray you with water and come at you with scissors. All of this is done by a complete stranger. If your child suffers from “stranger anxiety” which happens around 9 months, you may end up with a screaming child who is now afraid of haircuts.

Just know that baby curls usually do not return after the first haircut and hair will begin to grow in thicker after a trim. How to Give Babies Their First Haircut at Home Giving your baby the first haircut yourself at home may alleviate anxiety and make the experience easier for your baby. If you feel comfortable doing this yourself, here are some instructions on how to cut your baby’s hair:1. Pick a Good Time for You and Your Baby Finding the best time that your baby will not be fussy or wiggly will help. Make sure your baby isn’t tired or hungry before the haircut. The best time is usually after a meal and prior to a nap.2. Place Your Baby in a Good Safe Place You can use a highchair, booster seat with straps or anything that helps your baby sit up straight, but not crawl away from you. The most important part is that your baby is able to sit upright and hold his or her head up on their own. That is why 8 or 9 months is a good time. Allow your baby to read a book or play with a toy.3. Figure out How Long You Want Your Baby’s Hair to Be New baby hair tends to grow uneven the first year. It may be thinner or thicker in some spots or different lengths. If you try to over-correct for these issues, you may end up with hair that is too short. Maybe just a slight trim the first time is enough.4. Use Sharp Scissors Borrow or invest in a good pair of hair scissors. Scissors that you use around the house everyday may be too dull and can pull your baby’s hair. Besides, good sharp scissors will cut faster and the experience will be over quicker than if you are struggling to cut the hair.5. Only Cut Small Sections at a Time This prevents errors and uneven cutting. Use clips to hold other hair to the side while you work on just one small section. Squeeze the section you’re working on between your thumb and forefinger and only cut about a quarter of an inch at a time. After you are done, you can always trim some more if needed.6. Don’t Push the Issue If your baby gets fussy or wiggly, stop the haircut and try again after your baby has calmed down. Maybe try a snack and/or a nap and then try later. Watch this helpful video on how to give a baby haircut: More Tips on Getting the First Baby Haircut at a Salon Tips Description Only trim your baby’s hair The first haircut only needs to be a little trim off the edges. This will help baby get used to the experience. Save the major haircuts after baby has been once or twice. Tell your hairstylist exactly what you are thinking or baby’s hair might end up too short. Choose a reliable hairstylist It is always a good idea to use a hairdresser that you know already. If so, both you and baby will have a relaxed happy experience. If you don’t personally know a stylist, find one from friend’s referrals that they know and trust. Bring some distractions Your baby will not understand why a complete stranger is coming at them with scissors and may fuss. Try bringing snacks, a favorite toy or a few books to distract them. Pick the right time Early in the day after breakfast and before naptime is the best time of day for a first haircut. Afternoons or right around naptime may mean a fussy baby. Play pretend hairdresser at home Show your baby how haircuts are by pretending at home. Start by putting baby in a chair in front of a mirror, wrap something around his or her shoulders and pretend to cut their hair. This will help them understand what is going on at the salon. Keep a small lock of hair Some salons have “first haircut” certificates that you can tape hair onto. Make sure you ask when you go. If not, ask to keep a small lock of hair that you can place in a baby book at home. Don’t worry if it’s not good Stay calm if baby’s first cut doesn’t look like you wanted. A squirmy baby can cause some unevenness and it may just look funny because it isn’t what you are used to. The good news is it will grow back and you can try different styles with each cut. What Are the Different Traditions for Baby’s First Haircut? Tradition Meaning An initiation Newborn Muslim babies have their head shaved as a cleansing and initiation into the faith. Traditionally, the hair used to be weighed and a donation given in silver matching the weight of the hair. Nowadays, just a charitable donation is made in the baby’s honor. The new hair is either washed away in a body of water or sometimes just tossed out. As an offering Hindu babies will have their head shaved at around 7 months old to offer up to the family deity. The hair shaving ritual either takes place in the family temple or can be done at a hair salon and people place the hair in the temple at a later date. This ritual takes place at any of the odd numbered months in the first year. A symbol of good luck Chinese tradition says that the first haircut in a baby’s life is a symbol of good luck. There is a one-month recovery period and then the grandmother of the baby performs the first haircut. She then places a red hat on the baby. Some hair is left on the head. Chinese people are saddened that this tradition is done less and less in modern times. Beginning of education In the Jewish faith, boys do not get their hair cut until they are 3 years old. This haircut signals the beginning of their education and celebrating their 3 rd birthday. This tradition is called an “upsherenish”. End of babyhood In any tradition or culture, the first haircut and taking off those soft baby curls means an end to “babyhood” and a more mature grown-up hairstyle. This is thought of a significant milestone in a baby’s life and a rite of passage into being a young child.


