Search

Many Mediterranean steepland rivers are flanked by extensive alluvial and colluvial deposits, but Late Quaternary histories of channel and hillslope behaviour remain poorly constrained, primarily because of the limited availability of material suitable for dating. Study of a 4.8 km long reach of the Anapodaris Gorge, located in the lower part of an � 500 km 2 catchment in south central Crete, reveals a succession of well preserved, coarse-grained (predominantly cobble to boulder) and fine-grained (predominantly silt to sand) alluvial deposits that locally interfinger with, or are overlain by, coarse colluvial and tributary stream deposits. Detailed ground surveys, geomorphological mapping, sedimentological investigations, and geochronology (optically stimulated luminescence, radiocarbon, and lichenometry) have allowed detailed reconstruction of the timing and pattern of sedimentation and erosion over the mid to late Holocene. Widespread, coarse-grained aggradational episodes at c. 4.86-4.20 and c. 3.40-3.00 ka have been punctuated by incisional episodes and coarse sediment export, resulting in a suite of alluvial terraces. Comparison with other proxy Mediterranean environmental change records, particularly high-resolution marine and lake records, suggests that these aggradational/incisional episodes were primarily climatically driven, reflecting changes in the balance between hillslope/tributary sediment supply and high-energy flood events. By contrast, phases of widespread fine-grained aggradation at c. 1.90 ka, 1.13 to 1.10 ka, 0.85 to 0.70 ka and 0.21 ka provide evidence for decreases in flood competence, possibly coupled with up-catchment historical land use changes. Since the middle of the nineteenth century, several large floods have formed localised boulder berms and splays and have contributed to stripping of the fine-grained deposits from many parts of the gorge. The findings from the Anapodaris Gorge demonstrate the sensitivity of Mediterranean steepland catchments to rapid and/or short-lived Holocene climate change but also highlight the need for higher resolution data on historical and prehistoric land use changes. © 2009 Elsevier B.V. All rights reserved.

Objective To study PAPP-A and SP1 for biochemical trisomy screening in twin pregnancies and to investigate the role of maternal and placental compartments in marker production by comparing the levels of the decidual cytokine M-CSF with the PAPP-A and SP1 from the placenta. Methods Thirteen twin pregnancies with at least one chromosomally abnormal fetus were compared with 68 normal twin pregnancies. Sera were obtained between 11 + 3 and 13 + 6 weeks of gestation, and PAPP-A, SP1 and M-CSF levels were determined by immunoassay. These concentrations were also compared with gestation-matched groups of 18 singleton normal pregnancies and 18 singleton Down syndrome pregnancies. Results PAPP-A and SP1, but not M-CSF, levels were higher in normal twin pregnancy than in normal singleton pregnancy. SP1 levels, but not PAPP-A, correlated to M-CSF. PAPP-A, but not SP1, levels were reduced in abnormal twin pregnancies, with an increasing effect according to the number of affected fetuses, and were more pronounced in pregnancies with trisomy 18 or 13 than in trisomy 21 fetuses. M-CSF was inconsistent, with a trend towards increased levels in trisomy 21. Conclusion PAPP-A remains the best biochemical screening marker for fetal trisomies 21, 18 or 13, in singleton as well as in twin pregnancy. In contrast to SP1, its site of production is not likely to be restricted to the placenta. The role of the (maternally produced) M-CSF remains to be further investigated. Copyright © 2003 John Wiley & Sons, Ltd.

