Sonographic Predictors of Antepartum Bleeding in Placenta Previa.

OBJECTIVE: To evaluate the association between sonographic features of placenta previa and vaginal bleeding (VB). STUDY DESIGN: Retrospective cohort study of women with placenta previa identified on ultrasound between 160/7 and 276/7 weeks gestation. Placental distance past the cervical os (DPO), placental thickness, edge angle, and cervical length (CL) were measured. The primary outcome was any VB and the secondary outcome was VB requiring delivery. Median values of the sonographic features were compared for each of the outcomes using the Mann-Whitney U test. Receiver operating characteristic curves were used to compare the predictive value of sonographic variables markers and to determine optimal cut points for each measurement. Logistic regression was used to estimate the association between each measure and the outcomes while controlling for confounders. RESULTS: Of 149 women with placenta previa, 37% had VB and 15% had VB requiring delivery. Women with VB requiring delivery had significantly more episodes of VB than those who did not require delivery for VB (1.5, interquartile range [IQR] [1-3] vs 1.0 [1-5]; p = 0.001). In univariate analysis, women with VB had decreased CL (3.9 vs. 4.2 cm; p < 0.01) compared with those without. Women with VB requiring delivery had increased DPO (2.6 cm IQR [1.7-3.3] vs. 1.5 cm [1.1-2.4], p = 0.01) compared with those without. After adjusting for confounders, only CL < 4 cm remained independently associated with increased risk of VB (adjusted odds ratio: 2.27, 95% confidence interval [1.12-4.58], p = 0.01). None of the measures were predictive of either outcome (area under the curve < 0.65). CONCLUSION: Decreased CL may be associated with risk of VB in placenta previa. KEY POINTS: · Placenta previa is associated with VB.. · Sonographic markers of placenta previa are associated with VB.. · CL is associated with VB in placenta previa, whereas placental DPO is associated with higher rates of bleeding leading to delivery..

Short single-frequency self-pulsing Brillouin-Raman distributed feedback fiber laser.

We demonstrate that the stimulated Brillouin scattering of a 250 mm long distributed feedback Raman fiber laser can self-pulse with repetition rates up to 7 MHz, pulse widths of 25 ns, and peak powers of 1.2 W. While both CW and pulsed lasing are produced from a bespoke grating at 1119 nm this laser design could be constructed at almost any wavelength, as the Raman and Brillouin gain regions are relative to the pump wavelength. The laser has a low lasing threshold for a Raman laser of 0.55 W, a peak slope efficiency of 14 %, and a maximum average output of 0.25 W. An investigation of beating between pure Raman and Raman-pumped Brillouin lasing shows that the outputs of the two processes are highly correlated and thus the Brillouin lasing is essentially single-frequency when CW and near transform limited for pulsed operation. A phenomenological model of the Raman-Brillouin interaction shows that the pulsing behaviour of such a cavity is expected and produces very similar pulsing to that the seen in experimental results.

The role of statins in the prevention of preeclampsia.

Preeclampsia is a common hypertensive disorder of pregnancy associated with considerable neonatal and maternal morbidities and mortalities. However, the exact cause of preeclampsia remains unknown; it is generally accepted that abnormal placentation resulting in the release of soluble antiangiogenic factors, coupled with increased oxidative stress and inflammation, leads to systemic endothelial dysfunction and the clinical manifestations of the disease. Statins have been found to correct similar pathophysiological pathways that underlie the development of preeclampsia. Pravastatin, specifically, has been reported in various preclinical and clinical studies to reverse the pregnancy-specific angiogenic imbalance associated with preeclampsia, to restore global endothelial health, and to prevent oxidative and inflammatory injury. Human studies have found a favorable safety profile for pravastatin, and more recent evidence does not support the previous teratogenic concerns surrounding statins in pregnancy. With reassuring and positive findings from pilot studies and strong biological plausibility, statins should be investigated in large clinical randomized-controlled trials for the prevention of preeclampsia.