dcu electronic routing number

Routing Number DCU's Routing Number: 211391825An ABA number sometimes known as a check routing number or routing transit number (RTN), is a sequence of nine numeric characters used by financial institutions, including credit unions and banks to identify specific financial institutions within the United States.

Routing Number

An ABA number is used for wires and electronic automatic clearing house (ACH) transactions such as electronic funds transfer, direct deposit, direct payment of consumer bills, e-checks, and tax payments, among others. DCU's ABA Routing Number is: 211391825


how long is the bachelor finale

The finale is two hours long, and it's followed by an hour-long live after show (that promises a ""first"" in Bachelor history) immediately after at 10 p.m. EST on ABC.

What Time Is 'The Bachelor' Season Finale on Tonight? Plus Everything You Need to Know About Nick Viall's Final Rose!

"Updated: Mar 13, 2017 11:48 am By Emma Hernandez Getty Images It's finally here! The season finale of The Bachelor is set to air tonight — and Nick Viall will hand out his final rose and end up (hopefully!) engaged by the end of the of the night! Here's everything you need tonight about the final episode. MORE: Chris Soules Breaks Silence on ""Difficult"" Breakup With Whitney Bischoff What time is The Bachelor on tonight? The finale starts at 8 p.m. EST on ABC. How long is The Bachelorfinale?

MORE: 'Bachelor' Villain Corinne Olympios Plans to Expose What Nick Viall Is Like in Bed!Who is left on the show? Nick has to choose between Vanessa Grimaldi and Raven Gates. Who does Nick pick on The Bachelor? In an effort to not spoil the show for those who want to wait, you can click here to find out who wins. An unanticipated problem was encountered, check back soon and try again Error Code: MEDIA_ERR_UNKNOWNSession ID: 2018-04-12:596f772fc1cfd72de39e16bb Player ID: vjs_video_3OKMORE: What Does Nick From 'The Bachelor' Do? — Get the Details!But what we do know is that choosing his leading lady was a difficult decision and Nick was completely stressed out while filming his scenes for the season finale. Sources exclusively revealed to Life & Style that he even wrote down a list of pros and cons for Raven and Vanessa before he popped the question.“Nick told producers he felt like he was in hell,” said the insider. “He was having a complete breakdown and needed reassurance on who he was picking.”The 36-year-old even sought out advice from host Chris Harrison before he made his final decision.“Nick was having mixed emotions,” the insider said of the finale, which was filmed in Finland during frigid temperatures. “He’s in love with both [women].”Share Tweet Pin it "


what is levofloxacin and what is it used for

Levaquin is the brand name for levofloxacin, a prescription antibiotic drug used to treat a variety of bacterial infections, such as: Pneumonia Acute bacterial sinusitis

What Is Levaquin (Levofloxacin)?

