Thermomechanical model to assess stresses developed during elevated-temperature cleaning of coated optics.

A thermomechanical model is developed to estimate the stress response of an oxide coating to elevated-temperature chemical cleaning. Using a hafnia-silica multilayer dielectric pulse compressor grating as a case study, we demonstrate that substrate thickness can strongly affect the thermal stress response of the thin-film coating. As a result, coatings on large, thick substrates may be susceptible to modes of stress-induced failure (crazing or delamination) not seen in small parts. We compare the stress response of meter-scale optics to the behavior of small-scale test or "witness" samples, which are expected to be representative of their full-size counterparts. The effects of materials selection, solution temperature, and heating/cooling rates are explored. Extending the model to other situations, thermal stress results are surveyed for various combinations of commonly used materials. Seven oxide coatings (hafnia, silica, tantala, niobia, alumina, and multilayers of hafnia-silica and alumina-silica) and three glass substrates (BK7, borosilicate float glass, and fused silica) are examined to highlight some interesting results.

Fracture mechanics of delamination defects in multilayer dielectric coatings.

During the fabrication of multilayer-dielectric (MLD) thin-film-coated optics, such as the diffraction gratings used in OMEGA EP's pulse compressors, acid piranha cleaning can lead to the formation of chemically induced delamination defects. We investigate the causes of these defects and describe a mechanism for the deformation and failure of the MLD coating in response to hydrogen peroxide in the cleaning solution. A fracture mechanics model is developed and used to calculate the crack path that maximizes the energy-release rate, which is found to be consistent with the characteristic fracture pattern observed in MLD coating delamination defects.

Nuclear localisation of the endocannabinoid metabolizing enzyme fatty acid amide hydrolase (FAAH) in invasive trophoblasts and an association with recurrent miscarriage.

Endocannabinoids are lipid signalling molecules that are related to the major psychoactive component in marijuana, delta-9-tetrahydrocannabinol and are increasingly recognized as being important in implantation and development of early embryos. The endocannabinoid anandamide, is metabolized by the enzyme fatty acid amide hydrolase (FAAH), and insufficient levels of this enzyme have been implicated in spontaneous miscarriage in women and implantation failure in mice. We screened placental bed biopsies and placental tissue from 45 women with recurrent miscarriage and 17 gestation-matched women with normal pregnancies for the expression of FAAH by immunohistochemistry. Unexpectedly, the enzyme appeared to be localised to the nucleus of trophoblasts and this was confirmed by western blotting of sub-cellular fractions and confocal microscopy. FAAH was expressed in the cytoplasm of large decidual stromal cells and significantly more women with recurrent miscarriage (73%) expressed FAAH in these cells than women with normal pregnancy (31%). FAAH was also expressed in the nucleus of extravillous trophoblasts that had invaded the decidua from 67% of women with recurrent miscarriage but was not expressed by these cells in any women with normal pregnancies. In contrast, FAAH was expressed in extravillous trophoblasts that had migrated out of the villi but that had not yet invaded the decidua in both normal pregnancies and in cases of recurrent miscarriage. FAAH was also present in the nucleus of a small number of villous trophoblasts in some specimens. FAAH appears to be over expressed in trophoblasts that have invaded the decidua, as well as in large decidual stromal cells in many cases of recurrent miscarriage. This may reflect inadequate control of the cannabinoid system in the uterus of women who experience recurrent miscarriages. The functional significance of the unexpected nuclear localisation of FAAH in trophoblasts is not yet clear.

Comparison of the expression of human leukocyte antigen (HLA)-G and HLA-E in women with normal pregnancy and those with recurrent miscarriage.

Recurrent miscarriage affects 1% of all couples attempting pregnancy. Immunological factors are postulated to play a role in the aetiology of recurrent miscarriage because the fetus and placenta are immunologically different from the mother. In particular, altered expression of the, non-classical, class I histocompatibility leukocyte antigen (HLA) molecules has been postulated to play a role in the aetiology of recurrent miscarriage as the fetus and placenta are semi-allogenic to the mother. This study was conducted to examine whether altered expression of the non-classical class I HLA molecules, HLA-G and HLA-E, by cells at the maternofetal interface could play a role in the aetiology of recurrent miscarriage. First-trimester placental and decidual biopsies were obtained from 45 women with recurrent miscarriage and 17 gestation-matched normal controls. These biopsies were screened by immunohistochemistry for HLA-G and HLA-E and isotype-matched control antibodies. Staining was analysed by light microscopy and digital image analysis. In both recurrent miscarriage and normal pregnancy, HLA-G was localised to the extravillous trophoblast. There was no difference in the pattern of HLA-G expression between women with recurrent miscarriage and those with normal pregnancies. HLA-E was localised to the syncytiotrophoblast, villous mesenchymal cells, extravillous trophoblast and several decidual cell types, but staining for HLA-E appeared to be confined primarily to the cytoplasm. There was no difference in the pattern of HLA-E expression between women with recurrent miscarriage and those with normal pregnancies.

