More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
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Our breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
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“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
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Additionally, each book published by IntechOpen contains original content and research findings.
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We are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\n
Simba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
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IntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\n
Since the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\n
Our breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n
“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\n
Additionally, each book published by IntechOpen contains original content and research findings.
\n\n
We are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n
\n\n
\n'}],latestNews:[{slug:"stanford-university-identifies-top-2-scientists-over-1-000-are-intechopen-authors-and-editors-20210122",title:"Stanford University Identifies Top 2% Scientists, Over 1,000 are IntechOpen Authors and Editors"},{slug:"intechopen-authors-included-in-the-highly-cited-researchers-list-for-2020-20210121",title:"IntechOpen Authors Included in the Highly Cited Researchers List for 2020"},{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"},{slug:"oiv-awards-recognizes-intechopen-s-editors-20201127",title:"OIV Awards Recognizes IntechOpen's Editors"},{slug:"intechopen-joins-crossref-s-initiative-for-open-abstracts-i4oa-to-boost-the-discovery-of-research-20201005",title:"IntechOpen joins Crossref's Initiative for Open Abstracts (I4OA) to Boost the Discovery of Research"},{slug:"intechopen-hits-milestone-5-000-open-access-books-published-20200908",title:"IntechOpen hits milestone: 5,000 Open Access books published!"},{slug:"intechopen-books-hosted-on-the-mathworks-book-program-20200819",title:"IntechOpen Books Hosted on the MathWorks Book Program"}]},book:{item:{type:"book",id:"7636",leadTitle:null,fullTitle:"Wind Solar Hybrid Renewable Energy System",title:"Wind Solar Hybrid Renewable Energy System",subtitle:null,reviewType:"peer-reviewed",abstract:"This book provides a platform for scientists and engineers to comprehend the technologies of solar wind hybrid renewable energy systems and their applications. 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\n\t\t\t
1. Introduction
\n\t\t\t
Chromosomal aberration is a phenomenon occurring relatively commonly in the development process. Chromosomal aberration is known to have various causes, and its frequency has been reported to vary particularly according to maternal age. Though different among reports, the frequency was around 0.6-0.8% in analysis with all childbirths\n\t\t\t\t\t1\n\t\t\t\t and around 2-3% in case childbirths were reclassified based on maternal age of 35.\n\t\t\t\t\t2\n\t\t\t\t In addition, the frequency increased when the maternal age was relatively young, artificial insemination was used, etc.\n\t\t\t\t\t3\n\t\t\t\t Spontaneous abortion related to such chromosomal aberrations occurs usually in the first trimester, and consequently, the prevalence of trisomy 21, 18 and 13 decreases with the advance of gestational age.\n\t\t\t\t\t4\n\t\t\t\t Chromosomal aberrations that can be found in prenatal diagnosis are largely divided into aneuploidy, structural aberration, mosaicism, uniparental disomy, small defect, etc., and additionally, there can be marker chromosomes. Marker chromosomes are observed in around one out of 1000 cases of chromosomal analysis, and are known to be related to old maternal age.\n\t\t\t\t\t5\n\t\t\t\t It is reported that around 80% of marker chromosomes detected are new ones, and 13% of marker chromosomes are associated with physical abnormalities or cognitive disorders.\n\t\t\t\t\t6\n\t\t\t\t\n\t\t\t
\n\t\t\t
The frequency and type of chromosomal aberration are known to be different depending on the time of evaluation, population group under the analysis of structural chromosomal aberration, and the banding level of the laboratory performing cytogenetic evaluation.\n\t\t\t\t\t7\n\t\t\t\t Thus, it is increasingly important to conduct adequate prenatal genetic screening and analyze its results properly. Among chromosomal aberrations detected in pregnant women who received amniocentesis because of their age, 64% were trisomy (21% trisomy 21), 11% translocation, 17% sex chromosomal aberration, and 8% other types of chromosomal aberration.\n\t\t\t\t\t2\n\t\t\t\t Thus, considering the increasing number of old age pregnancies in Korea, careful attention should to paid in analyzing the results of prenatal genetic tests. Thus, this study purposed to discuss how to analyze the results of maternal serum marker tests and sonography used in prenatal genetic evaluation.
\n\t\t
\n\t\t
\n\t\t\t
2. Maternal serum screening
\n\t\t\t
\n\t\t\t\t
2.1. Alpha fetoprotein
\n\t\t\t\t
Brock and Sutcliffe found in 1972 that the level of alpha fetoprotein in amniotic fluid increased when the fetus had a neural tube defect, and from the 1980s, the maternal serum alpha fetoprotein test began to be used for screening fetal anomalies in pregnant women.
\n\t\t\t\t
Alpha fetoprotein, which is glycoprotein, is produced in the yolk sac in the early stage, and later in the fetal gastrointestinal tract and liver. A small portion of alpha fetoprotein in fetal serum may be discharged to urine and amniotic fluid, and it may diffuse through the fetal membrane and the placenta and enter maternal serum. Whereas the alpha fetoprotein level in fetal serum and amniotic fluid increases until 13 week and then decreases thereafter, the level in maternal serum increases continuously until 32 week because the size of the fetus keeps growing.\n\t\t\t\t\t\t8\n\t\t\t\t\t Between 16-20 week of gestational age, the level of alpha fetoprotein in maternal serum is only around 1/100,000 of that in fetal serum.
\n\t\t\t\t
\n\t\t\t\t\t
2.1.1. Analysis of serum alpha fetoprotein data
\n\t\t\t\t\t
As is known, the concentration of alpha fetoprotein in maternal serum or amniotic fluid is measured as a test for screening fetal neural tube defects. When the measurements of alpha fetoprotein are analyzed, we should be careful not to attach clinical importance to absolute values. It is because the test method of each laboratory or company may seem to have been stabilized by itself, but absolute values from the method are often different from those obtained by other laboratories or test methods. For this reason, the measurements of alpha fetoprotein are often reported as the multiples of the median (MoM). A median is the value in the middle when result values are put in order of size, so it can reduce errors and allow the comparative analysis of result values without being influenced by laboratory or test method.
\n\t\t\t\t\t
On the other hand, the measurements of alpha fetoprotein in maternal serum can be affected not only by multiple pregnancy and gestational age but also by maternal weight, diabetes, race, etc.\n\t\t\t\t\t\t\t9\n\t\t\t\t\t\t\n\t\t\t\t\t\t,\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t10\n\t\t\t\t\t\t, so these factors should be confirmed before the analysis of such measurements. Because the absolute level of serum alpha fetoprotein rises along with gestational age\n\t\t\t\t\t\t\t8\n\t\t\t\t\t\t, underestimated gestational age is the most common cause of increased alpha fetoprotein concentration. In such a case, we can avoid unnecessary additional tests by correcting gestational age and recalculating the median.
\n\t\t\t\t
\n\t\t\t\t
\n\t\t\t\t\t
2.1.2. Causes of increased alpha fetoprotein in maternal serum
\n\t\t\t\t\t
Fetal anomalies
\n\t\t\t\t\t
The rise of the alpha fetoprotein level in maternal serum is often accompanied by fetal anomalies. This is not because of a special function of alpha fetoprotein but because fetal tissue leaks to amniotic fluid due to neural tube defect, abdominal wall defect, sacrococcygeal teratoma, cystic hygroma, skin defect, etc. and, as a result, an increasing amount of alpha fetoprotein flows into amniotic fluid and maternal serum\n\t\t\t\t\t\t\t11\n\t\t\t\t\t\t or because alpha fetoprotein is not reabsorbed but discharged to urine due to fetal kidney anomaly.\n\t\t\t\t\t\t\t12\n\t\t\t\t\t\t\n\t\t\t\t\t
\n\t\t\t\t\t
In fetal neural tube defect, alpha fetoprotein exudes through exposed nervous tissue, so the level of alpha fetoprotein in maternal serum is relatively higher in spina bifida aperta or anencephaly than in spina bifida occulta. In most laboratories, those whose median alpha fetoprotein level in maternal serum is over 2.0-2.5 are classified into a high-risk group of fetal neural tube defect. When median 2.5 was used, spina bifida aperta was detected at a detection rate of 80% and the false positive rate was 3-4%.\n\t\t\t\t\t\t\t13\n\t\t\t\t\t\t\n\t\t\t\t\t
\n\t\t\t\t\t
The anomaly found second most commonly to neural tube defect in alpha-fetoprotein screening is abdominal wall defect. Particularly in case of gastroschisis, organs removed out of the abdominal cavity contact amniotic fluid directly, and therefore, the alpha fetoprotein level tends to be higher than that in omphalocele.\n\t\t\t\t\t\t\t11\n\t\t\t\t\t\t Maternal serum alpha fetoprotein screening detects around 85% of gastroschisis and around 50 % of omphalocele.\n\t\t\t\t\t\t\t11\n\t\t\t\t\t\t\n\t\t\t\t\t
Placental abnormalities
Because the concentration of alpha fetoprotein in fetal serum is 100,000 times higher than that in maternal serum\n\t\t\t\t\t\t\t8\n\t\t\t\t\t\t, even a small inflow of fetal blood increases the fetoprotein level in maternal serum rapidly. In case of chorioangioma in the placenta and hemangioma in the umbilical cord, fetal serum exudes into amniotic fluid and the maternal body due to mass bleeding\n\t\t\t\t\t\t\t14\n\t\t\t\t\t\t, and in case of placenta accreta, placental infarct, etc. as well, alpha fetoprotein increases in the same way.\n\t\t\t\t\t\t\t16\n\t\t\t\t\t\t\n\t\t\t\t\t
\n\t\t\t\t
\n\t\t\t
\n\t\t\t
\n\t\t\t\t
2.2. Maternal serum test for aneuploidy screening
\n\t\t\t\t
\n\t\t\t\t\t
2.2.1. Second trimester multiple marker screening test
\n\t\t\t\t\t
In 1984, Merkatz et al.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t16\n\t\t\t\t\t\t found that the risk of Down syndrome was high when the level of serum alpha fetoprotein was low during the second trimester, but this finding alone was not sufficient for using alpha fetoprotein as an accurate Down syndrome marker.\n\t\t\t\t\t\t\t16\n\t\t\t\t\t\t Later, double marker test that added human chorionic gonadotropin (hCG) test, and triple test that added also estriol (E3) to the double test were introduced as Down syndrome screening tests in the second trimester.\n\t\t\t\t\t\t\t18\n\t\t\t\t\t\t Recently, quad test that added inhibin A was developed\n\t\t\t\t\t\t\t18\n\t\t\t\t\t\t for higher accuracy of screening. The mean median (MoM) of each marker in trisomy 21 and 18 is presented in Table 1. There were large-scale prospective studies that compared accuracy among a number of multiple markers in the U.K. (Serum, Urine and Ultrasound Screening Study; SURUSS)\n\t\t\t\t\t\t\t19\n\t\t\t\t\t\t and the U.S. (First and Second Trimester Evaluation of Risk for Fetal Anueploidy; FASTER),\n\t\t\t\t\t\t\t20\n\t\t\t\t\t\t and in both studies the detection rate of quad markers was reported to be 81 %. Table 2 summarized the Down syndrome detection rates of multiple markers from the two studies.
\n\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t\tAneuploidy\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t\tAFP\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t\thCG\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t\tuE3\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t\tInhibin A\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t\tTrisomy 21\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
0.74 * (↓)
\n\t\t\t\t\t\t\t\t
2.05 * (↑)
\n\t\t\t\t\t\t\t\t
0.70 * (↓)
\n\t\t\t\t\t\t\t\t
2.548 * (↑)
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t\tTrisomy 18\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
0.65** (↓)
\n\t\t\t\t\t\t\t\t
0.32** (↓)
\n\t\t\t\t\t\t\t\t
0.42** (↓)
\n\t\t\t\t\t\t\t\t
-
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t
Table 1.
AFP, α-fetoprotein; hCG, human chorionic gonadotropin; uE3, unconjugated estriol* Modified from the results of the FASTER trial** Modified from the results of Benn PA et al. Obstet Gyenecol 1999;93:707-11. The mean MoM (multiples of the median) values for the second trimester maternal serum quad markers.
\n\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t\tDetection rate at a 5% false-positive rate\n\t\t\t\t\t\t\t\t
AFP, α-fetoprotein; hCG, human chorionic gonadotropin; uE3, unconjugated estriolThe detection rate of second trimester serum markers for Down syndrome.
\n\t\t\t\t
\n\t\t\t\t
\n\t\t\t\t\t
2.2.2. First trimester screening test
\n\t\t\t\t\t
Maternal serum triple marker test
\n\t\t\t\t\t
Among first trimester serum markers, pregnancy-associated plasma protein A (PAPP-A) and free β-hCG are known to have the highest discrimination for haploidy. In Down syndrome, the MoM of maternal serum PAPP-A is 0.38, decreasing by 60%, and that of free β-hCG is 1.83, increasing by around two times.\n\t\t\t\t\t\t\t21\n\t\t\t\t\t\t Accordingly, both of the two markers are used in first trimester screening, and with this test, the Down syndrome detection rate is 60-74% and the false positive rate is 5%.\n\t\t\t\t\t\t\t19\n\t\t\t\t\t\t\n\t\t\t\t\t\t,\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t20\n\t\t\t\t\t\t The detection rate is lower than that of the quad test in the second trimester but similar to that of the triple test.
