Optical polymers with tunable refractive index for nanoimprint technologies.

In order to realize a versatile high throughput production of micro-optical elements, UV-curable polymer composites containing titanium dioxide nanoparticles were prepared and characterized. The composites are based on an industrial prototype epoxy polymer. Titanium dioxide nanoparticles smaller than 10 nm were synthesized by the nonaqueous sol method and in situ sterically stabilized by three different organic surfactants. The composites exhibit high transparency. Distinct alteration of optical transmission properties for visible light and near IR wavelength range could be avoided by adaption of the stabilizing organic surfactant. Most importantly, the refractive index (RI) of the composites that depends on the fraction of incorporated inorganic nanoparticles could be directly tuned. E.g. the RI at a wavelength of 635 nm of a composite containing 23 wt% titanium dioxide nanoparticles is increased to 1.626, with respect to a value of 1.542 for the pure polymer. Furthermore, it could be demonstrated that the prepared inorganic-organic nanocomposites are well suited for the direct fabrication of low-cost micro-optical elements by nanoimprint lithography. A low response of the optical composite properties to temperature treatment up to 220 °C with a shrinkage of only about 4% ensures its application for integrated micro-optical elements in industrial production.

500,000-year stable carbon isotopic record from devils hole, nevada.

The record of carbon-13 (delta(13)C) variations in DH-11 vein calcite core from Devils Hole, Nevada, shows four prominent minima near glacial terminations (glacial-interglacial transitions) V to II. The delta(13)C time series is inversely correlated with the DH-11 oxygen isotope ratio time series and leads it by as much as 7000 years. The delta(13)C variations likely record fluctuations in the delta(13)C of dissolved inorganic carbon of water recharging the aquifer. How such variations are transported 80 kilometers to Devils Hole without obliteration by water-rock reaction remains an enigma. The record may reflect (i) global variations in the delta(13)C of atmospheric CO(2) and, hence, the delta(13)C of continental biomass or (ii) variations in extent and density of vegetation in the southern Great Basin. In the latter case, delta(13)C minima at 414, 334, 246, and 133 thousand years ago mark times of maximum vegetation.

Continuous 500,000-year climate record from vein calcite in devils hole, nevada.

Oxygen-18 (delta(18)O) variations in a 36-centimeter-long core (DH-11) of vein calcite from Devils Hole, Nevada, yield an uninterrupted 500,000-year paleotemperature record that closely mimics all major features in the Vostok (Antarctica) paleotemperature and marine delta(18)O ice-volume records. The chronology for this continental record is based on 21 replicated mass-spectrometric uranium-series dates. Between the middle and latest Pleistocene, the duration of the last four glacial cycles recorded in the calcite increased from 80,000 to 130,000 years; this variation suggests that major climate changes were aperiodic. The timing of specific climatic events indicates that orbitally controlled variations in solar insolation were not a major factor in triggering deglaciations. Interglacial climates lasted about 20,000 years. Collectively, these observations are inconsistent with the Milankovitch hypothesis for the origin of the Pleistocene glacial cycles but they are consistent with the thesis that these cycles originated from internal nonlinear feedbacks within the atmosphere-ice sheet-ocean system.

Mass-Spectrometric 230Th-234U-238U Dating of the Devils Hole Calcite Vein.

The Devils Hole calcite vein contains a long-term climatic record, but requires accurate chronologic control for its interpretation. Mass-spectrometric U-series ages for samples from core DH-11 yielded (230)Th ages with precisions ranging from less than 1,000 years (2sigma) for samples younger than approximately 140 ka (thousands of years ago) to less than 50,000 years for the oldest samples ( approximately 566 ka). The (234)U/(238)U ages could be determined to a precision of approximately 20,000 years for all ages. Calcite accumulated continuously from 566 ka until approximately 60 ka at an average rate of 0.7 millimeter per 10(3) years. The precise agreement between replicte analyses and the concordance of the (230)Th/(238)U (234)U/(238)U ages for the oldest samples indicate that the DH-11 samples were closed systems and validate the dating technique in general.