Evaluation of classification methods for identifying multiwalled carbon nanotubes collected on mixed cellulose ester filter media.

Enhanced darkfield microscopy (EDFM) and hyperspectral imaging (HSI) are being evaluated as a potential rapid screening modality to reduce the time-to-knowledge for direct visualisation and analysis of filter media used to sample nanoparticulate from work environments, as compared to the current analytical gold standard of transmission electron microscopy (TEM). Here, we compare accuracy, specificity, and sensitivity of several hyperspectral classification models and data preprocessing techniques to determine how to most effectively identify multiwalled carbon nanotubes (MWCNTs) in hyperspectral images. Several classification schemes were identified that are capable of classifying pixels as MWCNT(+) or MWCNT(-) in hyperspectral images with specificity and sensitivity over 99% on the test dataset. Functional principal component analysis (FPCA) was identified as an appropriate data preprocessing technique, testing optimally when coupled with a quadratic discriminant analysis (QDA) model with forward stepwise variable selection and with a support vector machines (SVM) model. The success of these methods suggests that EDFM-HSI may be reliably employed to assess filter media exposed to MWCNTs. Future work will evaluate the ability of EDFM-HSI to quantify MWCNTs collected on filter media using this classification algorithm framework using the best-performing model identified here - quadratic discriminant analysis with forward stepwise selection on functional principal component data - on an expanded sample set.

The Importance of Clinical Presentation in Risk and Management of Recurrent Preterm Birth.

OBJECTIVE: This study aimed to compare the risk of recurrent spontaneous preterm birth (sPTB), as well as cerclage efficacy, between groups stratified by phenotype of the index sPTB. STUDY DESIGN: This is a retrospective cohort study of women with a history of sPTB. Included were women with a history of singleton sPTB who received progesterone in a subsequent pregnancy. Multifetal gestations and abdominal cerclage were excluded. Exposure groups were based upon the presenting symptom that preceded their first sPTB and included painless cervical dilation (PCD), preterm premature rupture of membranes (PPROM), and painful dilation (preterm labor [PTL]). Primary outcome was delivery <34 weeks in a subsequent pregnancy. Secondary outcomes included delivery <28 and <37 weeks. Rates were compared using the Chi-square test. Multivariable Poisson regression was used to adjust for confounders. RESULTS: A total of 723 women were included. A total of 114 (16%) presented with PCD, 305 (42%) with PPROM, and 304 (42%) with PTL in their first sPTB. Cerclage in subsequent pregnancy was highest in the PCD group (42%) when compared with the PPROM (16%) and PTL (12%) groups. Rates of sPTB <34 and 37 weeks were similar among the groups. After adjusting for confounders, PCD was found to significantly increase the risk of recurrent sPTB <28 weeks (incidence rate ratio: 3.46 [1.09-11.0]; p = 0.04). Of the 121 women who underwent cerclage, there were no significant differences in rates of sPTB between the clinical presentation groups. CONCLUSION: PCD as a specific phenotype of sPTB impacts recurrence of delivery before 28 weeks, but not at later gestational ages. In contrast, there was no significant association between clinical presentation of index sPTB and gestational latency in women who also underwent cerclage placement in a subsequent pregnancy. Our data suggest that clinical presentation is important with regards to recurrence of early sPTB, but not sPTB at later gestational ages. KEY POINTS: · Phenotype is critical to understanding PTB.. · Phenotype is associated with recurrent PTB.. · Painless dilation is associated with recurrent PTB..

Highly-chirped Bragg gratings for integrated silica spectrometers.

A blazed chirped Bragg grating in a planar silica waveguide device was used to create an integrated diffractive element for a spectrometer. The grating diffracts light from a waveguide and creates a wavelength dependent focus in a manner similar to a bulk diffraction grating spectrometer. An external imaging system is used to analyse the light, later device iterations plan to integrate detectors to make a fully integrated spectrometer. Devices were fabricated with grating period chirp rates in excess of 100 nm mm-1, achieving a focal length of 5.5 mm. Correction of coma aberrations resulted in a device with a footprint of 20 mm×10 mm, a peak FWHM resolution of 1.8 nm, a typical FWHM resolution of 2.6 nm and operating with a 160 nm bandwidth centered at 1550 nm.