We have examined maternal urine concentrations of beta core, free beta human chorionic gonadotrophin (hCG), and total oestriol in 373 control pregnancies and 43 pregnancies affected by aneuploidy (including 22 cases of Down's syndrome) in an attempt to see if any of the analytes have a value in Down's syndrome screening between the tenth and 14th week of pregnancy. We have compared the performance of these analytes against nuchal translucency measurement combined with maternal serum free beta hCG at the same period of pregnancy. Our results show that levels of urine free beta hCG and beta core are increased in Down's syndrome with average multiple of the median levels of 1.81 and 2.91, respectively. Urine total oestriol was reduced (0.83) whilst maternal serum free beta hCG was increased (1.72). In trisomy 18 the levels of all analytes were reduced, although serum free beta hCG was the most discriminating. The spread of results in the control and the Down's group for urine beta core was more than three times than that for serum free beta hCG and with urine free beta hCG it was two times wider. In combination with maternal age, urine total oestriol had a 32 per cent detection rate at a fixed 5 per cent false-positive rate; urine beta core 34 per cent, urine free beta hCG 36 per cent, maternal serum free beta hCG 44 per cent, and nuchal translucency 82 per cent. In combination with nuchal translucency, urine total oestriol added an extra 1 per cent detection, urine beta core an extra 2 per cent, urine free beta hCG an extra 3 per cent, and serum free beta hCG an extra 5 per cent. It is unlikely that any of the urine markers will be of value in first-trimester screening. Optimal first-trimester screening programmes will rely for the foreseeable future on nuchal translucency, serum free beta hCG, and possibly pregnancy-associated plasma protein A.

Initial studies at 17-22 weeks' gestation evaluating urinary beta-core human chorionic gonadotrophin (hCG) as a marker for Down's syndrome had suggested that it may have more potential than its serum counterpart. This study measured maternal urinary beta-core-hCG and creatinine at 11-14 weeks' gestation in a series of 26 aneuploidies (nine trisomy 21, five trisomy 18, four 45,X0, and eight others). The normal range for beta-core-hCG and beta-core-hCG/creatinine was derived from 198 normal singleton pregnancies. Trisomy 18 cases (n=5) had low maternal urinary beta-core-hCG creatinine levels (median 0·35 MOM, range 0·08-0·82 MOM), whereas the other aneuploidies had no particular pattern; in particular, the trisomy 21 cases (n=9) (median 1·16 MOM, range 0·3-4·74 MOM) did not differ significantly from 1 MOM. The findings imply that maternal urinary beta-core-hCG is not as discriminating for Down's syndrome between 11 and 14 weeks as later on in pregnancy. © 1997 John Wiley & Sons, Ltd.

Objective To determine the relation between maternal serum inhibin-A and free β-hCG concentrations in chromosomally normal pregnancies and to compare the two biochemical markers for their sensitivity in identifying trisomy 21 pregnancies. Sample Inhibin-A and free β-hCG were measured in maternal serum samples from 800 chromosomally normal singleton pregnancies at 10 to 14 weeks of gestation and 76 singleton pregnancies with fetal trisomy 21. Results In the normal group maternal serum inhibin-A was significantly associated with both maternal weight and gestational age (F= 11.2, P < 0.0001). In pregnancies with trisomy 21 the maternal serum inhibin-A and free β-hCG concentrations were significantly increased (mean difference inhibin = 0.51 SD, F= 18, P < 0.0001 and mean difference free β-hCG = 1.13 SD, F= 80, P < 0.0001). For a 5% false positive rate, the sensitivity of maternal serum free β-hCG in identifying pregnancies with trisomy 21 was 28.9% compared with 12.8% for maternal serum inhibin-A. Delta inhibin-A was significantly associated with delta-free β-hCG (r= 0.345, P < 0.01) and the deviation from the normal mean for free β-hCG was significantly greater than the deviation for inhibin-A (t= 4.0, P < 0.0001). For a 5% false positive rate, the sensitivity achieved by combining information from delta inhibin-A and delta free β-hCG was similar to the sensitivity of free β-hCG alone (30.3% compared with 28.9%) Conclusion At 10 to 14 weeks of gestation fetal trisomy 21 is associated with increased maternal serum inhibin-A and free β-hCG levels. However, the degree of elevation of inhibin-A is less than that of free β-hCG, and there is a significant association between levels of the two proteins. The sensitivity for trisomy 21 achieved with the combination of maternal serum inhibin-A and free β-hCG is not significantly different from that achieved with maternal serum free β-hCG alone.