Structure of the human insulin-like growth factor binding protein-2 gene.

Insulin-like growth factors (IGFs) are polypeptide hormones with structural homology to proinsulin. IGFs circulate in blood bound to specific IGF binding proteins (IGFBPs). cDNA sequences of six members of a family of human and rat IGFBPs have been published. Here we present a partial characterization of the human IGFBP-2 gene. This single copy gene is located on chromosome 2 and spans a total of more than 32 kilobases (kb) of genomic sequence. It is organized in four exons with sizes of more than 568, 220, 141, and 496 nucleotides. The intron between exon one and exon two contributes 27 kb to the size of the IGFBP-2 gene. The second and the third introns comprise 1.1 kb and 1.95 kb, respectively. When the structure of the IGFBP-2 gene is compared to that of the IGFBP-1 and IGFBP-3 genes, the exon boundaries are found to be conserved in these three genes. A single transcriptional start site was localized to 113 +/- 2 nucleotides 5' of the ATG start codon of IGFBP-2 translation. Furthermore, the region between nucleotides -635 and -2 upstream of the ATG was demonstrated to exhibit promoter activity in human Jurkat K16 cells. This region is devoid of TATA or CAAT consensus sequence motifs and has a high content of dC and dG nucleotides. In this respect the putative IGFBP-2 promoter region resembles the promoters which are often associated with housekeeping genes.

A low molecular weight insulin-like growth factor binding protein from rat: cDNA cloning and tissue distribution of its messenger RNA.

Rat serum contains two major forms of insulin-like growth factor (IGF) binding proteins (BPs) that have apparent mol wts of about 35,000 and 150,000. We have isolated a cDNA clone encoding an IGF-BP whose N-terminal sequence is completely homologous to the NH2-terminal of the Buffalo rat liver cells-3A BP. The 270 amino acid mature protein has a predicted mol wt of 29,500. It contains a cysteine rich domain at each end of the molecule and an Arg-Gly-Asp (RGD) tripeptide motif near its C-terminus which suggests that this BP might associate with integrin cell surface receptors. The mature protein shares only partial homology with two published human IGF-BPs. Northern blot analysis shows that its mRNA is abundant in several fetal tissues, in adult brain, testes, ovaries, and kidney. Expression in the liver is high in fetal life but decreases to a barely detectable level in adulthood. However, upon hypophysectomy, the mRNA level increases at least 20-fold which suggests a hormonal regulation for the hepatic production of this small IGF-BP.

Cloning and characterization of the gene encoding murine insulin-like growth factor-binding protein-2, mIGFBP-2.

We present a characterization of the single-copy gene, mIGFBP-2, encoding the murine insulin-like growth factor-binding protein-2 (mIGFBP-2). It consists of four exons with sizes of 470 +/- 2, 227, 141 and > 475 nucleotides (nt). The first intron spans 23 kb of genomic sequence, and the complete gene extends to more than 28 kb. Two kb of the 5'-flanking region were sequenced. This region has no TATA or CAAT boxes but is G+G-rich and contains several potential regulatory sequence motifs. A total of five GC boxes, which may serve as potential binding sites for a transcription factor, Sp1, are present immediately upstream of the transcription start point (tsp). By primer extension, we identified a single tsp at nt position -85 +/- 2. The murine IGFBP-2 locus was mapped to the proximal region of mouse chromosome 1, to a region of conserved synteny with human chromosome 2q. A comparison of the deduced amino acid sequences of mouse, rat and human IGFBP-2 reveals a high degree of homology between all three species.

Maternal neurosurgical shunts and pregnancy outcome.