"What Is Levaquin (Levofloxacin)?57 Reviews

Chronic bronchitis worsened by bacterial infections Skin infections Chronic prostate gland infection (prostatitis)Urinary tract infection (UTI)Acute kidney infection Inhalational anthrax, or anthrax contracted by breathing in anthrax spores Pneumonic and septicemic plague (Levaquin is also used to prevent contracting plague)Levaquin belongs to a class of antibacterial agents called fluoroquinolones, which kill bacteria by inhibiting the activity of certain enzymes bacteria require to replicate, transcribe, repair, and recombine DNA. Doctors may also prescribe Levaquin ""off-label"" to treat or prevent other bacterial infections, including tuberculosis (TB), Salmonella food poisoning, Shigella food poisoning, Campylobacter infections, and disseminated Mycobacterium avium complex disease, especially for people with a weakened immune system from HIV or other conditions. Levaquin was first approved by the Food and Drug Administration (FDA) in 1996, and is produced by Janssen Pharmaceuticals, Inc, a subsidiary of Johnson & Johnson. Levaquin and Tendon Issues In 2008, the FDA required all fluoroquinolone manufacturers to include a black-box warning that the drug class can increase a person's risk of tendonitis (tendon inflammation) and tendon rupture, a decision that came too late for a lot of people taking Levaquin, resulting in numerous lawsuits. Plaintiffs charge that Johnson & Johnson should have strengthened their warnings about the potential tendon issues associated with Levaquin before the FDA issued its decree, and also that the company downplayed the drug's risks to boost sales. In 2010, Johnson & Johnson lost a court case against 87-year-old John Schedin, and had to pay nearly $2 million to Schedin for the damage he received to his Achilles tendon after taking Levaquin. The company subsequently won several other court cases, in which plaintiffs failed to show the drug caused their tendon issues. To date, however, thousands more cases have reached settlements out of court. The risk of tendonitis and tendon ruptures is greater for people over 60 years old, people taking corticosteroid drugs, and people with kidney, heart, or lung transplants. Physical activity or exercise, kidney failure, and having previous tendon problems, such as rheumatoid arthritis, can also increase your risk of tendon issues while taking Levaquin. Levaquin Warnings You should not take Levaquin if you have a known sensitivity or allergy to levofloxacin and other quinolones (the family of antibiotics that encompasses fluoroquinolones). You should also avoid the drug if you have the neuromuscular disease myasthenia gravis, as the drug could worsen your muscle weakness. Some people experience other serious and sometimes life-threatening reactions from taking Levaquin, such as: Dangerous skin disorders, including toxic epidermal necrolysis and Stevens- Johnson Syndrome Blood vessel inflammation, joint pain, and muscle pain Allergic pneumonitis, an inflammation of the walls of the lung's air sacs Interstitial nephritis (a kidney disorder) and kidney failure Hepatitis (liver inflammation), jaundice (yellowing of the skin and eyes), liver cell death, and liver failure Blood-related issues, including deficiencies in red blood cells or white blood cells Pregnancy and Levaquin It's unknown if Levaquin can harm a developing fetus because no adequate and well-controlled studies have been carried out in pregnant women. However, the drug's