Many lines of evidence point to an important role for the insulin-like growth factors (IGFs) in embryonic and fetal growth in human pregnancy. The bioavailability of IGFs is modulated by IGF-binding proteins (IGFBP-1 to -6), whose permissive or inhibitory actions are regulated in part by posttranslational modification. In second and third trimester pregnancies, maternal IGFBP-1 is elevated in preeclampsia and intrauterine growth retardation. In the first trimester, trisomic pregnancies result in derangement of maternal serum levels of peptides, including hCG beta and pregnancy-associated plasma protein A. Trisomy 18 is characterized by growth failure in the first trimester, whereas trisomy 21 is not; thus, if maternal serum levels of IGFs and IGFBPs reflect fetal growth, changes specific to trisomy 18 may be expected. We report maternal serum levels of IGF-I, IGF-II, and IGFBP-1,-2, and -3; IGFBP-1 phosphorylation; and IGFBP-3 proteolysis in pregnancies (n = 139) complicated by trisomy 18 or trisomy 21 compared with those in normal controls. Maternal IGF-I, IGF-II, and IGFBP-3 showed no significant difference between fetuses with a normal karyotype and those with trisomy 18 or 21. The mean IGFBP-1 level was significantly higher and the mean IGFBP-2 level was lower in fetuses with trisomy 18 compared with normal fetuses [108.8 +/- 6.1 vs. 36.7 +/- 1.9 micrograms/L (P = 0.0001) and 81.2 +/- 5.5 vs. 206.1 +/- 10.2 micrograms/L (P = 0.0001), respectively]. There was no significant difference between the trisomy 21 and normal groups. The reduction in IGFBP-2 was confirmed by Western ligand and immunoblotting, and there was no evidence of variation in lower mol wt products to suggest differential proteolysis. IGFBP-1 phosphoforms and IGFBP-3 proteolysis were not significantly different between groups. The finding of altered maternal serum levels of IGFBP-1 and IGFBP-2 specific to pregnancies complicated by trisomy 18 suggests that these binding proteins may be important mediators of fetal growth in the first trimester, and the clear differences in the ratio of IGFBP-1 to -2 may serve as an additional diagnostic marker for trisomy 18 pregnancies.

New neurons are continuously produced in the subgranular zone of the adult hippocampus and can modulate hippocampal plasticity across life. Adolescence is characterized by dramatic changes in sex hormone levels, and social and emotional behaviors. It is also an age for increased risk of psychiatric disorders, including schizophrenia, which may involve altered hippocampal neurogenesis. The extent to which testosterone and other testicular hormones modulate hippocampal neurogenesis and adolescent behavioral development is unclear. This study aimed to determine if removal of testicular hormones during adolescence alters neurogenesis in the male rhesus macaque hippocampus. We used stereology to examine levels of cell proliferation, cell survival and neuronal differentiation in late adolescent male rhesus macaques (4.6-yrs old) that had previously been gonadectomized or sham operated prior to puberty (2.4-yrs old). While the absence of adolescent testicular hormones had no effect on cell proliferation, cell survival was increased by 65% and indices of immature neuronal differentiation were increased by 56% in gonadectomized monkeys compared to intact monkeys. We show for the first time that presence of circulating testicular hormones, including testosterone, may decrease neuronal survival in the primate hippocampus during adolescence. Our findings are in contrast to existing studies in adults where testosterone tends to be a pro-survival factor and demonstrate that testicular hormones may reduce hippocampal neurogenesis during the age typical of schizophrenia onset.

Fetal heart rate was measured routinely as part of a prospective study examining the efficacy of screening for trisomy 21 by fetal nuchal translucency thickness and maternal age. In 6903 normal singleton pregnancies the fetal heart rate decreased from a mean of 171 bpm at 10 weeks of gestation to 156 bpm at 14 weeks (r = 0.413, p < 0.0001). In 85 trisomy 21 pregnancies, the mean heart rate was significantly higher than in the normal group (mean difference 0.67 SD, 95% confidence interval 0.42-0.92, t = 5.3, p < 0.001). The fetal heart rate in trisomy 18 and triploid fetuses was significantly lower and in trisomy 13 and Turner syndrome was higher than normal. There was no significant association between delta fetal heart rate and delta nuchal translucency thickness in either the normal (r = -0.018) or the trisomy 21 (r = -0.031) pregnancies. Consequently, the risk for chromosomal defects can be derived by combining data from maternal age, fetal nuchal translucency and fetal heart rate. The effectiveness of screening by this method was examined in a self-selected population with completed pregnancies that had undergone first-trimester scanning. This population contained 6903 normal and 29 trisomy 21 fetuses. For a false-positive rate of about 5%, the sensitivity for trisomy 21 was 48% by maternal age, 26% by fetal heart rate, 72% by nuchal translucency thickness, 59% by maternal age and fetal heart rate, 76% by maternal age and nuchal translucency thickness and 83% by a combination of maternal age, nuchal translucency thickness and fetal heart rate.