\n\t\t\t\t\t
Nuchal translucency measuring
\n\t\t\t\t\t
The thickness of nuchal translucency in the first trimester is related to fetal haploidy, in particular, to Down syndrome, apart from maternal serum markers.\n\t\t\t\t\t\t\t22\n\t\t\t\t\t\t Accordingly, the accuracy of screening can be enhanced through the first trimester combined test that measures the thickness of nuchal translucency in addition to serologic tests that measure PAPPA-A and free β-hCG.\n\t\t\t\t\t\t\t22\n\t\t\t\t\t\t In the results of a meta-analysis with 209,603 subjects, the combined screening test showed a detection rate of 86% (84-88 95%, CI) with a false positive rate of 5.1% and Down syndrome was detected in 785 subjects.\n\t\t\t\t\t\t\t23\n\t\t\t\t\t\t When only nuchal translucency was measured without serologic tests, the Down syndrome detection rate was 77% with a false positive rate of 6.0%, so it was less accurate than the combined test. The positive predictive value of the combined screening test was 16.8 (16.3-17.4, 95% CI), which means that one out of 17 pregnancies with a positive result of the combined screening test is found to have a Down syndrome fetus.\n\t\t\t\t\t\t\t23\n\t\t\t\t\t\t On the other hand, because PAPP-A decreases but free β-hCG increases for 11-14 weeks of pregnancy, the detection rate varies significantly according to gestational age.\n\t\t\t\t\t\t\t23\n\t\t\t\t\t\t In the results of FASTER, the Down syndrome detection rate was 73% and the false positive rate was 1% in 11 weeks of pregnancy, but 67% and 5%, respectively, in 13 weeks, and based on this result the research reported that the accuracy of the combined test was highest at the gestational age of 11 weeks.\n\t\t\t\t\t\t\t20\n\t\t\t\t\t\t However, it was reported that if second trimester screening would be performed additionally, it would be more efficient to have the combined test in 10 weeks of pregnancy.\n\t\t\t\t\t\t\t23\n\t\t\t\t\t\t\n\t\t\t\t\t
\n\t\t\t\t
\n\t\t\t\t
\n\t\t\t\t\t
2.2.3. First and second trimester integrated test
\n\t\t\t\t\t
\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\tWald et al.\n\t\t\t\t\t\t\t\n\t\t\t\t\t\tproposed integrated test, which uses information on first and second trimester markers in sequence. They expected that if nuchal translucency and serum PAPP-A are measured in 10-13 weeks, and alpha fetoprotein, total hCG, estriol and inhibin A in 15-18 weeks, Down syndrome can be detected at a rate of 94% with a false positive rate of 5%, or 85% with a false positive rate of 1%.\n\t\t\t\t\t\t\t25\n\t\t\t\t\t\t Accordingly, because Down syndrome can be screened with a false positive rate of 1%, it reduces the need of additional diagnoses such as amniocentesis, and prevents fetal death resulting from invasive examination. In the results of SURUSS\n\t\t\t\t\t\t\t19\n\t\t\t\t\t\t and FASTER,\n\t\t\t\t\t\t\t20\n\t\t\t\t\t\t the integrated test was most accurate as a Down syndrome screening test (Table 3).
\n\t\t\t\t\t
However, the integrated test has a number of shortcomings to be an alternative general screening test in prenatal examination. First, most of pregnant women who receive a screening test in the first trimester want the termination of pregnancy immediately if abnormalities are found in the fetus, and it is safer to terminate pregnancy in the first trimester. Second, it is hard to distinguish pregnant women who cannot be followed up after first trimester serologic tests. In SURUSS \n\t\t\t\t\t\t\t19\n\t\t\t\t\t\t as well, 20% of pregnant women who had a first trimester test did not appear in the second trimester test. In such a case, there could be the legal risk of not telling the results of the first trimester test, so it was not an adequate alternative at present. Third, if the risk is unusually high in the results of the first trimester test the results are not provided until the second trimester, and this may raise an ethical issue. Thus, the integrated test can be the method of highest sensitivity and specificity if a pregnant woman receives prenatal examination from the beginning of pregnancy and takes both the first and second trimester screening tests, but is not adequate for those who want to get invasive chorionic villus sampling immediately based on the results of the first trimester screening test.
DR, detection rate; FPR, false positive rate; NT, nuchal translucency; PAPP-A, pregnancy associated plasma protein-A; f-βhCG free beta subunit of human chorionic gonadotropin; Quad, second trimester quadruple screen; AFP, alphafetoprotein; uE3, unconjugated estriol† Combined: NT, PAPP-A, and f-βhCG in the first trimester‡ Serum integrated: PAPP-A in the first trimester and quad screen in the second trimester§ Full integrated: NT and PAPP-A in the first trimester with quad screen in the second trimesterData from Rosen T et al. Semin Perinatol 2005;29:367-75.Direct comparative data for the first and second trimester Down syndrome screens from the prospective FASTER and SURUSS trials.
\n\t\t\t\t
\n\t\t\t\t
\n\t\t\t\t\t
2.2.4. Alternatives to the integrated test
\n\t\t\t\t\t
Sequential screening
\n\t\t\t\t\t
If the result of the first trimester screening test is positive, chromosomal analysis is performed immediately and if the result is negative, the second trimester screening test is performed and if the result is positive, chromosomal analysis is performed. A characteristic of this method is that the result of the first trimester screening test is provided to the pregnant woman and then the second trimester test is performed additionally. It can enhance the Down syndrome detection rate up to 98% but its false positive rate is also high as 17%.\n\t\t\t\t\t\t\t26\n\t\t\t\t\t\t\n\t\t\t\t\t
\n\t\t\t\t\t
Contingency screening
\n\t\t\t\t\t
If the first trimester screening test indicates high risk, chromosomal analysis is performed, and if the result indicates low risk no additional test is performed, but if it indicates moderate risk integrating screening is performed.\n\t\t\t\t\t\t\t27\n\t\t\t\t\t\t\n\t\t\t\t\t
\n\t\t\t\t
\n\t\t\t
\n\t\t
\n\t\t
\n\t\t\t
3. Genetic sonographic markers of aneuploidy
\n\t\t\t
Most of fetuses with chromosomal aberration have organs whose appearance is anomalous or abnormal, and such defects can be detected through prenatal sonography. A fetal structural anomaly may be caused by multiple factors, but it can be the result of chromosomal aberration. Therefore, if a fetal anomaly has been found, we should determine whether to perform cytogenetic analysis through amniocentesis after checking if other abnormalities accompany. Using genetic sonographic findings, we can detect pregnancies with high risk of aneuploidy at a sensitivity of 50-93%\n\t\t\t\t\t28\n\t\t\t\t, and the absence of genetic sonographic findings may be regarded as sure evidence for the low risk of haploidy. Genetic sonographic findings can be divided into major structural anomalies and minor anomalies. In particular, anomalies that are observed frequently also in normal fetuses and occasionally disappear with the advance of gestational age are called sonographic markers. It is generally accepted that a major anomaly is a sign of high risk of chromosomal aberration and thus chromosomal analysis is required, but it is still controversial whether additional tests are required when only a minor anomaly has been found. It is important to determine in consideration of the likelihood of chromosomal aberration on a case basis rather than applying a uniform rule to every case, and for this, we need to be familiar with the risk of chromosomal aberration and representative types of haploidy in connection to each genetic sonographic marker (Table 4).
\n\t\t\t
\n\t\t\t\t
3.1. Major anomalies related to haploidy
\n\t\t\t\t
The characteristic and frequency of sonographic findings in fetuses with chromosomal aberration are various according to gestational age, and the detection of abnormal findings is affected by the reason of sonography, criteria for positive finding, the level of sonographic equipment, etc. Structural major anomalies are detected mostly by sonography in trisomy 13 and 18, but are missed relatively often in trisomy 21. Table 5 summarized structural major anomalies detected commonly in pregnancies with trisomy 13, 18 and 21 and Turner syndrome.
\n\t\t\t
\n\t\t\t
\n\t\t\t\t
3.2. Sonographic markers related to haploidy
\n\t\t\t\t
The most common sonographic markers in the second trimester include nuchal thickening, hyperechoic bowel, short limbs, pyelectasia, echogenic intracardiac focus, and choroid plexus cysts. In general, the risk of chromosomal aberration is higher when the number of markers is large. Table 6 summarized the likelihood ratio of haploidy when each sonographic marker has occurred singly. The likelihood ratio was calculated by sensitivity / false positive rate, and if two or more sonographic markers have occurred together, the combined likelihood ratio is the product of their respective likelihood ratios.
B, birth; EU, early ultrasonography; LB, livebirth; IA, infant autopsy.Data from Shipp TD, et al. Am J Obstet Gynecol 1998; 178: 600–2. and Nyberg DA and Crane JP. Chromosome abnormalities. In: Nyberg DA, et al. Diagnostic ultrasound of fetal anomalies: text and atlas. Chicago (IL): Year Book Medical; 1990. p. 676–724.Aneuploidy risk of major structural fetal malformation.
Heart (Coarctation of aorta) Abnormal fluid accumulation (increased nuchal translucency/ thickened nuchal fold, cystic hygroma, feta hydrops) Renal anomalies Short femur or humerus
\n\t\t\t\t\t\t
\n\t\t\t\t\t
Table 5.
CNS, central nervous system; IUGR, intrauterine growth restriction; VSD, ventricular septal defectSonographic finding with high incidence in different fetal chromosomal abnormalities
\n\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\tLikelihood ratio (95% confidence interval)\n\t\t\t\t\t\t\t
Data from Nyberg DA, et al Ultrasound Obstet Gynecol 1998; 12: 8-14. and Smith-Bindman R et al. JAMA. 2001; 285: 1044-55.Likelihood ratio of sonographic soft marker for fetal aneuploidy
\n\t\t\t\t
\n\t\t\t\t\t
3.2.1. Choroid plexus cysts
\n\t\t\t\t\t
Choroid plexus cyst is found relatively commonly during the second trimester, showing a prevalence of 0.3-3.6%.\n\t\t\t\t\t\t\t29\n\t\t\t\t\t\t This type of cyst is known to be benign, disappearing spontaneously at the later stage of pregnancy without affecting the development of the fetus. As a sonographic marker of haploidy, choroid plexus cyst is found in 50% of fetuses with trisomy 18\n\t\t\t\t\t\t\t30\n\t\t\t\t\t\t but most of the cases are accompanied by another anomaly, and it is reported that no particular prenatal care including chromosomal analysis is necessary if only isolated choroid plexus cysts are found.\n\t\t\t\t\t\t\t29\n\t\t\t\t\t\t\n\t\t\t\t\t
\n\t\t\t\t
\n\t\t\t\t
\n\t\t\t\t\t
3.2.2. Mild cerebral ventricular dilatation
\n\t\t\t\t\t
Mild cerebral ventricular dilatation, in which the diameter of the cerebral lateral ventricle is over 10-15 mm, is related to aneuploidy like trisomy 21.\n\t\t\t\t\t\t\t32\n\t\t\t\t\t\t\n\t\t\t\t\t\tBromley et al.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t32\n\t\t\t\t\t\t reported that 12% of pregnancies with mild cerebral ventricular dilatation are related to abnormal karyotype (trisomy 18, 21). In addition, mild cerebral ventricular dilatation was observed in 4.3% of fetuses with trisomy 21\n\t\t\t\t\t\t\t33\n\t\t\t\t\t\t and all of them had accompanying anomalies. It is known that the presence of cerebral ventricular dilatation alone does not increase the risk of chromosomal aberration.
\n\t\t\t\t
\n\t\t\t\t
\n\t\t\t\t\t
3.2.3. Nuchal thickening
\n\t\t\t\t\t
Excessive skin on the back neck is a characteristic finding of trisomy 21. It is observed in 80% of neonates with trisomy 21 and can be found in other chromosomal aberrations (trisomy 13 and 18, 45X).\n\t\t\t\t\t\t\t34\n\t\t\t\t\t\t Although the sensitivity and the false positive rate vary according to gestational age and criteria for positive value are different among institutions, its sensitivity for detecting chromosomal aberrations is generally within the range of 20-40%.
\n\t\t\t\t
\n\t\t\t\t
\n\t\t\t\t\t
3.2.4. Hyper-echoic bowel
\n\t\t\t\t\t
Hyper-echoic bowel is found in 0.5% of normal fetuses, but in fetuses with aneuploidy like trisomy 21, it is known to be observed more frequently and increase the risk 6-7 times higher.\n\t\t\t\t\t\t\t35\n\t\t\t\t\t\t Assuming that the likelihood ratio of isolated hyper-echoic bowel is 6.7 and the total risk of Down syndrome in the entire population is one per 500, isolated echoic bowel is expected to be related to the risk of Down syndrome in around 1-2% of the general population. Hyper-echoic bowel is also known to be related to ileus, congenital infection, and rarely to secondary meconium ileus in cystic fibrosis.\n\t\t\t\t\t\t\t36\n\t\t\t\t\t\t\n\t\t\t\t\t
\n\t\t\t\t
\n\t\t\t\t
\n\t\t\t\t\t
3.2.5. Skeletal abnormalities such as shortened limbs
\n\t\t\t\t\t
Shortened limbs are a characteristic observed in fetuses with trisomy 21\n\t\t\t\t\t\t\t37\n\t\t\t\t\t\t and the length of shortened humerus seems to be a slightly more specific marker than the length of shortened femur. These results may be different according to gestational age, racial group, expected sex of the fetus, and used criteria.