OBJECTIVE: To assess pregnancy outcome in women with ventriculoperitoneal or lumboperitoneal shunts. METHODS: Charts were reviewed retrospectively for mothers with ventriculoperitoneal or lumboperitoneal shunts delivered at Hutzel Hospital from 1976-1992. Patients were identified by cross-referencing medical records from Children's Hospital Neurosurgical Division and medical records at Hutzel Hospital during this period. RESULTS: Eight patients with 25 pregnancies were identified from 1976-1992. Indications for shunt placement were pseudotumor cerebri (four with lumboperitoneal shunts) and congenital hydrocephalus (four with ventriculoperitoneal shunts). Pregnancy outcomes were two elective abortions, five spontaneous abortions, two preterm vaginal deliveries, one mid-forceps rotation, two primary low transverse cesareans, two repeat low transverse cesareans, and 11 spontaneous vaginal deliveries. No patient received prophylactic antibiotics during labor and vaginal delivery because of the shunt. There were no shunt-related complications. CONCLUSIONS: This series doubles the number of previously reported pregnancy outcomes in women with neurosurgical shunts. Contrary to the literature suggesting cesarean delivery and prophylactic antibiotics for all patients, our experience suggests that vaginal delivery can be considered and that prophylactic antibiotics are not an absolute necessity in uncomplicated vaginal deliveries.

Limited clinical utility of midtrimester fetal morphometric percentile rankings in screening for birth weight abnormalities.

OBJECTIVE: Our purpose was to determine whether midtrimester fetal ultrasonographic morphometric percentile rankings are sensitive screening tests for preterm labor or birth weight abnormalities. STUDY DESIGN: Stepwise multiple regression and chi 2 analysis were used to identify midtrimester fetal measurements predicting birth weight and gestational age. Receiver-operator characteristics curves were used to evaluate abdominal circumference percentiles as a test for large-for-gestational-age and small-for-gestational-age infants. RESULTS: Extremes in abdominal circumference and head measurement percentiles were associated with large- and small-for gestational-age infants but not with preterm delivery. Abdominal circumference predicted birth weight in regression analysis; however, receiver-operator characteristic curves showed abdominal circumference percentiles to be poor screening tests for large- or small-for-gestational-age infants. The positive predictive value of 10th and 90th abdominal circumference percentiles for small- and large-for-gestational-age infants was < 20%. CONCLUSION: Midtrimester percentile rankings offer no clear benefit in targeting fetuses with potential birth weight abnormalities or risk of preterm delivery and may provide clinically misleading information.

Limited usefulness of fetal weight in predicting neonatal brachial plexus injury.

OBJECTIVE: The objectives were to determine the neonatal morbidity rate from vaginal birth and examine fetal weight-based injury-prevention strategies. STUDY DESIGN: Selected neonatal morbidities were categorized by birth weight for all vertex vaginal deliveries occurring during a 12-year period. Sensitivity, specificity, and predictive values for brachial palsy were calculated at increasing birth weight cutoff levels. A policy of cesarean delivery for macrosomic infants was evaluated. RESULTS: There were 80 cases of brachial palsy among 63,761 infants (0.13%). In mothers without diabetes, rates in the 4500- to 4999-g and >5000-g groups were 3.0% and 6.7%, respectively. A threshold of 3700 g had a sensitivity of 71% and a specificity of 86%; the positive predictive value was 0.56%. To prevent a single case of permanent injury, 155 to 588 cesarean deliveries are required at the currently recommended cutoff weight of 4500 g. CONCLUSIONS: The rates of lasting morbidity do not justify routine cesarean delivery for infants without diabetic complications weighing <5000 g.

Cloning, sequence analysis and expression of a cDNA encoding a novel insulin-like growth factor binding protein (IGFBP-2).

Insulin-like growth factors bind with high affinity to specific binding proteins in extracellular fluids. To identify structural characteristics of IGF-binding proteins that might define their physiological roles, we determined the complete primary structure of a novel human IGF-binding protein (IGFBP-2) from a cloned cDNA. The cDNA encodes a 328 amino acid IGF-binding protein precursor which contains a 39-residue signal peptide. The mature 289 amino acid IGFBP-2 has a predicted Mr of 31,325. Chinese hamster ovary (CHO) cells stably transformed with the IGFBP-2 cDNA secreted a 36 kd protein which bound, with different affinities, IGFII and IGFI, but did not bind insulin. The predicted protein sequence of this IGF-binding protein shares extensive amino acid homology (greater than 85%) with the IGF-binding protein secreted by rat BRL-3A cells, but less than 40% homology with human IGFBP-1. Therefore IGFBP-2, and not IGFBP-1 as previously suggested, represents the human homologue of the rat BRL-BP (alpha IGFBP-2). Moreover, from alignment of the predicted protein sequences of IGFBP-1 and IGFBP-2, extensive conservation of the distribution of cysteine residues is observed. Although the overall amino acid homology shared by these proteins is not high, we suggest that they represent a family of structurally related human IGFBPs. Southern blot analysis of human DNA demonstrates that IGFBP-2 is encoded by a single-copy gene, different from that of IGFBP-1.