antimicrobial benefits to the mother may outweigh the potential risks to her unborn child. Levofloxacin is presumed to be present in breast milk, and the drug has the potential to cause serious side effects in infants. Breastfeeding mothers taking Levaquin should either discontinue the drug or stop breastfeeding. Back to Top Levaquin Side Effects Common Side Effects of Levaquin The most common side effects of Levaquin are: Nausea Headache Diarrhea Insomnia Constipation Dizziness Other common side effects include yeast infections, vaginitis, severe itching, chest pain, and swelling from water buildup (edema). Severe Side Effects of Levaquin Though rare, Levaquin can result in numerous serious side effects that may require medical attention, including: Central nervous system effects, including seizers, hallucinations, nightmares, depression, confusion, paranoia, suicidal thoughts, and tremors Gastrointestinal infections and disorders Potentially irreversible peripheral neuropathy (damage to the nerves outside the brain and spinal cord)Serious heart rhythm changes Joint problems Changes in blood sugar Sensitivity to sunlight Severe diarrhea from the difficult-to-treat bacteria Clostridium difficile Additionally, children taking Levaquin may develop musculoskeletal disorders, such as arthritis and gait abnormalities. Back to Top Levaquin Interactions Levaquin may interact with: Antacids, multivitamins, and supplements containing magnesium, aluminum, iron, or zinc Sucralfate (Carafate)Didanosine (Videx)Warfarin (Coumadin, Jantoven)Antidiabetic medicine Non-steroidal anti-inflammatory drugs, including aspirin and ibuprofen Theophylline (Theo-24, Theolair)Make sure to tell your doctor about any medications, drugs, and supplements you take, especially steroid medications, anti-psychotic drugs, tricyclic antidepressants, diuretics, and heart-rate medications. Levaquin and Other Interactions Levaquin may produce a false-positive urine test for opiates. You should tell your doctor or other healthcare professional that you’re taking Levaquin when submitting a urine sample. Back to Top Levaquin Dosage Levaquin comes in the various forms: Film coated oral tablets of 250 milligrams (mg), 500 mg, and 750 mg Oral solutions of 25 mg per milliliter (m L), which should be taken 1 hour before or 2 hours after eating Premixed, single-use injection in flexible containers, containing a solution equivalent to 250 mg, 500 mg, or 750 mg of levofloxacin Single-use injection vials containing concentrated levofloxacin solution equivalent to 500 mg or 750 mg, which need to be further diluted with the appropriate solution Only take Levaquin as advised by your doctor. Dosage and length of treatment differs depending on the type of infection that needs to be treated; adults with kidney problems, as well as children, must follow an adjusted treatment schedule. Levaquin Overdose According to animal studies, Levaquin is toxic in high doses, causing a number of muscular and nervous system symptoms, such as tremors, convulsions, and loss of control of bodily movements. Call your local poison control center or visit the nearest emergency hospital room if you've overdosed on Levaquin to have your stomach emptied. Call 9-1-1 if you think someone has overdosed and has collapsed or isn't breathing. Missed Dose of Levaquin Take the missed dose as soon as you remember it, unless it's almost time for next dose. Never double your dose to make up for a missed dose of Levaquin. Back to Top "