\n\t\t\t\t
\n\t\t\t\t
\n\t\t\t\t\t
3.2.6. Echogenic intracardiac focus
\n\t\t\t\t\t
Echogenic intracardiac focus is a common finding in the second trimester. It is observed in 3-4% of normal fetuses and disappears spontaneously in the third trimester. If the size of echogenic intracardiac focus is large or there are multiple of them, the risk of aneuploidy increases. Bromley et al. reported that the risk of aneuploidy is 2 times higher when echogenic intracardiac focuses are in the right ventricle or bilateral than when they are only in the left ventricle.
\n\t\t\t\t
\n\t\t\t
\n\t\t
\n\t\t
\n\t\t\t
4. Conclusions
\n\t\t\t
Chromosomal aberration is closely related to the in intrauterine fetal death and perinatal prevalence. However, amniocentesis and chorionic villus sampling used for prenatal diagnosis of haploidy are invasive methods, and the reported fetal loss rate resulting just from the examinations is around 1-2%. Accordingly, it is very important to screen those with high risk of chromosomal aberration before such invasive examinations.
\n\t\t\t
Serologic test of pregnant women for the screening of trisomy 18 and 21 is an important diagnostic process in prenatal care, and in particular, second trimester serum alpha fetoprotein is used as an important screening marker to detect anomalies such as fetal neural tube defect. If the concentration of alpha fetoprotein is over 2.5 MoM, sonography should be performed in order to detect neural tube defect and other problems. Recently, because sonography shows a high detection rate for neural tube defect, amniocentesis is used less frequently in diagnosing neural tube defect.
\n\t\t\t
The preferred type of serum screening test is various among countries and institutions. In general, the first trimester screening test is increasingly preferred, but second trimester screening is still used frequently at hospitals that cannot measure fetal nuchal translucency or perform chorionic villus sampling. The triple test has been used commonly as second trimester screening, but recently the use of the quad test, which adds inhibin A, is increasing. If both first and second trimester tests are performed, they can increase the detection rate of fetal anomalies, but because the two tests have to be applied at an interval of 3-4 weeks, it is quite important to provide an adequate explanation to the patient. The serum screening test can be performed in various ways depending on the combination of serum factors. Thus, rather than using a uniform test for every case, we need to understand the characteristic, detection rate and false positive rate of each test, and individualize the test for each case according to maternal age, sonographic findings, and compliance.
\n\t\t\t
In conclusion, in order to determine the risk of chromosomal aberration, we should analyze each case based on maternal age, nuchal fold thickness in the first trimester, the results of maternal serum screening in the first or second trimester, and sonographic findings in the second trimester. Through this approach, we may reduce the number of unnecessary chromosomal analyses, lower the fetal loss rate resulting from invasive examination, and enhance the accuracy of screening for fetal chromosomal aberrations.
\n\t\t
\n\t\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/18451.pdf",chapterXML:"https://mts.intechopen.com/source/xml/18451.xml",downloadPdfUrl:"/chapter/pdf-download/18451",previewPdfUrl:"/chapter/pdf-preview/18451",totalDownloads:3425,totalViews:137,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,dateSubmitted:"October 20th 2010",dateReviewed:"May 6th 2011",datePrePublished:null,datePublished:"August 29th 2011",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/18451",risUrl:"/chapter/ris/18451",book:{slug:"genetics-and-etiology-of-down-syndrome"},signatures:"Myungshin Kim, Jong Chul Shin and In Yang Park",authors:[{id:"28289",title:"Dr.",name:"Myungshin",middleName:null,surname:"Kim",fullName:"Myungshin Kim",slug:"myungshin-kim",email:"microkim@catholic.ac.kr",position:null,institution:null},{id:"43194",title:"Prof.",name:"Jong Chul",middleName:null,surname:"Shin",fullName:"Jong Chul Shin",slug:"jong-chul-shin",email:"jcshin@catholic.ac.kr",position:null,institution:null},{id:"43195",title:"Dr.",name:"In Yang",middleName:null,surname:"Park",fullName:"In Yang Park",slug:"in-yang-park",email:"ooooobbbbb@catholic.ac.kr",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Maternal serum screening",level:"1"},{id:"sec_2_2",title:"2.1. Alpha fetoprotein",level:"2"},{id:"sec_2_3",title:"2.1.1. Analysis of serum alpha fetoprotein data",level:"3"},{id:"sec_3_3",title:"2.1.2. Causes of increased alpha fetoprotein in maternal serum",level:"3"},{id:"sec_5_2",title:"2.2. Maternal serum test for aneuploidy screening",level:"2"},{id:"sec_5_3",title:"Table 1.",level:"3"},{id:"sec_6_3",title:"2.2.2. First trimester screening test",level:"3"},{id:"sec_7_3",title:"Table 3.",level:"3"},{id:"sec_8_3",title:"2.2.4. Alternatives to the integrated test",level:"3"},{id:"sec_11",title:"3. Genetic sonographic markers of aneuploidy",level:"1"},{id:"sec_11_2",title:"3.1. Major anomalies related to haploidy ",level:"2"},{id:"sec_12_2",title:"3.2. Sonographic markers related to haploidy ",level:"2"},{id:"sec_12_3",title:"3.2.1. Choroid plexus cysts",level:"3"},{id:"sec_13_3",title:"3.2.2. Mild cerebral ventricular dilatation",level:"3"},{id:"sec_14_3",title:"3.2.3. Nuchal thickening",level:"3"},{id:"sec_15_3",title:"3.2.4. Hyper-echoic bowel",level:"3"},{id:"sec_16_3",title:"3.2.5. Skeletal abnormalities such as shortened limbs",level:"3"},{id:"sec_17_3",title:"3.2.6. Echogenic intracardiac focus",level:"3"},{id:"sec_20",title:"4. Conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNielsen\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWohlert\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\tChromosome abnormalities found among 34,910 newborn children: results from a 13-year incidence study in Arhus, Denmark. Hum Genet 1991\n\t\t\t\t\t87\n\t\t\t\t\t81\n\t\t\t\t\t3\n\t\t\t\t\n\t\t\t'},{id:"B2",body:'\n\t\t\t\t\n\t\t\t\t\tFerguson-Smith MA, Yates JR.Maternal age specific rates for chromosome aberrations and factors influencing them: report of a collaborative european study on 52,965 amniocenteses. 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V.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRodis\n\t\t\t\t\t\t\tJ. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBeazoglou\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCollins\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHorne\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\tMaternal serum screening for feta trisomy 18: a comparion of fixed cut off and patient-specific risk protocols. Obstet Gyenecol 1999\n\t\t\t\t\t93\n\t\t\t\t\t707\n\t\t\t\t\t11\n\t\t\t\t\n\t\t\t'},{id:"B22",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrizot\n\t\t\t\t\t\t\tM. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSnijders\n\t\t\t\t\t\t\tR. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tButler\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBersinger\n\t\t\t\t\t\t\tN. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNicolaides\n\t\t\t\t\t\t\tK. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMaternal\n\t\t\t\t\t\t\tserum. h. C. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tfetal\n\t\t\t\t\t\t\tnuchal.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\ttranslucency\n\t\t\t\t\t\t\tthickness.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tfor\n\t\t\t\t\t\t\tthe.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tprediction\n\t\t\t\t\t\t\tof.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tfetal\n\t\t\t\t\t\t\ttrisomies.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tin\n\t\t\t\t\t\t\tthe.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tfirst\n\t\t\t\t\t\t\ttrimester.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tof\n\t\t\t\t\t\t\tpregnancy.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBr\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tObstet\n\t\t\t\t\t\t\tGynaecol.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1995\n\t\t\t\t\t102\n\t\t\t\t\t127\n\t\t\t\t\t32\n\t\t\t\t\n\t\t\t'},{id:"B23",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRosen\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tME\n\t\t\t\t\t\t\tD’Alton\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\tDown syndrome screening in the first and second trimesters: what do the data show? Semin Perinatol 2005\n\t\t\t\t\t29\n\t\t\t\t\t367\n\t\t\t\t\t75\n\t\t\t\t\n\t\t\t'},{id:"B24",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBerry\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAitken\n\t\t\t\t\t\t\tD. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCrossley\n\t\t\t\t\t\t\tJ. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMacri\n\t\t\t\t\t\t\tJ. N.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tConnor\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\tScreening for Down’s syndrome: changes in marker levels and detection rates between first and second trimesters. Br J Obstet Gynaecol 1997\n\t\t\t\t\t104\n\t\t\t\t\t811\n\t\t\t\t\t7\n\t\t\t\t\n\t\t\t'},{id:"B25",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSpencer\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSouter\n\t\t\t\t\t\t\tV.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTul\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSnijders\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNicolaides\n\t\t\t\t\t\t\tK. H. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tscreening\n\t\t\t\t\t\t\tprogram.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tfor\n\t\t\t\t\t\t\ttrisomy. .\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tat\n\t\t\t\t\t\t\t10-.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tweeks\n\t\t\t\t\t\t\tusing.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tfetal\n\t\t\t\t\t\t\tnuchal.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\ttranslucency\n\t\t\t\t\t\t\tmaternal.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tserum\n\t\t\t\t\t\t\tfree.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tbeta-human\n\t\t\t\t\t\t\tchorionic.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tgonadotropin\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tpregnancy-associated\n\t\t\t\t\t\t\tplasma.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tprotein-A\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\tUltrasound Obstet Gynecol 1999\n\t\t\t\t\t13\n\t\t\t\t\t231\n\t\t\t\t\t7\n\t\t\t\t\n\t\t\t'},{id:"B26",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWapner\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tThom\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSimpson\n\t\t\t\t\t\t\tJ. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPergament\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSilver\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFilkins\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\tet al.\n\t\t\t\t\tFirst Trimester Maternal Serum Biochemistry and Fetal Nuchal Translucency Screening (BUN) Study Group.First-trimester screening for trisomies 21 and 18. N Engl J Med 2003\n\t\t\t\t\t349\n\t\t\t\t\t1405\n\t\t\t\t\t13\n\t\t\t\t\n\t\t\t'},{id:"B27",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCuckle\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBenn\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWright\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\tDown syndrome screening in the first and/or second trimester: model predicted performance using meta-analysis parameters. Semin Perinatol 2005\n\t\t\t\t\t29\n\t\t\t\t\t252\n\t\t\t\t\t7\n\t\t\t\t\n\t\t\t'},{id:"B28",body:'\n\t\t\t\t\n\t\t\t\t\tShipp TD, Benacerraf BR.Second trimester ultrasound screening for chromosomal abnormalities. Prenat Diagn 2002\n\t\t\t\t\t22\n\t\t\t\t\t296\n\t\t\t\t\t307\n\t\t\t\t\n\t\t\t'},{id:"B29",body:'\n\t\t\t\t\n\t\t\t\t\tYoder PR, Sabbagha RE, Gross SJ, Zelop CM.The second-trimester fetus with isolated choroid plexus cysts: a meta-analysis of risk of trisomies 18 and 21.Obstet Gynecol 1999Pt 2): 869-72.\n\t\t\t'},{id:"B30",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSnijders\n\t\t\t\t\t\t\tR. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShawa\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNicolaides\n\t\t\t\t\t\t\tK. H.\n\t\t\t\t\t\t\n\t\t\t\t\tFetal choroid plexus cysts and trisomy 18: assessment of risk based on ultrasound findings and maternal age. Prenat Diagn 1994\n\t\t\t\t\t14\n\t\t\t\t\t1119\n\t\t\t\t\t27\n\t\t\t\t\n\t\t\t'},{id:"B31",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVintzileos\n\t\t\t\t\t\t\tA. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAnanth\n\t\t\t\t\t\t\tC. V.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFisher\n\t\t\t\t\t\t\tA. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSmulian\n\t\t\t\t\t\t\tJ. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDay-Salvatore\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBeazoglou\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\tet al.\n\t\t\t\t\tAnanth CV, Fisher AJ, Smulian JC, Day-Salvatore D, Beazoglou T, et al. An economic evaluation of prenatal strategies for detection of trisomy 18. Am J Obstet Gynecol 1998\n\t\t\t\t\t179\n\t\t\t\t\t1220\n\t\t\t\t\t4\n\t\t\t\t\n\t\t\t'},{id:"B32",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBromley\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFrigoletto\n\t\t\t\t\t\t\tF. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJr Benacerraf\n\t\t\t\t\t\t\tB. R.\n\t\t\t\t\t\t\n\t\t\t\t\tMild fetal lateral cerebral ventriculomegaly: clinical course and outcome. Am J Obstet Gynecol 1991\n\t\t\t\t\t164\n\t\t\t\t\t863\n\t\t\t\t\t7\n\t\t\t\t\n\t\t\t'},{id:"B33",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNyberg\n\t\t\t\t\t\t\tD. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSouter\n\t\t\t\t\t\t\tV. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEl -Bastawissi\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYoung\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLuthhardt\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLuthy\n\t\t\t\t\t\t\tD. A.\n\t\t\t\t\t\t\n\t\t\t\t\tIsolated sonographic markers for detection of fetal Down syndrome in the second trimester of pregnancy. J Ultrasound Med 2001\n\t\t\t\t\t20\n\t\t\t\t\t1053\n\t\t\t\t\t63\n\t\t\t\t\n\t\t\t'},{id:"B34",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBorrell\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCosta\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMartinez\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDelgado\n\t\t\t\t\t\t\tR. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCasals\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOjuel\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\tet al.\n\t\t\t\t\tEarly midtrimester fetal nuchal thickness: effectiveness as a marker of Down syndrome. Am J Obstet Gynecol 1996\n\t\t\t\t\t175\n\t\t\t\t\t45\n\t\t\t\t\t9\n\t\t\t\t\n\t\t\t'},{id:"B35",body:'\n\t\t\t\t\n\t\t\t\t\tNyberg DA, Resta RG, Luthy DA, Hickok DE, Mahony BS, Hirsch JH.Prenatal sonographic findings of Down syndrome: review of 94 cases. Obstet Gynecol 1990Pt 1): 370-7.\n\t\t\t'},{id:"B36",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMuller\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDommergues\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAubry\n\t\t\t\t\t\t\tM. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSimon-Bouy\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGautier\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOury\n\t\t\t\t\t\t\tJ. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\tet al.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHyperechogenic\n\t\t\t\t\t\t\tfetal.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tbowel\n\t\t\t\t\t\t\tan.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tultrasonographic\n\t\t\t\t\t\t\tmarker.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tfor\n\t\t\t\t\t\t\tadverse.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tfetal\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tneonatal\n\t\t\t\t\t\t\toutcome.\n\t\t\t\t\t\t\n\t\t\t\t\tAm J Obstet Gynecol 1995\n\t\t\t\t\t173\n\t\t\t\t\t508\n\t\t\t\t\t13\n\t\t\t\t\n\t\t\t'},{id:"B37",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBenacerraf\n\t\t\t\t\t\t\tB. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNeuberg\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFrigoletto\n\t\t\t\t\t\t\tF. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJr \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\tHumeral shortening in second-trimester fetuses with Down syndrome.Obstet Gynecol 1991\n\t\t\t\t\t77\n\t\t\t\t\t223\n\t\t\t\t\t7\n\t\t\t\t\n\t\t\t'},{id:"B38",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBM\n\t\t\t\t\t\t\tPetrikovsky\n\t\t\t\t\t\t\tChallenger. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWyse\n\t\t\t\t\t\t\tL. J.\n\t\t\t\t\t\t\n\t\t\t\t\tNatural history of echogenic foci within ventricles of the fetal heart. Ultrasound Obstet Gynecol 1995\n\t\t\t\t\t5\n\t\t\t\t\t92\n\t\t\t\t\t4\n\t\t\t\t\n\t\t\t'},{id:"B39",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBromley\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLieberman\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShipp\n\t\t\t\t\t\t\tT. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRichardson\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBenacerraf\n\t\t\t\t\t\t\tB. R.\n\t\t\t\t\t\t\n\t\t\t\t\tSignificance of an echogenic intracardiac focus in fetuses at high and low risk for aneuploidy. J Ultrasound Med 1998\n\t\t\t\t\t17\n\t\t\t\t\t127\n\t\t\t\t\t31\n\t\t\t\t\n\t\t\t'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Myungshin Kim",address:"",affiliation:'
'},{corresp:null,contributorFullName:"In Yang Park",address:null,affiliation:'
The Catholic University of Korea, Seoul, Korea
'}],corrections:null},book:{id:"211",title:"Genetics and Etiology of Down Syndrome",subtitle:null,fullTitle:"Genetics and Etiology of Down Syndrome",slug:"genetics-and-etiology-of-down-syndrome",publishedDate:"August 29th 2011",bookSignature:"Subrata Dey",coverURL:"https://cdn.intechopen.com/books/images_new/211.jpg",licenceType:"CC BY-NC-SA 3.0",editedByType:"Edited by",editors:[{id:"31178",title:"Prof.",name:"Subrata",middleName:"Kumar",surname:"Dey",slug:"subrata-dey",fullName:"Subrata Dey"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"18436",title:"Genetics of Down Syndrome",slug:"genetics-of-down-syndrome",totalDownloads:4183,totalCrossrefCites:0,signatures:"Thomas Eggermann and Gesa Schwanitz",authors:[{id:"29551",title:"Prof.",name:"Thomas",middleName:null,surname:"Eggermann",fullName:"Thomas Eggermann",slug:"thomas-eggermann"},{id:"40492",title:"Prof.",name:"Gesa",middleName:null,surname:"Schwanitz",fullName:"Gesa Schwanitz",slug:"gesa-schwanitz"}]},{id:"18437",title:"Etiology of Down Syndrome: Risk of Advanced Maternal Age and Altered Meiotic Recombination for Chromosome 21 Nondisjunction",slug:"etiology-of-down-syndrome-risk-of-advanced-maternal-age-and-altered-meiotic-recombination-for-chromo",totalDownloads:4387,totalCrossrefCites:0,signatures:"Subrata Kumar Dey and Sujoy Ghosh",authors:[{id:"31178",title:"Prof.",name:"Subrata",middleName:"Kumar",surname:"Dey",fullName:"Subrata Dey",slug:"subrata-dey"},{id:"125697",title:"Prof.",name:"Sujoy",middleName:null,surname:"Ghosh",fullName:"Sujoy Ghosh",slug:"sujoy-ghosh"}]},{id:"18438",title:"Combinatorial Gene Effects on the Neural Progenitor Pool in Down Syndrome",slug:"combinatorial-gene-effects-on-the-neural-progenitor-pool-in-down-syndrome",totalDownloads:2442,totalCrossrefCites:0,signatures:"Jie Lu and Volney Sheen",authors:[{id:"40911",title:"Dr.",name:"Volney",middleName:null,surname:"Sheen",fullName:"Volney Sheen",slug:"volney-sheen"},{id:"47427",title:"Dr.",name:"Jie",middleName:null,surname:"Lu",fullName:"Jie Lu",slug:"jie-lu"}]},{id:"18439",title:"Down Syndrome: A Complex and Interactive Genetic Disorder",slug:"down-syndrome-a-complex-and-interactive-genetic-disorder",totalDownloads:2690,totalCrossrefCites:0,signatures:"Samantha L. Deitz, Joshua D. Blazek, Jeffrey P. Solzak and Randall J. Roper",authors:[{id:"31505",title:"Dr.",name:"Randall J.",middleName:null,surname:"Roper",fullName:"Randall J. Roper",slug:"randall-j.-roper"},{id:"45540",title:"Ms.",name:"Samantha L.",middleName:null,surname:"Deitz",fullName:"Samantha L. Deitz",slug:"samantha-l.-deitz"},{id:"45541",title:"Mr.",name:"Joshua D.",middleName:null,surname:"Blazek",fullName:"Joshua D. Blazek",slug:"joshua-d.-blazek"},{id:"45542",title:"Mr.",name:"Jeffrey P.",middleName:null,surname:"Solzak",fullName:"Jeffrey P. 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Ortez-González",authors:[{id:"31072",title:"Dr.",name:"Carlos",middleName:null,surname:"Ortez-González",fullName:"Carlos Ortez-González",slug:"carlos-ortez-gonzalez"},{id:"44771",title:"Dr.",name:"Andrés",middleName:null,surname:"Nascimento",fullName:"Andrés Nascimento",slug:"andres-nascimento"}]},{id:"18743",title:"Endocrine and Autonomic Nervous Adaptations during Physical Exercise in Down Syndrome",slug:"endocrine-and-autonomic-nervous-adaptations-during-physical-exercise-in-down-syndrome",totalDownloads:2631,totalCrossrefCites:0,signatures:"Véronique ~ Aurélie Bricout",authors:[{id:"29316",title:"Dr.",name:"Véronique-Aurelie",middleName:null,surname:"Bricout",fullName:"Véronique-Aurelie Bricout",slug:"veronique-aurelie-bricout"}]},{id:"18744",title:"Language and Visuospatial Abilities in Down Syndrome Phenotype: A Cognitive Neuroscience Perspective",slug:"language-and-visuospatial-abilities-in-down-syndrome-phenotype-a-cognitive-neuroscience-perspective",totalDownloads:2983,totalCrossrefCites:0,signatures:"George Grouios and Antonia Ypsilanti",authors:[{id:"39181",title:"Prof.",name:"George",middleName:null,surname:"Grouios",fullName:"George Grouios",slug:"george-grouios"},{id:"45480",title:"Dr.",name:"Antonia",middleName:null,surname:"Ypsilanti",fullName:"Antonia Ypsilanti",slug:"antonia-ypsilanti"}]},{id:"18451",title:"Prenatal Diagnosis of Down Syndrome",slug:"prenatal-diagnosis-of-down-syndrome",totalDownloads:3425,totalCrossrefCites:0,signatures:"Myungshin Kim, Jong Chul Shin and In Yang Park",authors:[{id:"28289",title:"Dr.",name:"Myungshin",middleName:null,surname:"Kim",fullName:"Myungshin Kim",slug:"myungshin-kim"},{id:"43194",title:"Prof.",name:"Jong Chul",middleName:null,surname:"Shin",fullName:"Jong Chul Shin",slug:"jong-chul-shin"},{id:"43195",title:"Dr.",name:"In Yang",middleName:null,surname:"Park",fullName:"In Yang Park",slug:"in-yang-park"}]},{id:"18452",title:"First Trimester Screening for Trisomy 21 by Maternal Age, Nuchal Translucency and Fetal Nasal Bone in Unselected Pregnancies",slug:"first-trimester-screening-for-trisomy-21-by-maternal-age-nuchal-translucency-and-fetal-nasal-bone-in",totalDownloads:4913,totalCrossrefCites:0,signatures:"Ksenija Gersak, Maja Pohar-Perme and Darija M. Strah",authors:[{id:"53853",title:"Prof.",name:"Ksenija",middleName:null,surname:"Gersak",fullName:"Ksenija Gersak",slug:"ksenija-gersak"},{id:"88543",title:"Dr.",name:"Maja",middleName:null,surname:"Pohar-Perme",fullName:"Maja Pohar-Perme",slug:"maja-pohar-perme"},{id:"88544",title:"M.D.",name:"Darija",middleName:"Mateja",surname:"Strah",fullName:"Darija Strah",slug:"darija-strah"}]},{id:"18453",title:"Noninvasive Prenatal Nucleic Acid Diagnostics of Down Syndrome",slug:"noninvasive-prenatal-nucleic-acid-diagnostics-of-down-syndrome",totalDownloads:2215,totalCrossrefCites:0,signatures:"Radek Vodicka, Radek Vrtel, Jana Böhmova, Romana Kratochvilova, Ladislav Dusek, Ishraq Dhaifalah and Jiri Santavy",authors:[{id:"34497",title:"Prof.",name:"Radek",middleName:null,surname:"Vrtel",fullName:"Radek Vrtel",slug:"radek-vrtel"},{id:"42497",title:"Dr.",name:"Radek",middleName:null,surname:"Vodicka",fullName:"Radek Vodicka",slug:"radek-vodicka"},{id:"42498",title:"MSc.",name:"Jana",middleName:null,surname:"Bohmova",fullName:"Jana Bohmova",slug:"jana-bohmova"},{id:"42499",title:"BSc.",name:"Romana",middleName:null,surname:"Kratochvilova",fullName:"Romana Kratochvilova",slug:"romana-kratochvilova"},{id:"42500",title:"Dr.",name:"Ladislav",middleName:null,surname:"Dusek",fullName:"Ladislav Dusek",slug:"ladislav-dusek"},{id:"42501",title:"Prof.",name:"Jiri",middleName:null,surname:"Santavy",fullName:"Jiri Santavy",slug:"jiri-santavy"},{id:"84361",title:"Dr.",name:"Ishraq",middleName:null,surname:"Dhaifalah",fullName:"Ishraq Dhaifalah",slug:"ishraq-dhaifalah"}]}]},relatedBooks:[{type:"book",id:"3298",title:"Down Syndrome",subtitle:null,isOpenForSubmission:!1,hash:"99ef7199bce28e844249e7591894caab",slug:"down-syndrome",bookSignature:"Subrata Kumar Dey",coverURL:"https://cdn.intechopen.com/books/images_new/3298.jpg",editedByType:"Edited by",editors:[{id:"31178",title:"Prof.",name:"Subrata",surname:"Dey",slug:"subrata-dey",fullName:"Subrata Dey"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"43371",title:"Down Syndrome: Clinical and Genetic Aspects, Genetic Counseling and Prenatal Screening and Diagnosis",slug:"down-syndrome-clinical-and-genetic-aspects-genetic-counseling-and-prenatal-screening-and-diagnosis",signatures:"Érika Cristina Pavarino, Joice Matos Biselli, Walter Pinto Junior and Eny Maria Goloni Bertollo",authors:[{id:"34736",title:"Prof.",name:"Érika Cristina",middleName:null,surname:"Pavarino",fullName:"Érika Cristina Pavarino",slug:"erika-cristina-pavarino"},{id:"45453",title:"MSc.",name:"Joice Matos",middleName:null,surname:"Biselli",fullName:"Joice Matos Biselli",slug:"joice-matos-biselli"},{id:"45454",title:"Prof.",name:"Eny Maria",middleName:null,surname:"Goloni Bertollo",fullName:"Eny Maria Goloni Bertollo",slug:"eny-maria-goloni-bertollo"},{id:"166057",title:"Dr.",name:"Walter",middleName:null,surname:"Pinto Júnior",fullName:"Walter Pinto Júnior",slug:"walter-pinto-junior"}]},{id:"41379",title:"Increased Fetal Nuchal Translucency Thickness and Normal Karyotype: Prenatal and Postnatal Outcome",slug:"increased-fetal-nuchal-translucency-thickness-and-normal-karyotype-prenatal-and-postnatal-outcome",signatures:"Ksenija Gersak, Darija M. 