Individual inscription of spectrally multiplexed Bragg gratings in optical multicore fibers using small spot direct UV writing.

We have demonstrated the inscription of Bragg gratings into five individual cores of a seven core fiber using small spot direct UV writing. With this technique, we defined spectrally multiplexed Bragg gratings consecutively in separate cores as well as spectrally multiplexed gratings at the same longitudinal location in different cores. The effect of bending on the optical spectrum was evaluated to allow the differentiation between cross-exposure and cross-talk, and an alignment process to reduce cross-exposure by 13 dB was found.

Intrahepatic Cholestasis of Pregnancy.

Intrahepatic cholestasis of pregnancy is a common disorder of pregnancy manifested by pruritus and elevated bile acids. The etiology of cholestasis is poorly understood and management is difficult due to the paucity of data regarding its diagnosis, treatment, and related adverse outcomes. In this article, we review the epidemiology, pathophysiology, risk factors, laboratory findings, complications, treatment, management, and current evidence surrounding intrahepatic cholestasis of pregnancy.

Exclusion of Pregnant Women from Clinical Trials during the Coronavirus Disease 2019 Pandemic: A Review of International Registries.

OBJECTIVE: Pregnant women have been historically excluded from clinical trials for nonobstetric conditions, even during prior epidemics. The objective of this review is to describe the current state of research for pregnant women during the coronavirus disease 2019 (COVID-19) pandemic. STUDY DESIGN: We conducted a search of international trial registries for trials relating to the novel coronavirus. The eligibility criteria for each trial were reviewed for inclusion/exclusion of pregnant women. Relevant data were extracted and descriptive statistics were calculated for individual and combined data. The total number of trials from each registry were compared, as well as the proportions of pregnancy-related trials within each. RESULTS: Among 621,370 trials in the World Health Organization International Clinical Trials Registry, 927 (0.15%) were COVID-19 related. Of those, the majority (52%) explicitly excluded pregnancy or failed to address pregnancy at all (46%) and only 16 (1.7%) were pregnancy specific. When categorized by region, 688 (74.2%) of COVID-19 trials were in Asia, followed by 128 (13.8%) in Europe, and 66 (7.2%) in North America. Of the COVID-19 trials which included pregnant women, only three were randomized-controlled drug trials. CONCLUSION: Approximately 1.7% of current COVID-19 research is pregnancy related and the majority of trials either explicitly exclude or fail to address pregnancy. Only three interventional trials worldwide involved pregnant women. The knowledge gap concerning the safety and efficacy of interventions for COVID-19 created by the exclusion of pregnant women may ultimately harm them. While "ethical" concerns about fetal exposure are often cited, it is in fact unethical to habitually exclude pregnant women from research. KEY POINTS: · Pregnancy was excluded from past pandemic research.. · Pregnancy is being excluded from COVID-19 research.. · Exclusion of pregnant women is potentially harmful..

Interspecies Bombolitins Exhibit Structural Diversity upon Membrane Binding, Leading to Cell Specificity.