what was stalin scorched earth policy

True or not, this amount of time lapsed before Stalin addressed the Russian people about the nature of the calamity that was upon them. In a halting, somber tone, Stalin spoke to the Russian people in a radio broadcast on July 3, 1941, imploring them not to give up hope. He reminded them of Napoleon, and the defeat of his armies. Hitler was no more invincible than the French Emperor, he declared. Stalin called for a ""Scorched Earth"" behind the retreat of the Russian armies, non-cooperation, and partisan warfare on the part of the occupied territories. He also expressed gratitude for the promises of support from the Western democracies.

"Military History Online.com Home Genealogy Forums Search Contact MHO Home MHO Home Ancient Medieval17th Century18th Century19th Century American Civil War World War IWorld War IIKorea Vietnam20th - 21st Century Write for MHOSearch MHOCivil War Genealogy Database Privacy Policy WWII Sections MHO Home WWII Home Battle of Stalingrad Sections WWII Home Stalingrad Home Operation Barbarossa <<<Operation Blue The Commanders Death of a City Rattenkrieg Uranus and Saturn Der Kessel Annihilation and Aftermath Mike Yoder Articles Battle of Stalingrad Ray A. Yoder WWII Photos Ads by Google Battle of Stalingrad Operation Barbarossa by Mike Yoder On June 22, 1941, the German Army poured across the borders of the Soviet Union, initiating nearly 4 years of the most savage and brutal warfare humanity ever experienced. Three Army Groups penetrated Russia on a front extending from the Baltic coast to the Black Sea. One and a half million soldiers of the Wehrmacht obeyed the Fuehrer's directive to destroy the Red Army and the Soviet Union. ""The World will hold it's breath! "", Adolf Hitler told his Generals. And as the world watched in amazement, the Wehrmacht rolled triumphantly across the Russian steppe, seemingly invincible. Caught by surprise, the bulk of the Russian Air Forces were destroyed on the ground. Under orders not to provoke the Germans, the Russian frontier armies were not given coherent directions to mount a defense of their borders. The Red Army fell back in disorder, surrendered in wholesale numbers, or died in a futile effort to halt the German advance. Western military experts gave the Russians 6 weeks, perhaps 8 at the most, before suffering total military disaster at the hands of the Germans. Battered by one defeat after another, the poor performance of the Red Army gave no one reason to believe otherwise. With their officer corps decimated by Stalin's purges, the badly equipped , poorly trained and demoralized Red Army sustained losses and gave ground which would have defeated any other country in a matter of days. For the invasion, Hitler chose the same armies and commanders which had swept through the Low Countries and France in a little over a month. Army Group North, commanded by Generalfeldmarshall Wilhelm Ritter von Leeb, launched their attack from East Prussia, driving for the Baltic port of Leningrad. Army Group Center, under Gfm. Fedor von Bock, erupted out of Poland, with Moscow as it's objective. Under the command of one of Germany's ""Black Knights"", Field Marshal Gerd von Rundstedt, Army Group South headed for the Ukraine, and the oil fields of the Caucasus. Facing them in the field were their Soviet counterparts, Soviet Marshals Klimenti Voroshilov, an old Bolshevik, drinking partner, and crony of Stalin; Semyon Buddeny, a cavalry officer of indifferent ability in modern warfare, and Semyon Timoshenko, one of the few capable high ranking officers to survive Stalin's purges. Anticipating the easy capture of Moscow, Leningrad, and the Caucasus, the planners of Oberkommando der Wehrmacht (High Command of the Armed Forces, or OKW) gave themselves less than 6 months to effectively destroy the Red Army, occupy European Russia, and halt Operation Barbarossa at the foothills of the Ural Mountains. In Hitler's view, this would secure for Germany all the living space, food, and mineral resources it would ever need, and would in effect constitute victory for the Reich in the Second World War. German surprise and success was so overwhelming in the first few weeks that few would have disagreed with that assessment. On top of the disasters suffered by the Red Army, the Soviet government itself seemed to fall into disarray. Joseph Stalin is reported to have gone nearly catatonic for 11 days, while Soviet Foreign Minister Vyacheslav Molotov effectively ran the government.