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Ordonez, Gabriel Fornieles, Alejandra Camacho, Miguel A. Rosety, Antonio J Diaz, Ignacio Rosety, Natalia Garcia and Manuel Rosety-Rodriguez",authors:[{id:"156546",title:"Dr",name:"Francisco Javier",middleName:null,surname:"Ordonez",fullName:"Francisco Javier Ordonez",slug:"francisco-javier-ordonez"}]},{id:"43380",title:"Heart Diseases in Down Syndrome",slug:"heart-diseases-in-down-syndrome",signatures:"A. K. M. Mamunur Rashid",authors:[{id:"156647",title:"Dr.",name:"A K M Mamunur",middleName:null,surname:"Rashid",fullName:"A K M Mamunur Rashid",slug:"a-k-m-mamunur-rashid"}]},{id:"43381",title:"Myeloid Leukemia Associated with Down Syndrome",slug:"myeloid-leukemia-associated-with-down-syndrome",signatures:"Kazuko Kudo",authors:[{id:"155649",title:"Dr.",name:"Kazuko",middleName:null,surname:"Kudo",fullName:"Kazuko Kudo",slug:"kazuko-kudo"}]},{id:"43385",title:"Molecular Pathways of Down Syndrome Critical Region Genes",slug:"molecular-pathways-of-down-syndrome-critical-region-genes",signatures:"Ferdinando Di Cunto and Gaia Berto",authors:[{id:"157492",title:"Prof.",name:"Ferdinando",middleName:null,surname:"Di Cunto",fullName:"Ferdinando Di Cunto",slug:"ferdinando-di-cunto"},{id:"158844",title:"Dr.",name:"Gaia",middleName:null,surname:"Berto",fullName:"Gaia Berto",slug:"gaia-berto"}]},{id:"43386",title:"Risk Factors for Down Syndrome Birth: Understanding the Causes from Genetics and Epidemiology",slug:"risk-factors-for-down-syndrome-birth-understanding-the-causes-from-genetics-and-epidemiology",signatures:"Sujay Ghosh and Subrata Kumar Dey",authors:[{id:"31178",title:"Prof.",name:"Subrata",middleName:"Kumar",surname:"Dey",fullName:"Subrata Dey",slug:"subrata-dey"},{id:"125697",title:"Prof.",name:"Sujoy",middleName:null,surname:"Ghosh",fullName:"Sujoy Ghosh",slug:"sujoy-ghosh"}]},{id:"42500",title:"RCAN1 and Its Potential Contribution to the Down Syndrome Phenotype",slug:"rcan1-and-its-potential-contribution-to-the-down-syndrome-phenotype",signatures:"Melanie A. Pritchard and Katherine R. Martin",authors:[{id:"156218",title:"Dr.",name:"Melanie",middleName:null,surname:"Pritchard",fullName:"Melanie Pritchard",slug:"melanie-pritchard"}]},{id:"43392",title:"Laterality Explored: Atypical Hemispheric Dominance in Down Syndrome",slug:"laterality-explored-atypical-hemispheric-dominance-in-down-syndrome",signatures:"George Grouios, Antonia Ypsilanti and Irene Koidou",authors:[{id:"39181",title:"Prof.",name:"George",middleName:null,surname:"Grouios",fullName:"George Grouios",slug:"george-grouios"},{id:"45480",title:"Dr.",name:"Antonia",middleName:null,surname:"Ypsilanti",fullName:"Antonia Ypsilanti",slug:"antonia-ypsilanti"},{id:"162500",title:"Prof.",name:"Irene",middleName:null,surname:"Koidou",fullName:"Irene Koidou",slug:"irene-koidou"}]},{id:"43394",title:"Genetic and Epigenetic Mechanisms in Down Syndrome Brain",slug:"genetic-and-epigenetic-mechanisms-in-down-syndrome-brain",signatures:"Jie Lu and Volney Sheen",authors:[{id:"40911",title:"Dr.",name:"Volney",middleName:null,surname:"Sheen",fullName:"Volney Sheen",slug:"volney-sheen"},{id:"47427",title:"Dr.",name:"Jie",middleName:null,surname:"Lu",fullName:"Jie Lu",slug:"jie-lu"}]}]}]},onlineFirst:{chapter:{type:"chapter",id:"67310",title:"Aluminum Alloys Behavior during Forming",doi:"10.5772/intechopen.86077",slug:"aluminum-alloys-behavior-during-forming",body:'\n
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1. Introduction
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Formability is defined as plastic deformation ability to produce a part with definite requirements on mechanics, dimension, and appearance of a material during a forming process, being mainly limited by the occurrence of flow localization or variability. The formability of any sheet material depends on the material properties, process parameters, and strain bounding criteria. The formability can be evaluated through simulation tests like stretching, deep drawing and drawing processes, mechanical tests, limiting dome height (LDH), and forming limit diagrams at various conditions. Evaluating the formability of aluminum alloys is crucial for industries like aerospace and automotive due to their significant advantages over other materials. Aluminum alloys are majorly categorized as 1xxx, 2xxx, 3xxx, 4xxx, 5xxx, 6xxx, 7xxx, and 8xxx based on major alloying elements. Among all, 2xxx, 5xxx, 6xxx, and 7xxx are having majority of applications in any industry. Forming behavior of aluminum alloys has been evaluated through different processes including deep drawing, stretching, incremental forming, bending, hydroforming, etc., under different process conditions (cold, warm, and hot conditions) and process parameters. Each process has its own process feasibility to evaluate the formability without any forming defects in products. The significance of this chapter is to discuss and elaborate the effect of forming process parameters of different processes on various aluminum alloys. Specifically, the hot forming process, deep drawing process, incremental forming process, tube hydroforming process, and stretching process are discussed on different aluminum alloys.
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2. Aluminum alloy behavior during hot forming
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Hot forming of aluminum alloys is extensively used in the modern industry and has been explored by many researchers and scientists. The main intension to derive this process is to reduce in-flow stress, increase ductility, reduce work hardening, increase toughness of the material, etc. Furthermore, temperatures lower than those involved during hot forging make easier the obtaining of close tolerances and high surface finish [1]. To lead the hot forming process on different aluminum alloys, different process parameters were considered and the attachable results to the literature were derived.
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For details, high-temperature tensile deformation of AA 6082-T4 was experimented in the temperature range of 623–773 K at several strain rates in the range of 5 × 10−5 to 2 × 10−2 s−1. By this, stress exponent n of 7 during the ranges of temperatures and strain rates was tested. This is higher than what is usually observed in Al-Mg alloys under similar experimental conditions. Improvement in the strain exponent of any material leads to better formability [2]. Hot compression tests were performed on aluminum alloys 7150 and 2026 by varying the temperature from 300°C to 450°C and at a strain rate from 0.01 s−1 to 10 s−1 [3, 4]. Also, on AA 7075-T6 and AA 7085 aluminum alloy [5, 6] tested at different temperatures and strain rates (450, 500, 520, 550, 580°C and 0.004, 0.04 and 0.4 s−1 for AA 7075 and AA 7085 in the temperature range from 250°C to 450°C and at strain rate from 0.01 s−1 to 10 s−1 using Gleeble-1500 system, whereas hot deformation behavior was studied on aluminum alloys consisting of Al–6.2Zn–0.70Mg–0.3Mn–0.17Zr with temperature range of 623–773 K and strain rate of 0.01–20 s−1 [7]. Using the metallographic and transmission electron microscope, structural changes were studied. The results showed that the true stress-true strain curves exhibit a peak stress at a critical strain, after which the flow stresses decrease monotonically until high strains. The peak stress level decreases with increasing deformation temperature and decreasing strain rate. Similarly, Ag-containing 2519 aluminum alloy hot deformation behaviors were studied by isothermal compression at 300–500°C with strain rates from 0.01 to 10 s−1. Consequences indicated that by increasing the strain rate and decreasing the deformation temperature, the flow stress of the alloy increased. And also, at a strain rate lower than 10 s−1, the flow stress increases with increasing strain until the stress reached the peak value, and later on, a constant flow stress was noted [8]. Aluminum alloy of grade 7075 sheets fabricated by twin roll casting and deformation behavior was investigated at high temperature. At high temperatures from 350 to 500°C and strain rates from 1 × 10−3 to 1 × 10−2 s−1, hot tensile test was performed. The results showed that by increasing the strain rate and decreasing deformation temperature, flow stress was increased [9]. Similarly, three aluminum alloys containing different silicon contents were studied at a temperature range of 573–773 K with strain rates of 0.01, 0.1, 1 and 5 s−1 [10].
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Hot deformation behavior using processing map technique of stir cast 7075 alloy was studied. Based on the values of a dimensionless parameter like an efficiency index of energy dissipation, mapping was understood in terms of microstructural processes. Under the temperature and strain rate conditions, the processing map exhibited one distinct domain without any unstable flow conditions. In the processing map, the dynamic recrystallization zone and instable zones were identified. The processing maps can be used to select optimum strain rates and temperatures for effective hot deformation of 7075 alloy [11].
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Elevated temperature and strain rate were aimed by stamping of AA5083 sheet components. To evaluate mechanical properties and forming behavior, tensile and Nakajima-type tests were carried out. The material flow stress, ductility, and fracture limit sensitivity to temperature and strain rate were evaluated. And also, the optimal combination of process parameters for maximum formability and effective post-deformation mechanical properties were determined [12]. A special device was developed to investigate the hot forming-quenching integrated process of cold-rolled 6A02 aluminum alloy sheet. The strengthening effect was replicated by hardness and uniaxial tensile tests. Microstructure examination was also conducted to clarify the strengthening mechanism. Results showed that hardness increases with solution time increase, and improves significantly after artificial aging. The faster the cooling rate, the greater the strengthening effect. On the same alloy, hot forming-quenching integrated process at different temperatures from 50 to 350°C was investigated. Results showed that the Vickers hardness and tensile strength decreased with increasing forming-dies temperature. To obtain enough strengthening effect, the forming-dies temperature should not be more than 250°C [13].
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Springback and microstructure of the final products were analyzed and mechanical properties of the material were measured by tensile tests. The results show that HFSC can improve the formability of AA2024 aluminum alloy. After natural aging for 96 h at room temperature, the products were subjected to the hot bending process with synchronous cooling exhibiting a significant increase in strength. Springback of the aluminum alloy AA5754 under hot stamping conditions was characterized under stretch and pure bending conditions. It was found that elevated temperature stamping was beneficial for springback reduction, at hot dies [14, 15]. Hot stamping was developed for aluminum alloy to improve formability and avoid thermal distortion by combining hot forming and quenching. The effects of heating temperature on formability and strengthening of a solution treated with Al-Mg-Si alloy sheet, uniaxial tensile test, deep drawing test, and free bulging test were carried out at temperatures ranging from 25 to 500°C. It was observed that when temperature was raised to 400°C, the fracture strain and limiting bulging height were increased, whereas the limiting drawing ratio increased as temperature elevated to 200°C and declined subsequently. The mechanical property hardness was changed by increasing temperature and at 200 and 500°C, two peak hardness values were noted. Enhanced formability and strength were obtained simultaneously at 200 and 500°C, either of which can be chosen as appropriate forming temperatures for hot stamping [16]. At different solution heat treatment (SHT) temperatures, SHT time and lubricant stamping experiments were performed with 6061 and 7075 aluminum alloy sheets to investigate the formability and lubrication off a B-pillar. After trimming precision level, forming detections were also carried out. From these observations, the B-pillar wrinkled badly and cracked or even broke into pieces in cold stamping with or without lubricants [17].