Bombolitins, a class of peptides produced by bees of the genus Bombus, target and disrupt cellular membranes, leading to lysis. Antimicrobial peptides exhibit various mechanisms of action resulting from the interplay between peptide structure, lipid composition, and cellular target membrane selectivity. Herein, two bombolitins displaying significant amino-acid-sequence similarity, BII and BL6, were assessed for antimicrobial activity as well as correlated dodecylphosphocholine (DPC) micelle binding and membrane-induced peptide conformational changes. Infrared and circular dichroism spectroscopies were used to assess the structure-function relationship of each bombolitin, and the results indicate that BII forms a rigid and helically ordered secondary structure upon binding to DPC micelles, whereas BL6 largely lacks secondary structural order. Moreover, the binding affinity of each peptide to DPC micelles was determined, revealing that BL6 displayed a difference in binding affinity by over two orders of magnitude. Further investigations into the growth-inhibitory activity of the two bombolitins were performed against Escherichia coli and Saccharomyces cerevisiae. Interestingly, BII specifically targeted S. cerevisiae, whereas BL6 more effectively inhibited E. coli growth. Overall, the antimicrobial selectivity and specificity of BII and BL6 are largely dependent on the primary as well as secondary structural content of the peptides and the membrane composition.

A Putative Protein O-Fucosyltransferase Facilitates Pollen Tube Penetration through the Stigma-Style Interface.

During pollen-pistil interactions in angiosperms, the male gametophyte (pollen) germinates to produce a pollen tube. To fertilize ovules located within the female pistil, the pollen tube must physically penetrate specialized tissues. Whereas the process of pollen tube penetration through the pistil has been anatomically well described, the genetic regulation remains poorly understood. In this study, we identify a novel Arabidopsis (Arabidopsis thaliana) gene, O-FUCOSYLTRANSFERASE1 (AtOFT1), which plays a key role in pollen tube penetration through the stigma-style interface. Semi-in vivo growth assays demonstrate that oft1 mutant pollen tubes have a reduced ability to penetrate the stigma-style interface, leading to a nearly 2,000-fold decrease in oft1 pollen transmission efficiency and a 5- to 10-fold decreased seed set. We also demonstrate that AtOFT1 is localized to the Golgi apparatus, indicating its potential role in cellular glycosylation events. Finally, we demonstrate that AtOFT1 and other similar Arabidopsis genes represent a novel clade of sequences related to metazoan protein O-fucosyltransferases and that mutation of residues that are important for O-fucosyltransferase activity compromises AtOFT1 function in vivo. The results of this study elucidate a physiological function for AtOFT1 in pollen tube penetration through the stigma-style interface and highlight the potential importance of protein O-glycosylation events in pollen-pistil interactions.

Integrated polarizer based on 45° tilted gratings.

We report the first integrated implementation of a polarizer based on the use of 45° tilted gratings in planar waveguides. The waveguides and gratings are fabricated by direct UV writing in a hydrogenated germanium-doped silica-on-silicon chip. We experimentally demonstrate a polarization extinction ratio per unit length of 0.25 dB mm -1 with a modelled wavelength dependence smaller than 0.3 dB for a 20 mm device over the C band from 1530-1570 nm. We also present a novel numerical study and analytical description of the architecture that are in good agreement with each other and the experimental data.

Thermal approach to classifying sequentially written fiber Bragg gratings.

We demonstrate thermal classification of sequentially written fiber Bragg gratings. This Letter presents a process to determine the type of fiber Bragg grating written in SMF28 and GF4A by introducing the gratings to thermal treatment. This technique can be applied to several approaches based on sequential writing, including the small spot direct ultraviolet writing technique. Four different types of gratings have been identified, which are dependent on the fiber type and fluence used during the writing process.

Obesity and laboratory aspirin resistance in high-risk pregnant women treated with low-dose aspirin.