In 176 diamniotic twin pregnancies at 10-20 weeks of gestation, amniotic fluid for cytogenetic studies was successfully obtained from both sacs by the use of a single uterine entry. There were no cases of discordancy between sex at amniocentesis and birth. There were six pregnancies with fetal unbalanced chromosomal defects; in one pregnancy both fetuses were abnormal and in five pregnancies only one fetus was abnormal. The total fetal loss rate was 5.7% (20 of 352 fetuses), including six (1.7%) terminations or selective fetocides and 14 (4.0%) spontaneous deaths. In the 176 pregnancies there were five (2.8%) with no survivors, including one termination and four (2.3%) spontaneous miscarriages or intrauterine deaths. There are only two (1.1%) pregnancies in which amniocentesis could have contributed directly to the losses and therefore the procedure-related rate of fetal loss may be similar to that in singleton pregnancies. The median gestation at delivery was 37 (range 16-40) weeks and delivery before 32 weeks occurred in 9% of the pregnancies. The birth weight distribution was similar to that reported in singleton pregnancies. This study demonstrates that in twin pregnancies amniotic fluid for cytogenetic studies can be obtained successfully from both sacs by use of a single uterine entry. The risk of fetal loss from this procedure appears to be similar to that in singleton pregnancies.

The aim of this prospective study was to measure the contribution of maternal serum free β-human chorionic gonadotropin (β-hCG) in a screening program for fetal trisomy 21 based on fetal nuchal translucency in the first trimester of pregnancy. The maternal serum was collected at the time of the ultrasound scan and assayed without knowledge of the nuchal translucency measurement or karyotype. A total of 2529 pregnancies were examined (normal group, n = 2427: trisomy 21 group, n = 102). Maternal serum free β-hCG was significantly associated with gestational age and maternal weight. In the trisomy 21 group the free β-hCG was significantly higher than in the normals, being above the 95th centile in 29% of the cases. There was no significant association between the deviation from the mean for free β-hCG and nuchal translucency thickness in either the normal or the trisomy 21 groups. When maternal serum free β-hCG was added to a model based on maternal age and fetal nuchal translucency thickness, the detection rate for trisomy 21 was increased from 80% to 85%. Copyright © 1995 International Society of Ultrasound in Obstetrics and Gynecology

Protein S100 is a low molecular weight (10-12 kD) calcium-binding protein the beta subunit of which is coded for at the 22.2-22.3 region of the long arm of chromosome 21. This region has also been shown to be responsible for the phenotypic expression of Down syndrome. Previous studies demonstrated increased immunoreactivity to protein S100 in brain tissue from adults with Down syndrome. We have previously observed a higher concentration of S100 protein in the fetal blood of trisomy 21 fetuses compared with normal subjects. The aim of this study was therefore to investigate the use of measuring S100 protein concentration in maternal blood for Down syndrome screening. Maternal blood was taken at the time of chorionic villus sampling or cordocentesis (11-38 weeks' gestation) for fetal karyotyping. Protein S100 was measured by a two-site immunoradiometric assay (S-100 IRMA, Sangtec). There was no significant difference in the concentration of maternal S100 protein between normal and trisomy 21 pregnancies (p

In three cases of lumbosacral spina bifida diagnosed at 12, 13 and 14 weeks of gestation there was an associated lemon sign, or scalloping of the frontal bones, and in one case the fetal nuchal translucency was increased. In a multicenter ultrasound screening study at 10-14 weeks there were 61,972 singleton pregnancies including 29 cases of spina bifida, none of which was diagnosed at the routine first-trimester scan, but 28 of the 29 cases were detected by ultrasonography at 16-22 weeks; in one case the diagnosis was missed at the 20-week scan and the defect was identified at 32 weeks during a scan for localization of the placenta. The fetal nuchal translucency was above the 95th centile in only one of the cases (3.4%). It is possible that the majority of fetuses with spina bifida have a lemon sign in the first trimester, but the sensitivity of the 10-14-week scan in the diagnosis of spina bifida and the prevalence of the lemon sign at this gestation will only be established by further studies incorporating early systematic examination of the head and spine.