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For AA 6061 tailor rolled blanks (TRBs), an integrated hot forming and heat treatment process was proposed to improve the formability and dimensional accuracy. The experimentation of this process for sheet forming of Al6061 TRB was evaluated by performing the Erichsen and V-bending tests. The integrated hot forming and heat treatment process was also compared with the conventional forming method in terms of formability, dimensional accuracy, and mechanical properties [18]. A hot AA6082 specimen and cold P20 tools were studied as a function of contact pressure, specimen thickness, and lubricant, using the inverse FE simulation method for the interfacial heat transfer coefficient (IHTC) evolutions. To predict IHTC evolutions with reductions of different lubricants of sliding distance at different contact pressures and sliding speeds as a function, an interactive model was developed. The interaction between the lubricant and IHTC was deducted such that it had three stages such as stage I: the lubricant is applied excessively and the IHTC is plateaued, stage II: in which the lubricant diminishes during sliding and the IHTC decreases, and stage III: lubricant breakdown occurs and the IHTC is equal to its values under dry conditions [19].
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3. Aluminum alloy behavior during deep drawing process
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The drawing of metal or “deep drawing” is the process by which a punch force is applied to sheet metal to flow between the surfaces of a punch die. By this, the sheet is formed into cylindrical, conic, or box-shaped parts. The development of the deep drawing process has paralleled scientific development, particularly in the aircraft and automotive industries. This process is more popular because of its swift press cycle times. Complex axisymmetric geometries and certain nonaxisymmetric geometries can be produced with a few operations. With respect to the functional perspective, the deep drawing process produces high-strength and lightweight parts as well as geometries unattainable with some other manufacturing processes [20]. A schematic illustration of these deep drawing processes is shown in Figure 1. This design is made in such a way that thickness reduction of the workpiece material has been avoided completely (Figure 1). For this process, the basic tools are the punch, the drawing die ring, and the blank holder.
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Figure 1.
Schematic illustration of deep drawing process [20].
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Figure 2 shows the important process parameters involved in the deep drawing process. In addition, material properties such as the strain hardening coefficient (n) and normal anisotropy (R) affect the deep drawing operation.
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Figure 2.
Significant variables in deep drawing [20].
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Instead of tool temperatures, forming temperature curves (FTCs) were characterized from AA5754-O as a workpiece temperature at the warm deep drawing (WDD) process. The distinctive behavior of these curves was examined under nonisothermal WDD of AA 5754-O. The process parameters were considered such as FTC, blank holder force, and punch velocity to assure deep drawability. Optimum conditions were investigated by evaluating the cup volume and springback parameters. In the findings, 330°C in the flange-die radius region and 100°C in the cup wall-punch bottom region were the ideal optimum temperatures for the warm deep drawing process [21]. The stress-strain response of AA2014, AA5052, and AA6082 aluminum alloys at four temperatures: 303, 423, 523 and 623 K, and three strain rates: 0.0022, 0.022, and 0.22 s−1 was evaluated through uniaxial tensile tests. It was found that the Cowper-Symonds model was not a robust constitutive model, and failed to predict the flow behavior. A comparative study was followed for modeling of three aluminum alloys under the mentioned strain rates and temperatures. For comparison, the capability of Johnson-Cook model, modified models of Zerilli-Armstrong and Arrhenius and artificial neural network were considered for constitutive behavior. Better formability of the materials was observed at an elevated temperature of 623 K in terms of cup height and maximum safe strains by conducting cylindrical cup deep drawing experiments under two different punch speeds of 4 and 400 mm/min [22]. Tensile tests of AA5754-H22 aluminum alloy were carried out at five different temperatures and three different strain rates to investigate the deformation behavior correlating with the Cowper-Symonds constitutive equation.
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When punch and die were heated to 200°C, the forming limit strain and dome height were improved. Significant enhancement was noted when the die and punch temperatures were maintained at 200 and 30°C, respectively, in deep drawn cup depth. Using a thermo-mechanical FE model, the forming behavior at different isothermal and nonisothermal conditions was predicted. In the FE model, temperature-dependent properties in Barlat-89 yield criterion and coupled with Cowper-Symonds hardening model were used. The validation had taken place using thinning/failure location in deformed cups by implementing the experimental limiting strains as damage model [23].
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Deep drawing of aluminum alloy AA6111 at elevated temperatures was analyzed with the effect of friction coefficient through experiments and finite element method. Results indicated that the friction coefficient and lubrication position influence the minimum thickness, the thickness deviation, and the failure mode of the formed parts. During the hot forming process, the failure modes were draw mode, stretch mode, and equi-biaxial stretch mode. Fracture occurred at the center of cup bottom or near the cup corner in a ductile mode or ductile brittle mixed mode [24]. Simulations of deep drawing tests at elevated temperatures were carried out with experimental validation on aluminum alloy 7075. For stamping operations, some of the important parameters such as blank holder force, stamping speed, blank temperature, and friction coefficient were considered. During the experimentation, stamping tests were performed at temperature between 350 and 500°C, 0 and 10 kN blank holding force, 50 and 150 mm/s stamping speed, and 0.1 and 0.3 frictional coefficient. At lower values of temperature, blank holder force and friction coefficient improvement were seen in thickness homogeneity whereas formability was improved with the well lubricated blank at about 400°C temperature and stamping speed 50 mm s−1 [25]. Tailor friction stir welded blanks (TFSWBs) of AA5754-H22 and AA5052-H32 sheet metals were fabricated using a tool with optimized design along with optimized process parameters. For optimization to design the friction stir welding experiments, Taguchi L9 orthogonal array was used. For the multi-objective optimization to maximize the weld strength and total elongation reducing the surface roughness and energy consumption, the gray relational analysis was applied. The formability was evaluated and compared with TFSWBs and parent materials using LDR tests. The analysis had proved that TFSWBs were comparable with parent materials more specifically without any failure in the weld zone area. For improvement in the LRD, a modified conical tractrix die was proposed and 27% improvement was observed.
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Simulations of cylindrical cup drawing were carried out with experimental validation on AA6111 aluminum alloy at elevated temperatures. The influence of four important process parameters, namely, punch velocity, blank holder force (BHF), friction coefficient, and initial forming temperature of blank on drawing characteristics was investigated using design of experiments (DOE), analysis of variance (ANOVA), and analysis of mean (ANOM). Based on the results of ANOVA, the BHF had the greatest influence on minimum thickness. The significance of punch velocity for thickness deviation, BHF, friction coefficient, and initial forming temperature of blank was 44.35, 24.88, 15.77, and 14.995% respectively. Further, the effect of each factor on forming characteristics was analyzed by ANOM [26].
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A design optimization problem was constructed to identify the formability window, in which the punch stroke was maximized subject to wrinkling and tearing. For this, the formability window of a difficult-to-draw material AA 5402 was explained with the pulsating blank holder force (PBHF) and the variable blank holder force (VBHF). Some parameters in the VBHF and PBHF were included and taken as the design variables. A sequential approximate optimization (SAO) using a radial basis function (RBF) network was used to determine the optimal parameter of PBHF and VBHF. From numerical simulation coupled with the SAO using the RBF network using the PBHF and VBHF, formability window was observed. It was identified that the proposed approach was highly useful for clarifying the formability window of a difficult-to-draw material [27]. The tailored heat treated blank (THTB) technique was demonstrated to create a material property gradient through a suitable artificial aging treatment carried out prior to the forming process on the effectiveness of combining the hydromechanical deep-drawing process. This method was coupled with a simple finite element model and a multi-objective optimization platform. For determining the effect of the aging treatment on the mechanical and deformative behavior of the AC170PX aluminum alloy, a preliminary experimental campaign was carried out. The adoption of aged blanks in the hydromechanical deep drawing allows to increase the limit drawing ratio and to simplify the process proved from the optimization results [28].
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For increasing the drawability of AA1200 aluminum alloy cylindrical cups, one technique was developed. For optimal process design, effects of die and punch along with fillet radius of die and punch on LDR, drawing load with respect to punch stroke and strain of the cup wall was investigated numerically. To determine the optimum LDR form numerical analysis, a commercial finite element simulation package, ANSYS 14.0, was used. The effects of the original blank on the various LDR and punch load were numerically investigated. This process successfully produced cylindrical cups with considerable drawing ratio [29]. The effect of pulsating blankholder system was investigated on improving the formability of aluminum 1050 alloy. Using ABAQUS6.7 software, the deep drawing process was simulated for cylindrical cup of AA 1050. Later on, experimental and numerical analyses were compared for depth of cup, tearing, and thickness distribution. The results indicated that with proper frequency and gap, the cup depth and thickness distribution can be improved by using the pulsating blankholder system. Further, good agreement was observed between simulation and experimental results [30]. An analytical model was proposed for the nonuniform fluid pressure distribution in the cavity and for the hydrodynamic flow of the fluid film between the blank and die for AA5086 aluminum alloy. From Reynolds equation solution, the hydrodynamic flow was calculated and model was implemented in ABAQUS/Explicit, finite element software. The approach was validated and investigated for the influences of the blank holder force and the fluid pressure on the formability of the blank metal. The results exhibited that the choice of an appropriate blank holder force reduced the strain in the blank and prevented the risk of fracture [31]. A study was made on deep drawing of SiCp/2024Al composite sheets by considering the effect of pulse current on heating performance and thermal. The high-intensity pulse current flows through the sheet and generates the tremendous Joule heat. The specimen temperature was kept around 673 K at a rate of 13.5 K/s under the current density of 21.7 A/mm2. The temperature difference was reduced by 73.3% by inserting the stainless-steel inserts. Besides, the SiCp/2024Al composite was successfully deep drawn with good surface quality [32]. Deep drawing process characteristics of AA 6xxx alloy sheet were discussed under different process parameters such as punch force, lubrication, fillet radius, punch speed etc., and the formability was evaluated [33, 34, 35, 36, 37].
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4. Aluminum alloy behavior during incremental forming
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Incremental sheet forming (ISF) is a flexible process in which a sheet of metal is formed by a progression of localized deformation. This process does not require any specialized tool; a simple tool moves over the surface of the sheet metal by which localized plastic deformation is initiated. Hence, many shapes can be formed by designing a proper path to a tool. The main motto of this process is to form a sheet metal without any manufacturing of specialized dies [38]. Figure 3 shows an example of the incremental forming. In this Figure 3, according to computer numerical control (CNC) machine program instructions, the ball tool moves on the sheet to form the required shape. Hence, the process is in CNC machine; the program can be edited as per the requirement. From the shown Figure 3, the hollow and square in cross section will be formed [39].
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Figure 3.
Incremental forming of an aluminum sheet on CNC milling machine [34].
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A few observations are made and discussed on incremental forming process. Incremental forming behavior of 6111-T4 an alloy was investigated for exterior body panel applications. Tensile testing data were used to simulate the incremental forming process. The heat treat regimen developed for uniaxial testing was then applied to a series of plane strain tests using a hemispherical punch [40]. The formability of AA-2024 sheets was investigated in the single-point incremental forming (SPIF) process. The process parameters, specifically step size, tool radius, and forming speed, of the SPIF process were varied over wide ranges. The formability was quantified through a response surface method. It was found that the interaction of step size and tool radius was very significant on the formability. The formability of pre-aged AA-2024 sheet decreases with the increase in the forming speed. Additionally, the annealed sheet shows higher formability than the pre-aged sheet [41].
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AA7075-O aluminum alloy sheet forming was investigated using experimental campaign and the forming process mechanism was understood. Tensile tests were carried out to characterize the mechanical properties with three different thicknesses. To illuminate the formability of AA7075-O aluminum alloy sheet, the effects of tool path with different incremental steps and the part height were evaluated. To understand the design limits for strain, a fracture forming limit diagram was developed. The influence of different draw angles, sheet thicknesses, step-down sizes, and sheet orientations was considered to analyze forming forces. The part draw angle and incremental steps of the tool path were more effectible on the formability as concluded from the experimental results. The influences of process parameters on tool forces provide further insights into the deformation mechanics of AA7075-O sheets [42]. The formability of AA5052 aluminum alloy at room temperature was studied through truncated square pyramid and cone formed using a CNC machine. For both the shapes, the forming limit diagram (FLD) and thickness distribution were predicted and compared. The FLD obtained through this process and conventional FLD were different. Comparison of FLD and thickness distribution showed that cone had higher forming limit than square cup and the thickness after forming was better in cone shapes than in square cups [43]. An investigation was made on the deformation characteristic of embossed aluminum sheet in the incremental sheet forming process in which the surface quality of tool path along outward and inward movement was compared and noted as surface quality is better in the outward movement. Using ABAQUS software, a finite element simulation, the experimental results and detailed forming mechanism of the 3D structured sheet were reviewed [44].