BACKGROUND: Low-dose aspirin is used for preeclampsia prevention in high-risk women, but the precise mechanism and optimal dose are unknown. Evidence suggests that an imbalance in prostacyclin and thromboxane A2 (TXA2) plays a key role in the pathogenesis of preeclampsia. Aspirin has a dose-dependent effect blocking production of TXA2, a potent stimulator of platelet aggregation and promoter of vasoconstriction. Incomplete inhibition of platelet aggregation, designated aspirin resistance, can be reduced by increasing the aspirin dose. Evidence in the nonobstetric literature suggests that aspirin resistance may be more common among patients with a high body mass index. OBJECTIVE: To investigate the association of obesity on platelet-derived thromboxane inhibition in high-risk women treated with low-dose aspirin. MATERIALS AND METHODS: This was a secondary analysis of a prospective multi-centered study investigating the effect of low-dose aspirin (60-mg) administration in women at high risk for preeclampsia. Maternal serum TXB2 (an indirect measure of TxA2) levels were drawn at 3 time points: randomization (13-26 weeks' gestation), second trimester (at least 2 weeks after randomization and 24-28 weeks' gestation), and third trimester (34-38 weeks' gestation). Patients were included in the analysis if a TXB2 level was recorded at randomization and at least 1 time point thereafter. Patients were stratified by body mass index category and treatment arm. Median TXB2 levels were calculated at each time point, as well as rates of complete TXB2 inhibition (<0.01 ng/mL). A multivariate logistic regression analysis was performed to generate odds ratios (OR) for complete TXB2 inhibition by body mass index category, adjusting for maternal age, race, high-risk group at randomization, nulliparity, and rate of randomization less than 16 weeks' gestation. RESULTS: A total of 1002 patients were included in the analysis, 496 (49.5%) and 506 (50.5%) in the low-dose aspirin and placebo groups respectively. There were substantial decreases in TXB2 levels among low-dose aspirin-treated women in all body mass index categories. In contrast, women assigned to placebo did not show a marked decrease in TXB2 levels after randomization, and obese women had higher median TXB2 levels in both the second (16.5, interquartile range [IQR] 8.0-31.8 vs 14.0, IQR 6.9-26.7, ng/mL; P = .032) and third (15.7, IQR 7.6-28.5 vs 11.9, IQR 4.6-25.9, ng/mL; P = .043) trimesters. When comparing among stratified body mass index low-dose aspirin groups, women with class III obesity had the lowest odds of undetectable TXB2 levels in the second trimester (adjusted odds ratio [aOR], 0.33; 95% confidence interval [CI], 0.15-0.72) and third trimester (aOR, 0.30; 95% CI, 0.11-0.78) as well as at both time points (aOR, 0.09; 95% CI, 0.02-0.41). CONCLUSION: High-risk obese women receiving low-dose aspirin for the prevention of preeclampsia have lower rates of complete inhibition of TXB2. These data suggest that an increase in aspirin dosing or frequency may be necessary in this population.

Cost Analysis of Azithromycin versus Erythromycin in Pregnancies Complicated by Preterm Premature Rupture of Membranes.

OBJECTIVE: To quantify the potential cost savings if azithromycin is substituted for erythromycin in women with preterm premature rupture of membranes (PPROM). STUDY DESIGN: Secondary analysis of a multicentered study investigating magnesium sulfate for the prevention of cerebral palsy in premature infants. All patients with PPROM who received antibiotics for prophylaxis were included in the analysis. The number of expected doses each patient would have received was calculated for erythromycin, multidose azithromycin, and single-dose azithromycin regimens accounting for latency from PPROM to delivery. The wholesale acquisition cost was used to calculate the expected cost of each regimen. RESULTS: There were 981 PPROM patients who received a penicillin class antibiotic and erythromycin. Patients would have received 7,528 intravenous doses and 10,194 oral doses of erythromycin at a combined cost of $357,169. In comparison, patients would have received 6,422 and 3,942 doses at a cost of $15,669 and $9,574 for the multidose and single-dose azithromycin regimens respectively, which represents a more than 95% cost reduction for either regimen compared with erythromycin. CONCLUSION: The use of azithromycin substituted for erythromycin in the standard antibiotic regimen of women with PPROM represents a potential for substantial cost reduction.

Leaky mode integrated optical fibre refractometer.