Marked resistance of RAR gamma-deficient mice to the toxic effects of retinoic acid.

Excessive intake of retinol or of retinoic acid causes a syndrome of characteristic toxic effects known as hypervitaminosis A. To test the role of the nuclear retinoic acid receptor (RAR gamma) in this process we produced mice with a targeted disruption of the RAR gamma gene and examined toxic effects of repeated doses of retinoic acid and two other synthetic retinoids, Ro 15-1570 and Ro 40-6055. Surprisingly, homozygous mutant mice were resistant to fourfold higher doses of retinoic acid than wild-type mice as well as to elevated doses of the synthetic retinoids, indicating that RAR gamma may have a major role in mediating retinoid toxicity, a finding that possibly has practical implications for reducing the toxicity of synthetic retinoids in clinical use.

Age-related loss of bone mineral density in non-athletic and athletic women.

Single and dual photon absorptiometry were performed at the mid-radius, distal radius and lumbar spine in 1105 non-athletic and 124 athletic Caucasian women aged 18-98 years. An age-related loss of bone mineral density in mg/cm2 (BMD) occurred at the three skeletal sites. It was first demonstrated that a single break in the regression line (BMD versus Age) best fit the data. The break represented the approximate age at which an increase in the rate of bone density loss occurred. This break is termed the 'cutpoint'. The approximate (average) age at which the cutpoint occurred was determined by segmented regression analysis with bone density as the dependent variable. The age range studied was between 45 and 55 years. At all three bone sites, the cutpoints in non-athletic women occurred between 47 and 52 years of age, corresponding roughly to the time of menopause. Following this cutpoint the rate of bone loss increased at all three locations in non-athletic women. In athletic women no cutpoint in BMD values could be demonstrated for this age range for the two radial sites. The number of lumbar spine measurements in this group was too small for analysis. The absence of a significant change in rate of bone loss in athletes could have been due to the relatively small number of subjects. It could also suggest that regular sustained exercise programs may delay or minimize the increased rate of loss of BMD which occurs in non-athletic women in the perimenopausal period.

Telemedicine and fetal ultrasonography: assessment of technical performance and clinical feasibility.

OBJECTIVE: Our aim was to determine the performance and clinical feasibility of telesonography for the interpretation of fetal anatomic scans sent from a remote location compared with those obtained at a tertiary care prenatal ultrasonography center. STUDY DESIGN: Routine ultrasonographic studies from 35 patients were remotely interpreted. Evaluation included a blinded comparison of the sonographer's assessment of 38 fetal structures with that of the physician at the tertiary care center. Technical evaluation included system reliability and the number of digital telephone lines required for adequate real-time visualization. RESULTS: The mean gestational age at the time of the ultrasonography was 25.84 +/- 6.8 weeks (range 14 to 38). There was complete consistency of interpretation for 25 of 38 (66%) fetal structures. Thirteen structures had discrepancies in visualization, reflecting a difference in the adequacy of visualization, not the normalcy or identity of the structures. Three digital (integrated switching digital network, ISDN) telephone lines were required for real-time visualization. CONCLUSION: Our preliminary experience supports telesonography as a clinically useful tool for remote interpretation of fetal ultrasonographic examinations. Further studies are warranted for the continued evaluation of this emerging technology.

The apparently isolated choroid plexus cyst: importance of minor abnormalities in predicting the risk for aneuploidy.