Western support was immediately forthcoming from Great Britain. After standing alone against the Nazis for an entire year, Winston Churchill stated that, ""All who resist Nazi domination shall have our aid"". Derided by opposition members of Parliament about his long-standing position against Communism, Churchill retorted, ""If Hitler were to invade Hell, I should at least stand in the Commons and say a few words on behalf of the Devil"". Rhetoric aside, there was little that Britain could offer of immediate assistance, and Russia faced the German onslaught alone. One disaster after another plagued the Red Army as the Germans drove deeper into the Russian heartland. By July 16, 1941, Army Group Center had captured over 600,000 prisoners alone. An ill-conceived and executed counter-attack at Kharkov cost the Red Army over 300,000 men. The Wehrmacht had captured the city of Smolensk, and the road to Moscow appeared to be open. In the north, Field Marshal von Leeb's forces had approached the outskirts of Leningrad. Here the Germans shied away from an all-out street fight to take the city. The Finns, in the meantime, had resumed war with the Soviet Union, and their forces combined with the Germans, surrounded Leningrad for a 900 day long siege. Leningrad held, at the cost of one and a half million civilians dead, from starvation, disease, and exposure. However, the Germans were not without problems of their own. For reasons best understood by Hitler, they diverted vital resources to enhance the push upon Kiev, and the drive towards Moscow faltered. By the time Kiev was in German hands and the prime objective shifted back to Moscow, time and the Russian winter was starting to work against them. Stalin had recognized the vital work of Gen. Georgi Zhukov at Leningrad, and directed him to marshal the resources necessary to save the Soviet capital from being over-run. From Oct. 1941, Field Marshal von Bock had concentrated his armor and infantry to close upon Moscow, spear-headed by the master of the Panzers, Gen. Heinz Guderian. In the closing days of October, 1941, Stalin held the annual observance of the Bolshevik Revolution in Red Square. The military review was held as usual, but the soldiers continued marching out of the city, directly towards the front. The Red Army fought a delaying operation at the approaches to the city, while Zhukov gathered forces for a counter-attack. On or around Dec. 8, 1941, an advance patrol from Panzer Gruppe Guderian was within eyesight of the spires of the Kremlin. This was probably the closest the Germans ever came to their dream of conquering Soviet Russia. Army Group Center, exhausted and over-extended, had been pushed to the limit. With an impeccable sense of timing, Zhukov struck back. Fresh reserves of infantry, armor, and cavalry fell upon the German front lines. German troops, still wearing summer uniforms and ill-prepared for the Russian winter, fought back as best they could, but were overwhelmed. Von Bock's soldiers bled and died in the snow, and the front of Army Group Center crumbled. OKW insisted upon an immediate withdrawal, and an end to the Russian adventure. Hitler overruled his Generals, giving a firm order to stand fast and fight to the last man. The Luftwaffe jury-rigged airlifts of supplies to relieve isolated pockets. The experience and training of German staff officers improvised strategies to hold off the Soviets while they rallied their shattered armies and held their ground. The inexperience of the Soviets at a war of rapid movement made it impossible for them to press their advantage and finish off their opponent. All these factors combined enabled the Wehrmacht to hold their position in Russia, and to embellish the myth of Hitler as a military genius. One year later, this same military genius would lead the German 6th Army into a mass grave at Stalingrad. * * *< Previous Page Next Page >* * *Copyright © 2003 Mike Yoder. Written by Mike Yoder. If you have questions or comments on this article, please contact Mike Yoder at: mikeyzinaz@hotmail.com . About the author: Coming soon... Published online: 02/04/2003. * Views expressed by contributors are their own and do not necessarily represent those of MHO.© 2016 Military History Online.com, LLC Contact Brian Williams at: militaryhistoryonline@hotmail.com "

1 Scorched earth policy is a strategy of warfare whereby the retreating armed forces destroy or devastate whole towns, facilities, agriculture, transport routes, and general infrastructure in order to deprive the advancing enemy forces or the belligerent population of food, shelter, fuel, communications, and other valuable resources that may be useful for them.

Scorched Earth Policy

Max Planck Encyclopedia of Public International Law [MPEPIL]Scorched Earth Policy Alexander Schwarz, Maria Grigat Content type: Encyclopedia entries Article last updated: September 2015Product: Max Planck Encyclopedia of Public International Law [MPEPIL]Subject (s): Cultural property / heritage — Conduct of hostilities Published under the auspices of the Max Planck Foundation for International Peace and the Rule of Law under the direction of Rüdiger Wolfrum.

Scorched earth strategies regularly have a negative impact on the civilian population left behind ( Civilian Population in Armed Conflict ). Although not specifically defined under international law, the... Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.


what is the survival rate for untreated melanoma

Being such a late stage melanoma, the metastatic stage has a 10-year survival rate of less than 10% (NIH 2009), with a life expectancy of 2-7 months, depending on the number of organs the cancer has spread to (Treatment Trials 2010).

What is Metastatic Melanoma?

What is Metastatic Melanoma?04 October 2012, By oncosec , 0 Comments As the largest organ of the body, the skin protects us from a myriad of conditions, parasites, and other foreign agents. Be that as it may, it is also highly susceptible to different diseases, viruses, and cancers. Different skin types can be more resistant or more susceptible to different conditions. One type of cancer that aggressively attacks the skin is melanoma: the later stage of which is known as metastatic melanoma. Often referred to as the most hazardous form of skin cancer, melanoma tends to start as spots or moles on the skin. As a fast spreading cancer, this can quickly move into the surrounding skin and organs. Described as a cancer of the melanocytes (the cells which produce melanin: a pigment responsible for color in the skin), melanoma can actually start in many areas of the body. However, it is predominantly found in the skin. While it is less common than other types of skin cancer, melanoma is notorious for having low life expectancies – especially if not treated until the later stages – and becomes progressively more difficult to treat, as the cancer advances. The incidence for melanoma is expected to be 76,250 in 2012 according to the National Cancer Institute. Metastatic melanoma is Stage III and IV of the cancer. This stage involves the spread of melanoma into the lymph nodes and other areas of the body such as the brain, lungs, liver and other organs.