A route to monitor external refractive indices greater than the core index of the waveguide is presented. Initial application utilizes an integrated optical fibre (IOF) platform due to its potential for use in harsh environment sensing. IOF is fabricated using a bespoke flame hydrolysis deposition process to fuse an optical fibre to a planar substrate achieving an optical quality, ruggedized glass layer between the fibre and substrate was fabricated. The presented refractometer is created by direct UV writing of multiple fibre Bragg gratings into an etched (22 µm diameter) optical fibre post fabrication. Linear regression analysis is applied to quantify propagation loss by monitoring each FBG's back reflected power. The device operates with a sensitivity of approximately 350 dB/cm/RIU at a refractive index of 1.451 at 1550 nm. Numerical simulations using a transfer matrix method are presented and potential routes for development are discussed.

High-birefringence direct UV-written waveguides for use as heralded single-photon sources at telecommunication wavelengths.

Direct UV-written waveguides are fabricated in silica-on-silicon with birefringence of (4.9 ± 0.2) × 10-4, much greater than previously reported in this platform. We show that these waveguides are suitable for the generation of heralded single photons at telecommunication wavelengths by spontaneous four-wave mixing. A pulsed pump field at 1060 nm generates pairs of photons in highly detuned, spectrally uncorrelated modes near 1550 nm and 800 nm. Waveguide-to-fiber coupling efficiencies of 78-91 % are achieved for all fields. Waveguide birefringence is controlled through dopant concentration of GeCl4 and BCl3 using the flame hydrolysis deposition process. The technology provides a route towards the scalability of silica-on-silicon integrated components for photonic quantum experiments.

Effect of Maternal Age and Fetal Number on the Risk of Hypertensive Disorders of Pregnancy.

OBJECTIVE: Our primary objective was to compare the differential contribution of fetal number and maternal age to the risk of hypertensive disorders of pregnancy (HDP). STUDY DESIGN: This was a secondary analysis of a large study of primary cesarean delivery. Women with singleton, twin, or triplet gestations were included. Women were divided into groups based on fetal number and maternal age. The primary outcome was HDP. A logistic regression model was fit to adjust for confounders. The incidence of HDP was compared with the reference group and within exposure groups. RESULTS: Of the 70,417 women included, HDP occurred in 8,079 (12%) women. The frequency of HDP among the comparison groups ranged from 11 to 38%. Nearly all groups had significantly increased risk of HDP compared with young maternal age singletons. Twin and triplet gestations increased the risk of HDP over singletons irrespective of maternal age after adjusting for baseline disease and race. The risk of HDP did not significantly increase with maternal age when fetal number was similar. CONCLUSION: Fetal number significantly increased the risk of HDP and contributed more to that risk than maternal age. Maternal age became significant in groups with age greater than 40 years.

Mode of delivery at periviability and early childhood neurodevelopment.

OBJECTIVE: Little is known regarding the impact of mode of delivery in the periviable period. Even less is understood regarding the effect of mode of delivery on neurodevelopment. Our objective is to determine if the mode of delivery at time of periviability impacts Bayley II scores at 2 years of age. STUDY DESIGN: This is a secondary analysis of a randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy, a multicenter trial where women at imminent risk for delivery were assigned to receive magnesium sulfate or placebo. For this secondary analysis we included nonanomalous singleton gestations delivered between 23 4/7 and 25 6/7 weeks. We excluded women with missing exposure or outcome data. The primary exposure of interest was mode of delivery. The primary outcome was Bayley II scores <70 (mental and motor) at 2 years of age. Log binomial regression was used to control for possible confounders including gestational age at delivery, presentation at time of delivery, chorioamnionitis, years of maternal education, maternal body mass index, and original study treatment group. RESULTS: A total of 158 women met inclusion criteria. In all, 91 had a vaginal delivery and 67 had a cesarean delivery. Exposure to magnesium sulfate, maternal education, chorioamnionitis, years of maternal education, and maternal body mass index were similar in both groups. There was no difference in either mental or motor Bayley II scores <70 or <85 by mode of delivery in either univariable or multivariable analysis. CONCLUSION: There is no detectable difference in Bayley II scores between mode of delivery at time of periviability. This adds to the literature supporting obstetric indications dictating mode of delivery at this gestational age.