Protein S100 is a low molecular weight (10-12 kD) calcium-binding protein the beta subunit of which is coded for at the 22.2-22.3 region of the long arm of chromosome 21. This region has also been shown to be responsible for the phenotypic expression of Down syndrome. Previous studies demonstrated increased immunoreactivity to protein S100 in brain tissue from adults with Down syndrome. We have previously observed a higher concentration of S100 protein in the fetal blood of trisomy 21 fetuses compared with normal subjects. The aim of this study was therefore to investigate the use of measuring S100 protein concentration in maternal blood for Down syndrome screening. Maternal blood was taken at the time of chorionic villus sampling or cordocentesis (11-38 weeks' gestation) for fetal karyotyping. Protein S100 was measured by a two-site immunoradiometric assay (S-100 IRMA, Sangtec). There was no significant difference in the concentration of maternal S100 protein between normal and trisomy 21 pregnancies (p0.10). Moreover, there was no significant association between maternal serum S100 protein concentration and gestational age (r(s)=0.27, p=0.07), maternal age (r(s)=-0.17, p=0.7) or maternal weight (r(s)=-0.013, p=0.9). This study shows that measurement of maternal serum S100 protein concentration does not appear to have a value in Down syndrome screening.

Maternal serum free beta-hCG was measured at 10 to 14 weeks of gestation in 136 normal twin pregnancies and in 12 twin pregnancies where one or both fetuses had trisomy 21. The values were compared with a normal range from 4181 singleton pregnancies. In the normal twins the median free beta-hCG (65 ng/mL) was about twice as high as in singletons (34 ng/mL z = -12.1, P < 0.0001). In the trisomy 21 group the median free beta-hCG (95 ng/mL) was significantly higher than in normal twins (z = 2.1, P < 0.05). However, only one of the trisomic pregnancies had a level above the 95th centile. In twin pregnancies maternal serum free beta-hCG at 10 to 14 weeks of gestation is unlikely to be useful in the prediction of fetal trisomy 21.

Fetal heart rate was measured routinely as part of a prospective study examining the efficacy of screening for trisomy 21 by fetal nuchal translucency thickness and maternal age. In 6903 normal singleton pregnancies the fetal heart rate decreased from a mean of 171 bpm at 10 weeks of gestation to 156 bpm at 14 weeks (r = 0.413, p0.0001). In 85 trisomy 21 pregnancies, the mean heart rate was significantly higher than in the normal group (mean difference 0.67 SD, 95% confidence interval 0.42-0.92, t = 5.3, p0.001). The fetal heart rate in trisomy 18 and triploid fetuses was significantly lower and in trisomy 13 and Turner syndrome was higher than normal. There was no significant association between delta fetal heart rate and delta nuchal translucency thickness in either the normal (r = -0.018) or the trisomy 21 (r = -0.031) pregnancies. Consequently, the risk for chromosomal defects can be derived by combining data from maternal age, fetal nuchal translucency and fetal heart rate. The effectiveness of screening by this method was examined in a self-selected population with completed pregnancies that had undergone first-trimester scanning. This population contained 6903 normal and 29 trisomy 21 fetuses. For a false-positive rate of about 5%, the sensitivity for trisomy 21 was 48% by maternal age, 26% by fetal heart rate, 72% by nuchal translucency thickness, 59% by maternal age and fetal heart rate, 76% by maternal age and nuchal translucency thickness and 83% by a combination of maternal age, nuchal translucency thickness and fetal heart rate.