Many different types of melanoma are referred to as metastatic, once they have spread to a second site in the body. This includes cutaneous, mucosal and ocular varieties. Unlike some other aggressive cancers, as it spreads, the cells remain melanoma cells, instead of becoming another type of cancer. Figure depicts metastatic melanoma that has spread into the lymph nodes There are many risk factors that increase the chance of developing melanoma. These factors include sensitivity and overexposure to the sun, fair complexions (especially those with fair skin, blonde or red hair, and blue eyes), individuals who have had severe sunburns as a child, those with a family history of skin cancers, and having a large number of moles (especially if they are of an irregular shape). It is highly advisable to have any strange moles or pigmentations of the skin checked by a physician, as soon as possible. When expecting to spend large amounts of time in the sun, always prepare yourself with sunscreen or sunblock and avoid extended periods in direct sunlight, during peak hours. The prognosis of metastatic melanoma is extremely dependent on how far the cancer has spread. Because of how advanced Stage IV tends to be, prognoses are generally poor. Patients who are diagnosed and begin treatment before the cancer has spread to other organs have a much higher chance of successful treatment and survival. Metastatic melanoma has historically been difficult to treat, because of its aggressive, quick moving nature. In the past, some successful methods for fighting this type of cancer were found to create levels of toxicity in the body at too high an amount to be feasible as legitimate methods of treatment. However, Onco Sec is currently involved in bringing new methods of treatment to the forefront of fighting metastatic melanoma. Initial trials showed that Onco Sec’s Immuno Pulse therapy is safe and can achieve effective results without the harsh side effects of traditional treatments like radiation and chemotherapy. This method of gene therapy utilizes a plasmid DNA construct that instructs the body to produce IL-12 protein: integral to stimulating the immune system to recognize and destroy cancer cells. With a minimal dosage, this therapy has been found to be effective at killing melanoma cells, while being safer and less toxic then traditional therapies. In a Phase I study, 90% of treated lesions responded to Immuno Pulse therapy while 53% of patients with metastatic disease showed regression of at least some of their metastatic disease. Even more encouraging was that, 16% of patients showed complete regression of the cancer after only one treatment of Immuno Pulse. Onco Sec is currently enrolling participants for a Phase II trial using Immuno Pulse for Stage III-IV metastatic melanoma. Approximately 25 patients will be enrolled into this trial. It is believed that this treatment could be a safer and more effective alternative than current therapies for late-stage metastatic melanoma. If you or a loved one has been diagnosed with this devastating disease, and you would like to learn about Onco Sec’s Immuno Pulse therapy, please see more information on the clinical trial. If you would like to learn more about metastatic melanoma or Onco Sec, please consult our website. You can also contact us on Facebook and Twitter.


how does programmatic buying work

Its a change from traditional ad buying. No longer a buyer agrees to run a certain number of ads with a publisher and is locked in to the contract. Programmatic media buying, marketing and advertising is the algorithmic purchase and sale of advertising space in real time. During this process, software is used to automate the buying, placement, and optimisation of media inventory via a bidding system.