CD83(+)dendritic cells in the decidua of women with recurrent miscarriage and normal pregnancy.

Immunological factors have been postulated to play a role in the aetiology of recurrent miscarriage as the fetus and placenta are semi-allogenic to the mother. Potent immunostimulatory (CD83(+)) dendritic cells have recently been identified in the uterine decidua. This study was conducted to examine whether decidual dendritic cells could play a role in the aetiology of recurrent miscarriage. First trimester placental and decidual biopsies were obtained from 40 women with recurrent miscarriage and 15 gestation-matched normal controls. These biopsies were screened by immunohistochemistry for CD83(+)cells. Staining was analysed by light microscopy and digital image analysis. In both recurrent miscarriage and normal pregnancy, CD83(+)dendritic cells were localized to the decidua. Individual dendritic cells were present in the decidual stroma or in clusters of 3-4 dendritic cells, in lymphoid aggregates. There were no significant differences in decidual CD83(+)dendritic cell density between women with recurrent miscarriage and normal pregnancy when the groups were compared as a whole. However, when segregated by gestational age, decidua from women with recurrent miscarriage at 8 weeks' gestation contained significantly more dendritic cells than gestational age-matched normal controls. This suggests dendritic cells may play a role in the aetiology of some cases of recurrent miscarriage.

Does aspirin have a role in improving pregnancy outcome for women with the antiphospholipid syndrome? A randomized controlled trial.

OBJECTIVE: This pilot investigation was undertaken to assess the efficacy of low-dose aspirin therapy for the treatment of women with antiphospholipid antibodies when recurrent miscarriage is the only sequela. STUDY DESIGN: A double-blind, randomized, placebo-controlled trial was conducted in the setting of the recurrent miscarriage clinic of a tertiary referral obstetric hospital. The participants were 50 women with a history of recurrent miscarriages (>/=3) and antiphospholipid antibodies. Women with systemic lupus erythematosus or a history of thrombosis were excluded. Women were recruited after full investigative screening at the recurrent miscarriage clinic. Women with >/=3 fetal losses and persistently positive results for antiphospholipid antibodies were randomly allocated to receive either aspirin (75 mg daily) or placebo. Investigators, clinicians, and patients were blinded to the treatment. Rates of live births, antenatal complications, and delivery and neonatal outcomes were recorded prospectively. Data were compared by chi(2) analysis with Yates' correction, the Fisher exact test, or the Student t test as appropriate. RESULTS: There were 10 exclusions after random assignment because of inappropriate inclusion. Eighty-five percent of the placebo (17/20) group and 80% of the aspirin-treated group (16/20) were delivered of live infants. This difference was not significant. There were no significant differences in antenatal complications or neonatal morbidity between the groups. CONCLUSIONS: This preliminary study suggests that low-dose aspirin has no additional benefit when added to supportive care for women for whom recurrent early fetal loss is the only sequela of the antiphospholipid syndrome. This live birth rate with supportive care alone exceeds the published live birth rates for women with antiphospholipid antibody-mediated recurrent fetal loss who were treated with heparin or corticosteroids. This trial, like all other trials in this field, is small, but its results bring into question the need for pharmacologic intervention for women with antiphospholipid syndrome for whom recurrent fetal loss is the only sequela. Our results highlight the need for a large randomized controlled trial to identify the optimal treatment for this group of women and justify the inclusion of a placebo arm in any such trial.

Recurrent miscarriage: screening for polycystic ovaries and subsequent pregnancy outcome.