OBJECTIVES: To assess the risk of aneuploidy in cases of isolated choroid plexus cysts (CPCs) and to compare the risk when associated with minor or major anomalies. METHODS: All fetuses with CPCs and known karyotype were identified. CPCs were categorized as 'isolated' or associated with minor or major sonographic anomalies. Preexisting risk factors for aneuploidy were compared between groups. The frequency of aneuploidy was compared between fetuses with isolated CPCs and those with CPCs associated with minor or major anomalies. Continuous and categorical variables were analyzed using one-way analysis of variance or chi-square as appropriate with p < 0.05 considered significant. RESULTS: One hundred and forty-nine fetuses with CPCs diagnosed at a mean gestational age of 19 weeks were identified. No significant differences in the frequency of preexisting risk factors for aneuploidy were identified between groups. Eighteen of 149 (12%) fetuses with CPCs had other sonographic anomalies; in 10 they were minor, and 2 of the 10 had abnormal karyotypes. Four of 8 fetuses with major anomalies were aneuploid. All 131 fetuses with isolated CPCs had normal karyotypes, and all aneuploid fetuses had additional anomalies. CONCLUSIONS: The overall rate of aneuploidy in patients with CPCs was 4% with no abnormal karyotypes among isolated CPCs. The presence of even minor sonographic abnormalities substantially increased the risk of aneuploidy. Isolated CPCs identified sonographically may not place the patient at risk of aneuploidy, but should prompt a diligent search for other minor or major anomalies. The finding of any other anomaly warrants consideration for karyotypic evaluation.

Abnormal nuchal findings on screening ultrasonography: aneuploidy stratification on the basis of ultrasonographic anomaly and gestational age at detection.

OBJECTIVE: Our purpose was to determine the specific likelihood of different aneuploidies by gestational age in patients with nuchal folds and simple and septated nuchal membranes. STUDY DESIGN: Retrospective database analysis was performed of 158 consecutive patients with a nuchal fold or simple or septated nuchal membrane on either abdominal or vaginal ultrasonography. RESULTS: Thirty-eight patients with nuchal folds, 65 with simple nuchal membranes, and 55 with septated nuchal membranes were evaluated. Septated nuchal membranes were associated with the highest incidence of karyotypic abnormalities (> 50%). A peak incidence of trisomy 21 (27%) was found in the early midtrimester, leveling off to 11% by the late midtrimester. The late first trimester had a high incidence of trisomy 18 (22%), occurring more frequently than 45,X. CONCLUSION: Ultrasonographic anomalies in the posterior neck are associated with aneuploidy from 21% to 58% of the patients in this selected population. Each anomaly has different risks for aneuploidy type, varying with gestational age at diagnosis.

Labor induction for the preterm severe pre-eclamptic patient: is it worth the effort?

OBJECTIVE: The purpose of this study was to examine the success rate of labor induction in patients with severe pre-eclampsia delivered at < or = 34 weeks' gestation; to identify factors associated with its success; and to evaluate neonatal outcomes based on induction success or failure. METHODS: We identified pregnancies complicated by severe pre-eclampsia delivered at < or = 34 weeks' at our institution from 1991 to 1998. Women who underwent labor induction and had successful vaginal delivery were compared to those who underwent labor induction, but required Cesarean delivery. Multiple logistic regression analyses were performed to assess factors associated with successful induction and neonatal outcome. RESULTS: Over the 7-year study period, there were 215 patients meeting the criteria. Sixty-four (29.8%) did not undergo a labor attempt; 69 of 151 (46%) women who underwent labor induction achieved vaginal delivery. Labor induction was successful in 0%, 6.6%, 35.3% and 68.5% of cases at 24-26, 27-28, 29-31 and 32-34 weeks' gestation, respectively. By logistic regression the only factor positively associated with successful induction was gestational age at delivery (p = 0.001), while induction for non-reassuring fetal testing was inversely associated (p = 0.02). Induction attempt, failed induction and delivery mode were not associated with increased neonatal morbidity. CONCLUSIONS: In women with severe pre-eclampsia remote from term, attempted labor induction did not appear to increase neonatal morbidity, but was rarely successful at < 28 weeks.