What is Programmatic Marketing, Buying and Advertising? October 26, 2015 Russell O’Sullivan 11 Comments Unless you have been hiding under a rock for about a year or so, no doubt you would have heard of programmatic marketing or advertising being bounded around by agencies, blog posts, in conferences and from those who want to target more efficient spend in the advertising arena. The IAB estimates that by 2018 programmatic spend will have grown from 28% in 2013 to over 80% of marketing spend. Its time to jump onboard and think about where and how you’ll be spending your digital budget. Programmatic buying will make up $14.88Bn of the approximately $58.6Bn digital advertising pie this…Click To Tweet This post will give you a high level – whistle stop tour of what is programmatic. How it is projected as a “game changer” in digital advertising budget changes and how it can benefit you. What is Programmatic marketing? Simply put – programmatic marketing is a way to target what types of audience you wish show your advertising to. Which can encompass segments across demographics such as age, gender, social standing, to geographic in certain areas of the country. As with Paid Search you can also limit the ads to times of day and frequency. You can decide which publishers you want your ads to show on. This way you are only paying for highly effective ads, delivered to the right people at the right time.

Automating the process means that it can be done in real time and doesn’t rely on the human touch, manual insertions and manual trading. Programmatic media buying allows the “owner/brand” to tailor a specific message and creative to the right person, at the right time in the right context – using audience insight from the brand (the customers you want to target) around the kind of audience they want to target. This methodology should deliver far more precision and personalization of messaging and media, resulting in more efficiently targeted campaigns, and less of the “spray and pray” methodology of digital advertising – which is less targeted and based on sheer volume (mainly of impressions). (img: http://www.forbes.com/sites/steveolenski/2015/09/18/the-current-state-of-programmatic-advertising/)How is Programmatic Marketing different? Again keeping this high level (as you will hear lots about Saa S, DSP, DMP etc which I will not go into here) programmatic marketing is about driving efficiencies in spend and resource. Ad buyers manually buy digital ads space (inventory) for their clients, so again, using the human touch. Programmatic makes the buying, placement and optimisation of process more efficient as its done by computers and algorithms – removing some of the mundane areas of dealing with different tagging requests, insertion orders and hopefully it should cut down on time to market too. What about Programmatic RTB (Real-time buying)? Programmatic RTB is different to PPC – as its done for display advertising only. Again its an automated way in transacting media thats bought and sold via technology platforms in Real-time. The process of RTB is set, so sellers of the ad space (publishers) make the space available for buyers (brands/advertisers) who then bid for that ad space. The RTB part comes into play, where brands/advertisers set different variables such as price, audience segment profiles (types of people) they are trying to reach with their message and the overall network reach. But how does it work in real life? When a webpage is being loaded and has the space for an advert (and there aren’t many that don’t serve ads of some kind eh) on it, information that’s been gathered about both the user/visitor (audience segment based on web behaviour etc) and the context of the site or webpage its being loaded to, is sent back and forth to an ad exchange and the ad is placed on that page. This space gets auctioned off to the highest bidder and their ad is placed in the space – all of this is done in milliseconds with no apparent detriment to page loads times or user experience. How do I know if an advert is programmatic or “normal display”? Well, you kind of don’t! Not 100% anyway, next time you see an advert on a web page – take a second or two to look at it and think, is it a targeted advert based on programmatic about you, your segment and likelihood to be an ideal person to click on it – or is it just inventory purchased on a spray and pray display – where volume or spreading the message as far and wide as possible, will drive the traffic or conversions your way. Is programmatic marketing the future of all advertising? As a person who works client side, then isn’t it right that we would want our advertising and campaigns to be marketed to the right type of person, at the right time for them in the context and place that they digest their media? Then my answer is yes!Programmatic marketing is moving quickly into the realms TV, radio and out of home (OOH) advertising, its not quite there in terms of display advertising just yet, but all of the background data that supports those media outlets is already there, it just needs to be used and “welcomed” by publishers – but it certainly will be very soon!I still believe there is a place for the “old inventory display” way of buying ad space, that could be used for more brand awareness – in terms of having a brand that offers lots of different products to different audiences. For me, I will be focusing my planning on programmatic!ALSO READ: How to get started with Programmatic advertising: A beginners guide Your Guide to Getting Started with Programmatic Marketing Looking to find out more about Programmatic Marketing? Sign up and download our FREE starters guide to programmatic marketing! A quick guide in which you can find the what, why and how to programmatic marketing. Your name *First Last Your E-mail *Posted Under Advertising Tagged advertising