A population of women with a history of recurrent miscarriage were screened for polycystic ovaries (PCO) by an ultrasound, LH, FSH, free testosterone in the follicular phase, then luteal phase progesterone and body mass index (BMI). Twenty six of the 73 women screened (36%) had an ultrasound demonstrating PCO; of these 21 (81%) became pregnant and 17 were given supportive and observational care only. The miscarriage rate was 18% with 14 (82%) having livebirths. Twenty seven of the 47 women with normal ovaries (74%) became pregnant; 31 had supportive care only and 6 (19%) miscarried with 25 (81%) having a livebirth. We conclude that the ultrasound diagnosis of PCO in women with a history of recurrent miscarriage does not necessarily predict a poor outcome in subsequent pregnancy.

Serum concentrations of human chorionic gonadotrophin and immunoreactive inhibin in early pregnancy and recurrent miscarriage: a longitudinal study.

Serum concentrations of immunoreactive inhibin (ir-inhibin) and human chorionic gonadotrophin (HCG) have been measured during the first trimester in a longitudinal study of pregnant women attending a recurrent miscarriage clinic. In 30 singleton pregnancies (Group 1) that continued successfully to term, the median concentration of ir-inhibin initially declined from 1,140 pg/mL at week 4-5 then rose back to comparable values between weeks 7 and 10 but to decline again to reach the significantly lower level of 840 pg/mL (p < 0.01) at week 15-16. Serum levels of HCG showed the classical profile of normal pregnancy reaching a median peak value of 65,600 IU/L (1st IRP) at week 8-9. In 7 pregnancies that miscarried but earlier had evidence on ultrasound of an active fetal heart, HCG levels in the first 9 weeks were consistently below the 10th percentile for Group 1 pregnancies (p < 0.001). Levels of ir-inhibin were also suppressed but to a lesser extent. In 6 of 7 a fetal pregnancies, HCG levels during the first 9 weeks were again markedly subnormal. The levels of ir-inhibin varied between high normal and subnormal. In none of the pregnancy groups was a correlation found between ir-inhibin and HCG concentrations. In a single pregnancy with an anencephalic fetus, while levels of ir-inhibin and HCG were not depressed, peak values were not reached until week 12. The study shows that the level of ir-inhibin in the maternal serum in early pregnancy is of little value as a prognostic indicator of pregnancy outcome. It confirms that a subnormal HCG level is a useful predictor of early pregnancy failure.

Recurrent miscarriage--outcome after supportive care in early pregnancy.

One hundred and thirty three couples were investigated at a recurrent miscarriage clinic. In their next pregnancy 42 women (Group 1) with unexplained recurrent miscarriage were managed with a programme of formal emotional support and close supervision at an early pregnancy clinic. Two women were seen in 2 pregnancies (44 supervised pregnancies); 86% (38 of 44) of these pregnancies were successful. Four of the 6 miscarriages had an identifiable causal factor. Nine women (Group 2), also with unexplained recurrent miscarriage, acted as a control group. After initial investigation they were reassured and returned to the care of their family practitioner and did not receive formal supportive care in their subsequent pregnancy; 33% (3 of 9) of these pregnancies were successful (p = 0.005; Fishers Exact Test). Whilst acknowledging that there is a significant spontaneous cure rate in this condition, emotional support seems to be important in the prevention of unexplained recurrent miscarriage, giving results as good as any currently accepted therapy.

Outcome of pregnancies progressing beyond 28 weeks gestation in women with a history of recurrent miscarriage.

Ninety-seven women who had had three or more miscarriages had also had at least one pregnancy with a singleton birth that had reached 28 weeks gestation. Information was available on these 118 babies: 30% were small-for-gestational age (birthweight less than or equal to 10th centile using figures from Scotland 1973-79), 28% were born preterm, and the perinatal mortality rate (excluding babies of less than 28 weeks gestation) was 161/1000 births, all of which are significantly increased above the prevalence for a normal obstetric population. These observations may serve to alert the clinician to the increased risk of these complications when dealing with women who have a history of recurrent miscarriage.

Defective haemochorial placentation as a cause of miscarriage: a preliminary study.

The morphology of the placental bed in idiopathic sporadic and recurrent miscarriages was studied and the findings correlated with the fetal chromosomal pattern where possible. Defective development of haemochorial placentation, which was not necessarily linked with fetal chromosomal abnormality, was seen in association with some miscarriages. These preliminary results, not previously demonstrated, strongly support the concept that miscarriages and pregnancies complicated by pre-eclampsia and/or small-for-gestational-age infants may be a continuum of disorders with a similar pathology in the placental bed.