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Formability of friction welded blank made of aluminum 6061 was studied experimentally. Formability was evaluated through FLD, dome height, minimum thickness, and thickness distribution. Many experiments were conducted to know which joining direction caused higher formability and desired forming limit curve. Joints were prepared in three different rollings (0, 45, and 90°) and tested for formability test and compared with FLD, dome height, minimum thickness, and thickness distribution. From the formability comparison, the best joining direction was identified. Using the response surface methodology, the effect of welding process parameters such as rotational speed, plunge depth, and travel speed on formability of welded blanks was analyzed. After finding the effects, welded blanks with optimal parameter combination were fabricated and the effect of incremental forming parameters, that is, spindle speed, feeding rate, and axial step on thickness distribution was analyzed. From the results, it was obtained that joints with diagonal direction caused higher value of bowl height [45]. The effect of longitudinal ultrasonic vibrations on the performance of the incremental forming process of aluminum-1050 sheet was studied. In this technique, ultrasonic vibrations with high frequency and low amplitude were axially added to the movement of forming tool. This system is arranged with different parts including a mechanism attached into the chuck of CNC machine and ultrasonic power to the vibratory tool. Parameters like forming force and sheet formability were examined through straight groove test in both conventional and ultrasonic-assisted incremental forming process. The results showed that formability increased and forming force decreased with ultrasonic assistance [46].
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Using the finite element method, the behavior of the state of stresses and strains in the hot incremental sheet forming of 1050 aluminum alloy was evaluated, with and without pre-heating. With the assistance of RADIOSS software, numerical simulation was performed. The results were presented a deterioration in the force during electric hot incremental sheet forming compared to the electric hot incremental sheet forming [47].
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The formability of the AA2024-O aluminum alloy sheet material was evaluated with respect to the impact of forming tool shape, tool diameter, wall angle, step size, sheet thickness, and tool rotation. Forming depth was measured by scanning the components using a noncontact 3D scanner. Wall angle and step size had proved more significant factors which affect the formability greatly [48]. An attempt was made to optimize the incremental forming parameters (spindle speed, tool feed, and step size) for surface roughness to be least and wall thickness to be larger using the response surface method.
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The formability of AA5052 alloy sheets at room temperature was checked with pre-cut holes at the center with different diameters. In the forming operation, cone-shaped parts were formed with the optimized values. Formability was compared with sheet with smaller holes and larger holes and it was observed that smaller holes had better formability. Also, the thickness of the formed part wall without hole is less. As the diameter of the hole increases, the wall thickness also increases [49].
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To evaluate deformation behavior of AA-6061 aluminum alloy sheet, the single point incremental forming (SPIF) process was chosen. To form the sheet into the desired conical shape, the SPIF experiments and finite element method simulation were performed and to measure the major and minor strains, the digital image correlation (DIC) method was used. The major and minor strains in post deformation results were compared with FEM results for AA6061 thin sheet material. An experimental fracture forming limit diagram was assessed using the punch stretching test.
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Consequently, the effective plastic strains at the onset of fracture were predicted and compared with experimental data. In order to get insight into forming behavior and surface roughness, the microstructural examination on the truncated dome fabricated using optimized parameters was carried out through micro-texture analyses [50]. By using the electric hot incremental forming process (EHIF), the dimensional accuracy of parts has got more improvement compared to single-stage forming and double-stage forming at room temperature. The effect of EHIF process parameters, such as tool diameter, feed rate, step size, and current, on temperature was studied. For a cone of AA 1060, the maximum temperature, the average temperature, and the maximum temperature difference were measured. Besides, the response surface method and Box–Behnken design were employed, and they established corresponding models to predict targeted values [51].
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AA 7075-O sheets were formed into variable angle funnels and 45° wall angle cones by SPIF. The same material was deep drawn and a bulge test part was formed to compare with SPIF. Moreover, the formed parts were sectioned and characterized for texture and surface finish at equivalent strains. To compare the strain paths of SPIF and deep drawing, finite element models were used [52]. For AA 1050 sheet metal, the deformation characteristics, forming behavior, and deformation mechanism of the SPIF process were evaluated. For process deformation characteristics such as dimensional accuracy, thickness distribution, true surface strain, von Mises stress, and equivalent plastic strain, evolved at different forming stages, were estimated through experimental investigation and finite element analysis. Analysis was carried out to identify the reason of typical failure under biaxial strain mode [53].
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5. Aluminum alloy behavior during hydroforming process
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The metal forming process in which a pressurized fluid either plastically deforms or aids in deforming a given blank material (sheet or tube) into a desired shape as depicted is a hydroforming process. Figure 4 indicates the complete process. Using this process, more complex shapes with more strength and low cost can be manufactured as compared with stamping, forging, or casting processes [54].
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Figure 4.
Steps in a typical hydroforming process shown on a small tubular part [54].
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Tube hydroforming process on different aluminum alloys is discussed in the following sections. At different temperatures, tube hydroforming analysis of aluminum alloy AA1050 was studied and the effect of temperature on thickness distribution of the final product was investigated. Also, for evaluating numerical results, a warm hydroforming set-up had been designed and manufactured. Conferring to numerical and experimental results in the case of free bulging, increase of the process temperature causes more uniform thickness distribution which leads to better material formability. A viscoplastic model was developed to consider the influence of microscopic evolution and macroscopic deformation to represent the deformation behavior of aluminum alloy sheet AA7075-O in the warm hydroforming process. By using the pressure rate, the evolution of dislocation density and kinematic isotropic hardening on a hydroforming environment, a set of rate dependent constitutive equations was constructed and proposed to predict stress-strain response of the material. The hydraulic bulge experiments on aluminum alloy at warm temperature indicated that the deformation behavior of the material was more sensitive to pressure rate. To determine the optimum values of a set of free material constants associated with the proposed constitutive model, the genetic algorithm optimization technique was used. The computed data were in good agreement with the test data on the basis of the optimized material constants [55, 56].
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Friction stir welding (FSW) tube of 2024-O aluminum alloy rolled plates was coiled and produced by processing sequence. The plastic deformation characteristics were investigated experimentally and numerically during hydroforming with two types of end conditions. The performance of the FSW tubes was investigated by die-bulge forming with fixed ends. The wrinkling behavior during hydroforming was analyzed by employing axial feed on the tube ends. Severe thinning was observed at one quarter of the expansion zone from symmetry plane. Along the hoop direction, the base material near the weld observed a severe thinning. The thickness distribution greatly depends on the sequence of the contacting die and the variations of the curvature radius of the tube during hydroforming. Moreover, the weld shows an inhibitory effect for the generation of the wrinkles and decreases the number of the wrinkles as compared to the seamless tube during hydroforming [57].
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An experimental and numerical simulation was studied on 6063-T4 aluminum alloy cross member through the hydroforming process. Severe thinning and bursting were avoided during hydroforming, composite design method was carried out, and the significance of pre-form structural parameters was discussed on thinning. An experimental research was conducted on thickness distribution of typical sectional profiles and dimension accuracy as per the optimum pre-form shape.
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FEM simulations and experiments were conducted on the formability of aluminum alloy AA2024-O. The effects of strain rate on the formability during the active hydroforming process were investigated. Results indicated that aluminum alloy AA2024-O is not sensitive to pressure rate at room temperature. Furthermore, the deformation capacity of aluminum alloys can be improved effectively, and more uniform distribution of wall thickness can be obtained. The wrinkling behavior and thickness distribution of 5A06 aluminum alloy sheets in an annealed state was investigated numerically and experimentally under different hydraulic pressures in the hydroforming of single-layer and double-layer sheets. The upper, thicker sheet synchronously deforms with the lower, thinner sheet during hydroforming. When the double-layer sheets were separated, a thinner curved sheet part will be manufactured. From the simulation and experimental results, the upper, thicker sheet was effectively suppressing the wrinkles of the lower, thinner sheet and improved the thickness distribution. This was due to the increasing anti-wrinkle ability of the formed sheet and the interfacial friction between the double-layer sheets. In addition, the maximum hydraulic pressure was decreased via hydroforming of double-layer sheets. This method reduced the drawing force for large sheet parts and meets the requirement of energy conservation [58, 59, 60].
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A specialized hydroforming process set-up was designed for 2A12 aluminum alloy curved shell double-sided sheet. The influence of double-sided liquid pressure on the thickness distribution was evaluated. The thickness distribution of the formed shells was measured and compared under different loading paths. Using simulation analysis, the deformation mode and the stress state were analyzed to understand the mechanism of the thickness variation. It was shown that the forward pressure plays a negative role in the thickness distribution of the formed parts. The deformation mode of the shells varies slightly when forward pressures are added. The Von Mises stress and the effective strain of the components were improved when conducting the double-sided hydroforming process. The larger thinning phenomenon was noted by adding forward pressure and by increasing reduced third principle stress on the blank. Through a steam hydroforming process, an experimental formability study was carried out on aluminum sheet 2017A. The steam hydroforming process takes advantage of the coupling between the thermal and mechanical loads applied. The variation of the supplied electrical power on the hydroforming temperature and steam pressure effects was studied. The evolution of strains and stresses in metal sheets was analyzed. The experimental results showed that the supplied electrical power increases the heating rate and has no effect on bursting temperature or pressure. Furthermore, the evolution of the vapor pressure as a function of temperature was independent of the supplied electrical power and the deformation in the thin sheets under the steam pressure decreases the stress flow and raises the plastic deformation [61, 62].
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Using elliptical bulging dies under various temperatures and pressure rates, warm/hot sheet bulging tests were conducted on 2A16-O aluminum alloy. The macroscopic and microscopic influence of the pressure rate on the formability and microstructural evolution of hydrobulging parts during warm/hot sheet hydroforming was investigated. The results revealed that the forming limit of the aluminum alloy was influenced by the pressure rate as the temperature rose, wherein a lower pressure rate resulted in a higher forming limit. This study demonstrated that warm/hot sheet hydroforming of aluminum alloy may lead to an improved forming limit and inhibit microstructural degradation during processing [63]. A hydroforming analysis was made on extruded aluminum tubular specimen made up of AA 6063 alloy bulged from the diameter of 38–54 mm. The thickness distribution at bulging the region along lateral and longitudinal directions was analyzed. The parameters considered are axial feed, tube thickness, fluid pressure, and die semi-cone angle. The forming characteristics such as thickness distribution and bulged diameter were studied using toolmaker microscope and coordinate measuring machine. Maximum shear thinning is observed in the largest diameter of the bulged portion of the tube [64].
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6. Aluminum alloy behavior during bi-axial forming
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Here, some of the recent discussions are made based on the bi-axial forming process. It is also treated as a stretching process in which sheet material experiences the tensile load along plane direction in the same time.
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Biaxial warm forming behavior in the temperature range 200–350°C was investigated for three aluminum sheet alloys: Al 5754, Al 5182, and Al 6111-T4. The formability for all the three alloys improved at elevated temperatures; the strain hardened alloys Al 5754 and Al 5182 showed considerably greater improvement than the precipitation hardened alloy Al 6111-T4. Formability was studied by forming rectangular parts at a rapid rate using internally heated punch and die in both isothermal and nonisothermal conditions. The temperature effect on drawing of the sheet was found to have a large effect on formability. FLD under warm forming conditions was also determined, which showed results that are consistent with the evaluation of part depth. Biaxial forming behavior was investigated for three aluminum sheet alloys of Al 5182, Al 5754, and 6111-T4 using a heated die and punch in the warm forming temperature range of 200–350°C. It was found that all three alloys exhibited significant improvement in the formability compared with that at room temperature. The nonheat-treatable alloys of AA 5182 and AA 5754 showed a higher part depth than that of heat-treatable 6111-T4. The formidability characteristic was dependent on the blank holding pressure (BHP). When the BHP decreased, the formability increased, but increasing the forming temperature and/or BHP minimizes the wrinkling tendency and improves the forming performance. By increasing temperature and BHP, the stretchability of the sheet alloys was increased. Through setting the temperature 50°C higher than the punch temperature to enhance the drawing component, the optimum formability was achieved. Strain distribution was also improved with setting the die temperature higher than the punch temperature in a part in such a manner that postpones necking and fracture by altering the location of the greatest thinning [65].
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The Gurson-Tvergaard-Needleman (GTN) damage model combined with the finite element method was used to investigate the influence of double-sided pressure on the deformation behavior of biaxially stretched AA6111-T4 sheet metal. The Marciniak-Kuczynski (M-K) localized necking model was used to predict the right-hand side of the forming limit diagram (FLD) of sheet metal under superimposed double-sided pressure. The forming limit curve (FLC) of the biaxially stretched AA6111-T4 sheet metal under the superimposed double-sided pressure had improved and the fracture locus shifts to the left. Besides, the formability increase value is sensitive to the strain path [66].
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Through the numerical biaxial tensile tests of the sheet, the biaxial tensile deformation behavior of 5182 aluminum alloy sheet was predicted. From the numerical simulations, the stress-strain curves and the shapes of the contours of plastic work were calculated and were quantitatively verified by the experimental biaxial tensile test using the cruciform specimen. Using the results of experimental and numerical biaxial tensile tests, parameters of the Yld2000-2d yield function were identified. Von Mises’s and Hill’s yield functions were identified using the experimental data and were compared. The simulation results confirmed that the forming simulation using the Yld2000-2d yield function identified by the numerical biaxial tensile tests was better than that of the Mises’s and Hill’s yield functions and was comparable to that of the Yld2000-2d yield function calibrated experimentally [67].