In 176 diamniotic twin pregnancies at 10-20 weeks of gestation, amniotic fluid for cytogenetic studies was successfully obtained from both sacs by the use of a single uterine entry. There were no cases of discordancy between sex at amniocentesis and birth. There were six pregnancies with fetal unbalanced chromosomal defects; in one pregnancy both fetuses were abnormal and in five pregnancies only one fetus was abnormal. The total fetal loss rate was 5.7% (20 of 352 fetuses), including six (1.7%) terminations or selective fetocides and 14 (4.0%) spontaneous deaths. In the 176 pregnancies there were five (2.8%) with no survivors, including one termination and four (2.3%) spontaneous miscarriages or intrauterine deaths. There are only two (1.1%) pregnancies in which amniocentesis could have contributed directly to the losses and therefore the procedure-related rate of fetal loss may be similar to that in singleton pregnancies. The median gestation at delivery was 37 (range 16-40) weeks and delivery before 32 weeks occurred in 9% of the pregnancies. The birth weight distribution was similar to that reported in singleton pregnancies. This study demonstrates that in twin pregnancies amniotic fluid for cytogenetic studies can be obtained successfully from both sacs by use of a single uterine entry. The risk of fetal loss from this procedure appears to be similar to that in singleton pregnancies.

The aim of this prospective study was to measure the contribution of maternal serum free beta-human chorionic gonadotropin (beta-hCG) in a screening program for fetal trisomy 21 based on fetal nuchal translucency in the first trimester of pregnancy. The maternal serum was collected at the time of the ultrasound scan and assayed without knowledge of the nuchal translucency measurement or karyotype. A total of 2529 pregnancies were examined (normal group, n = 2427; trisomy 21 group, n = 102). Maternal serum free beta-hCG was significantly associated with gestational age and maternal weight. In the trisomy 21 group the free beta-hCG was significantly higher than in the normals, being above the 95th centile in 29% of the cases. There was no significant association between the deviation from the mean for free beta-hCG and nuchal translucency thickness in either the normal or the trisomy 21 groups. When maternal serum free beta-hCG was added to a model based on maternal age and fetal nuchal translucency thickness, the detection rate for trisomy 21 was increased from 80% to 85%.

Objective To examine the usefulness of selecting the appropriate techque for fetal karyotyping in twin pregnancies by using maternal age and fetal nuchal translucency thickness to determine risk for chromosomal defects in each fetus. Setting Fetal Medicine Centre, London, United Kingdom. Subjects Sixty-seven twin pregnancies identified at the time of an ultrasound scan for determination of fetal nuchal translucency thickness, where the parents requested karyotyping. Intervention The risk for chromosomal defects in each fetus was calculated from the maternal age and fetal nuchal translucency thickness at 10 to 14 weeks of gestation. If the estimated risk for either fetus was 1 in 50 or greater, chorion villus sampling was the method of choice, whereas if the risk was less than 1 in 50 second trimester amniocentesis was performed. Results The estimated risk for trisomies was more than 1 in 50 in 34 pregnancies and 23.5% of these fetuses were found to be chromosomally abnormal. In contrast, in the 33 low risk pregnancies chromosomal abnormalities were found in only 1.5% of the fetuses. Conclusions In twin pregnancies the technique for fetal karyotyping may be selected by calculating the risk for chromosomal abnormality based on maternal age and fetal nuchal translucency thickness.

Objective To examine options of management and outcome of twin pregnancies discordant for anencephaly. Design Retrospective study. Setting Research Centre for Fetal Medicine. Population Twenty-four twin pregnancies discordant for anencephaly. Methods A computer search was made of our database for twin pregnancies discordant for anencephaly. The data were reviewed for gestation at presentation, chorionicity, management and pregnancy outcome. Main outcome measures Pregnancy outcome in relation to chorionicity and management. Results There were 13 dichorionic and 11 monochorionic twin pregnancies discordant for anencephaly. In the dichorionic group five pregnancies had selective fetocide at 17 to 21 weeks; one pregnancy resulted in spontaneous abortion but in the others a healthy infant was born at a median gestation of 37 weeks. The other eight dichorionic pregnancies were managed expectantly, but three developed polyhydramios at 26 to 30 weeks; in one case amniodrainage was performed and in another selective fetocide was carried out. In this group the median gestation at delivery was 35 weeks. All 11 monochorionic pregnancies were managed expectantly and in three there was intrauterine death of both fetuses. In the other eight cases the normal twin was liveborn at a median gestation of 34 weeks; in four of these pregnancies polyhydramnios developed and two were managed by amniodrainage. Conclusions In monochorionic pregnancies, expectant management is associated with a high rate of intrauterine lethality of the normal twin. In dichorionic pregnancies selective fetocide in the second trimester prevents the development of polyhydramnios and is associated with a lower risk of preterm delivery but can cause miscarriage.