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The forming limit strains at fracture for aluminum alloy 5086 were determined using an in-plane biaxial tensile test with a cruciform specimen. To identify the onset of fracture and the forming limit strains, a method based on the evolution of strain in the central area of the specimen and the observation of the macroscopic image of specimen surface was proposed. The forming limit strains at fracture were determined under different strain paths provided by the two independent axes of the experimental device. Finite element simulations were performed to determine and compare numerical forming limit strains with three ductile fracture criteria [68]. Warm temperature biaxial tension test apparatus was developed to achieve stress ratio and strain rate controls simultaneously. The warm temperature biaxial tension tests were conducted on AA5182-O aluminum alloy sheet with the thickness of 1 mm. The obtained results showed that the shapes of equi-plastic work loci did not have strong temperature dependency [69].
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7. Summary
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Forming behavior of different aluminum alloys is discussed in the above sections. The forming processes considered included the hot forming process, deep drawing process, incremental process, hydroforming process, and bi-axial forming. The effect of their parameters on aluminum alloys is realized. From each forming process and test, the forming limit strain is determined to quantify the formidability of each aluminum alloy. Moreover, the quantification of the formability of Al alloys can help the industries.
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\n\n',keywords:"ISF, hot forming, tube hydroforming, deep drawing, stretching",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/67310.pdf",chapterXML:"https://mts.intechopen.com/source/xml/67310.xml",downloadPdfUrl:"/chapter/pdf-download/67310",previewPdfUrl:"/chapter/pdf-preview/67310",totalDownloads:370,totalViews:0,totalCrossrefCites:0,dateSubmitted:"November 5th 2018",dateReviewed:"March 27th 2019",datePrePublished:"November 27th 2019",datePublished:"March 4th 2020",dateFinished:null,readingETA:"0",abstract:"Industrial revolution toward weight reduction and fuel efficiency of the automotive and aerospace vehicles is the major concern to replace heavy metals with light weight metals without affecting much strength. For this, aluminum alloys are the major contributors to those industries. Moreover, aluminum alloys are majorly categorized as 1xxx, 2xxx, 3xxx, 4xxx, 5xxx, 6xxx, 7xxx, and 8xxx based on major alloying elements. Among all, 2xxx, 5xxx, 6xxx, and 7xxx are having majority of applications in the abovementioned industries. For manufacturing any engineering deformable components, forming characteristics are must. Forming behavior of aluminum alloys has been evaluated through different processes including deep drawing, stretching, incremental forming, bending, hydro forming etc., under different process conditions (cold, warm, and hot conditions) and process parameters. Each process has its own process feasibility to evaluate the formability without any forming defects in products. The present chapter discusses a few important processes and their parameter effect on the aluminum alloys through the experimentations and simulation works.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/67310",risUrl:"/chapter/ris/67310",signatures:"Perumalla Janaki Ramulu",book:{id:"8862",title:"Aluminium Alloys and Composites",subtitle:null,fullTitle:"Aluminium Alloys and Composites",slug:"aluminium-alloys-and-composites",publishedDate:"March 4th 2020",bookSignature:"Kavian Omar Cooke",coverURL:"https://cdn.intechopen.com/books/images_new/8862.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"138778",title:"Dr.",name:"Kavian",middleName:"Omar",surname:"Cooke",slug:"kavian-cooke",fullName:"Kavian Cooke"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"283483",title:"Associate Prof.",name:"Perumalla",middleName:null,surname:"Janaki Ramulu",fullName:"Perumalla Janaki Ramulu",slug:"perumalla-janaki-ramulu",email:"perumalla.janaki@astu.edu.et",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Aluminum alloy behavior during hot forming",level:"1"},{id:"sec_3",title:"3. Aluminum alloy behavior during deep drawing process",level:"1"},{id:"sec_4",title:"4. Aluminum alloy behavior during incremental forming",level:"1"},{id:"sec_5",title:"5. Aluminum alloy behavior during hydroforming process",level:"1"},{id:"sec_6",title:"6. Aluminum alloy behavior during bi-axial forming",level:"1"},{id:"sec_7",title:"7. Summary",level:"1"}],chapterReferences:[{id:"B1",body:'Cavaliere P. Hot and warm forming of 2618 aluminium alloy. Journal of Light Metals. 2002;2(4):247-252. DOI: 10.1016/S1471-5317(03)00008-7\n'},{id:"B2",body:'El-Danaf EA, AlMajid AA, Soliman MS. Hot deformation of AA6082-T4 aluminum alloy. Journal of Materials Science. 2008;43(18):6324. DOI: 10.1007/s10853-008-2895-4\n'},{id:"B3",body:'Jin N, Zhang H, Han Y, Wu W, Chen J. Hot deformation behavior of 7150 aluminum alloy during compression at elevated temperature. 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Numerical investigation and optimization of pulsating and variable blank holder force for identification of formability window for deep drawing of cylindrical cup. The International Journal of Advanced Manufacturing Technology. 2016;82(1-4):583-593. DOI: 10.1007/s00170-015-7385-7\n'},{id:"B28",body:'Piccininni A, Di Michele G, Palumbo G, Sorgente D, Tricarico L. Improving the hydromechanical deep-drawing process using aluminum tailored heat treated blanks. Acta Metallurgica Sinica. 2015;28(12):1482-1489. DOI: 10.1007/s40195-015-0347-0\n'},{id:"B29",body:'Dwivedi R, Agnihotri G. Numerical simulation and experimental analysis on the deep drawing of cylindrical cups. Transactions of the Indian Institute of Metals. 2015;68(1):31-34. DOI: 10.1007/s12666-015-0598-5\n'},{id:"B30",body:'Liu ZY, Xiong BQ , Li XW, Yan LZ, Li ZH, Zhang YA, et al. Deep drawing of 6A16 aluminum alloy for automobile body with various blank-holder forces. Rare Metals. 2018;37:1-8. DOI: 10.1007/s12598-018-1146-3\n'},{id:"B31",body:'Abbadeni M, Zidane I, Zahloul H, Fatu A, Hajjam M. Finite element analysis of fluid-structure interaction in the hydromechanical deep drawing process. Journal of Mechanical Science and Technology. 2017;31(11):5485-5491. DOI: 10.1007/s12206-017-1043-y\n'},{id:"B32",body:'Wang B, Wang GF, Jiang SS, Zhang KF. Effect of pulse current on thermal performance and deep drawing of SiCp/2024Al composite sheet. The International Journal of Advanced Manufacturing Technology. 2013;67(1-4):623-627. DOI: 10.1007/s00170-012-4510-8\n'},{id:"B33",body:'Pranavi U, Reddy PV, Lavanya K, Charyulu NN, Ramulu PJ. Effect of mechanical properties on deep drawing formability prediction. International Journal of Current Engineering and Technology. 2014;2:303-305. DOI: 10.14741/ijcet/spl.2.2014.5\n'},{id:"B34",body:'Pranavi U, Ramulu PJ, Chandramouli C, Govardhan D, Prasad PR. Formability analysis of aluminum alloys through deep drawing process. 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DOI: 10.1007/s12666-017-1093-y\n'},{id:"B46",body:'Amini S, Gollo AH, Paktinat H. An investigation of conventional and ultrasonic-assisted incremental forming of annealed AA1050 sheet. The International Journal of Advanced Manufacturing Technology. 2017;90(5-8):1569-1578. DOI: 10.1007/s00170-016-9458-7\n'},{id:"B47",body:'Pacheco PA, Silveira ME. Numerical simulation of electric hot incremental sheet forming of 1050 aluminum with and without preheating. The International Journal of Advanced Manufacturing Technology. 2018;94(9-12):3097-3108. DOI: 10.1007/s00170-017-0879-8\n'},{id:"B48",body:'Kumar A, Gulati V, Kumar P, Singh V, Kumar B, Singh H. Parametric effects on formability of AA2024-O aluminum alloy sheets in single point incremental forming. Journal of Materials Research and Technology. 2018;8(1):1461-1469. DOI: 10.1016/j.jmrt.2018.11.001\n'},{id:"B49",body:'Mugendiran V, Gnanavelbabu A. Analysis of hole flanging on AA5052 alloy by single point incremental forming process. 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Microstructure and texture-based analysis of forming behavior and deformation mechanism of AA1050 sheet during single point incremental forming. Journal of Materials Processing Technology. 2019;266:292-310. DOI: 10.1016/j.jmatprotec.2018.11.012\n'},{id:"B54",body:'Koç M, editor. Hydroforming for Advanced Manufacturing. Woodhead Publishing; 2008. https://www.elsevier.com/books/hydroforming-for-advanced-manufacturing/koc/978-1-84569-328-2\n\n'},{id:"B55",body:'Hashemi SJ, Naeini HM, Liaghat G, Tafti RA, Rahmani F. Numerical and experimental investigation of temperature effect on thickness distribution in warm hydroforming of aluminum tubes. Journal of Materials Engineering and Performance. 2013;22(1):57-63. DOI: 10.1007/s11665-012-0213-4\n'},{id:"B56",body:'Lang L, Du P, Liu B, Cai G, Liu K. Pressure rate controlled unified constitutive equations based on microstructure evolution for warm hydroforming. Journal of Alloys and Compounds. 2013;574:41-48. DOI: 10.1016/j.jallcom.2013.03.134\n'},{id:"B57",body:'Hu ZL, Wang XS, Pang Q , Huang F, Qin XP, Yuan SJ, et al. Experimental and numerical study on hydroforming characteristics of friction stir welded aluminum alloy tubes. The International Journal of Advanced Manufacturing Technology. 2015;80(5-8):959-969. DOI: 10.1007/s00170-014-6613-x\n'},{id:"B58",body:'Kong D, Lang L, Sun Z, Ruan S, Gu S. A technology to improve the formability of thin-walled aluminum alloy corrugated sheet components using hydroforming. The International Journal of Advanced Manufacturing Technology. 2016;84(1-4):737-748. DOI: 10.1007/s00170-015-7727-5\n'},{id:"B59",body:'Zhou BJ, Xu YC. Wrinkle behavior of hydroforming of aluminum alloy double-layer sheets. Journal of Metals. 2016;68(12):3201-3207. DOI: 10.1007/s11837-016-2025-8\n'},{id:"B60",body:'Cai Y, Wang XS, Yuan SJ. Pre-form design for hydro-forming of aluminum alloy automotive cross members. The International Journal of Advanced Manufacturing Technology. 2016;86(1-4):463-473. DOI: 10.1007/s00170-015-8160-5\n'},{id:"B61",body:'Liu W, Chen YZ, Yuan SJ. Mechanism analysis on thickness distribution of aluminum alloy hemispherical shells in double-sided sheet hydroforming. The International Journal of Advanced Manufacturing Technology. 2017;89(5-8):2011-2020. DOI: 10.1007/s00170-016-9248-2\n'},{id:"B62",body:'Aissa S, Mohamed S, Tarek L. Experimental study of steam hydroforming of aluminum sheet metal. Experimental Techniques. 2017;41(5):525-533. DOI: 10.1007/s40799-017-0191-4\n'},{id:"B63",body:'Cai G, Wu C, Gao Z, Lang L, Alexandrov S. Investigation on the effect of pressure rate on formability of aluminum alloy during warm/hot sheet hydroforming. AIP Advances. 2018;8(9):095313. DOI: 10.1063/1.5050222\n'},{id:"B64",body:'Selvakumar AS, Rajan BS, Balaji MS, Selvaraj B. Strain analysis of AA6063 aluminum alloy by tube hydroforming process. In: Advances in Manufacturing Processes. Singapore: Springer; 2019. pp. 13-21. DOI: 10.1007/978-981-13-1724-8_2\n'},{id:"B65",body:'Li D, Ghosh AK. Effects of temperature and blank holding force on biaxial forming behavior of aluminum sheet alloys. Journal of Materials Engineering and Performance. 2004;13(3):348-360. DOI: 10.1361/10599490419225\n'},{id:"B66",body:'Liu J, Wang Z, Meng Q. Numerical investigations on the influence of superimposed double-sided pressure on the formability of biaxially stretched AA6111-T4 sheet metal. Journal of Materials Engineering and Performance. 2012;21(4):429-436. DOI: 10.1007/s11665-011-9941-0\n'},{id:"B67",body:'Yamanaka A, Hashimoto K, Kawaguchi J, Sakurai T, Kuwabara T. Material modeling and forming simulation of 5182 aluminum alloy sheet using numerical biaxial tensile test based on homogenized crystal plasticity finite element method. Journal of Japan Institute of Light Metals. 2015;65:561-567\n'},{id:"B68",body:'Song X, Leotoing L, Guines D, Ragneau E. Investigation of the forming limit strains at fracture of AA5086 sheets using an in-plane biaxial tensile test. Engineering Fracture Mechanics. 2016;163:130-140. DOI: 10.1016/j.engfracmech.2016.07.007\n'},{id:"B69",body:'Hamasaki H, Tamashiro F. Biaxial deformation on AA5182-O aluminium alloy sheet at warm temperature. Journal of Physics: Conference Series. 2018;1063(1):012032. DOI: 10.1088/1742-6596/1063/1/012032\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Perumalla Janaki Ramulu",address:"perumalla.janaki@astu.edu.et",affiliation:'
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Crossref
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iThenticate
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Enago
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SPi Global
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Amazon
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DHL
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