The variation and evolution of complete human centromeres.

Human centromeres have been traditionally very difficult to sequence and assemble owing to their repetitive nature and large size1. As a result, patterns of human centromeric variation and models for their evolution and function remain incomplete, despite centromeres being among the most rapidly mutating regions2,3. Here, using long-read sequencing, we completely sequenced and assembled all centromeres from a second human genome and compared it to the finished reference genome4,5. We find that the two sets of centromeres show at least a 4.1-fold increase in single-nucleotide variation when compared with their unique flanks and vary up to 3-fold in size. Moreover, we find that 45.8% of centromeric sequence cannot be reliably aligned using standard methods owing to the emergence of new α-satellite higher-order repeats (HORs). DNA methylation and CENP-A chromatin immunoprecipitation experiments show that 26% of the centromeres differ in their kinetochore position by >500 kb. To understand evolutionary change, we selected six chromosomes and sequenced and assembled 31 orthologous centromeres from the common chimpanzee, orangutan and macaque genomes. Comparative analyses reveal a nearly complete turnover of α-satellite HORs, with characteristic idiosyncratic changes in α-satellite HORs for each species. Phylogenetic reconstruction of human haplotypes supports limited to no recombination between the short (p) and long (q) arms across centromeres and reveals that novel α-satellite HORs share a monophyletic origin, providing a strategy to estimate the rate of saltatory amplification and mutation of human centromeric DNA.

Proton Sponge Zwitterions with Positively and Negatively Charged Hydrogen Bonds: Extremely Polar Organic Compounds and Interplay of [NHN]+ and [NHN]- Properties.

Six previously unknown zwitterions with positively and negatively charged [NHN] hydrogen bonds were synthesized by acylation of 4,5-bis(dimethylamino)-1-tosylamino-8-aminonaphthalene with subsequent alkaline treatment of the resulting 8-acylamino derivatives. Using NMR and XRD measurements in conjunction with quantum chemical DFT/PBE1PBE/6-311++G(d,p) calculations, it was shown that the negatively charged [NHN]- bond in such compounds commonly differs from the [NHN]+ bond by significantly lower linearity, higher asymmetry, and moderate to strong paramagnetic shift of the chelated NH proton signal. Among other remarkable findings, the most important are (1) unusually high polarity (µ = 21-26 D) of the obtained zwitterions, (2) sharp difference in structures of the solid 1,8-bis(tosylated) zwitterion (BTZ) grown from MeCN or DMF, and (3) registration for one of the stereoisomers of BTZ with the record short [NHN]- hydrogen bridge (N···N = 2.510 Å) almost reaching the theoretical limit (2.50 Å) for the [NHN]+ hydrogen bond.

The P300 wave is decomposed into components reflecting response selection and automatic reactivation of stimulus-response links.

The parietal P300 wave of event-related potentials (ERPs) has been associated with various psychological operations in numerous laboratory tasks. This study aims to decompose the P3 wave of ERPs into subcomponents and link them with behavioral parameters, such as the strength of stimulus-response (S-R) links and GO/NOGO responses. EEGs (31 channels), referenced to linked ears, were recorded from 172 healthy adults (107 women) who participated in two cued GO/NOGO tasks, where the strength of S-R links was manipulated through instructions. P300 waves were observed in active conditions in response to cues, GO/NOGO stimuli, and in passive conditions when no manual response was required. Utilizing a combination of current source density transformation and blind source separation methods, we decomposed the P300 wave into two distinct components, purportedly originating from different parts of the parietal lobules. The amplitude of the parietal midline component (with current sources around Pz) closely mirrored the strength of the S-R link across proactive, reactive, and passive conditions. The amplitude of the lateral parietal component (with current sources around P3 and P4) resembled the push-pull activity of the output nuclei of the basal ganglia in action selection-inhibition operations. These findings provide insights into the neural mechanisms underlying action selection processes and the reactivation of S-R links.

Light absorption by a planar array of spherical particles and a matrix in which they are embedded: statistical approach.

The fractions of light energy absorbed by a 2D array of spherical particles and the matrix in which they are embedded are determined. The solution is based on a volume integral equation and a statistical approach. The absorption coefficient of the array is found via the internal fields of the particles. The absorption coefficient of a matrix is found as the difference between the absorption coefficients of the composite structure and the particles. Numerical results are presented for arrays of metal, semiconductor, and dielectric nano- and microparticles of short-range order and imperfect long-range order in the absorbing media at normal and oblique incidence of a plane wave.

Neonatal Outcomes Are Similar between Patients with Resolved and Those with Persistent Oligohydramnios.

OBJECTIVE: Oligohydramnios (defined as amniotic fluid volume < 5 cm or deepest vertical pocket < 2 cm) is regarded as an ominous finding on prenatal ultrasound. Amniotic fluid, however, is not static, and to date, there have been no studies comparing perinatal outcomes in patients who are diagnosed with oligohydramnios that resolves and those who have persistent oligohydramnios. STUDY DESIGN: This is a secondary analysis of a National Institutes of Health-funded retrospective cohort study of singleton gestations delivered at a tertiary care hospital between 2002 and 2013 with mild hypertensive disorders and/or fetal growth restriction (FGR). Maternal characteristics, delivery, and neonatal information were abstracted by trained research nurses. Patients with a diagnosis of oligohydramnios were identified, and those with resolved versus persistent oligohydramnios at the time of delivery were compared. The primary outcome was a composite of neonatal resuscitation at delivery: administration of oxygen, bag-mask ventilation, continuous positive airway pressure, intubation, chest compression, or cardiac medication administration. Secondary outcomes included FGR, timing, and mode of delivery. RESULTS: Of 527 women meeting study criteria, 42 had oligohydramnios that resolved prior to delivery, whereas 485 had persistent oligohydramnios. There were no significant differences in patient demographics between groups. The gestational age at diagnosis was significantly lower for patients with resolved versus persistent oligohydramnios (median: 33.0 [interquartile range, IQR: 29.1-35.9] vs. 38.0 [IQR: 36.4-39.3], p < 0.001). There was not a substantial difference in rate of neonatal resuscitation (41 vs. 32%, p = 0.31). Patients with resolved oligohydramnios were more likely to have developed FGR than those with persistent oligohydramnios (55 vs. 36%, p < 0.02). There were no significant differences for gestational age at delivery, birth weight, or neonatal intensive care unit admission. CONCLUSION: Patients whose oligohydramnios resolved were diagnosed earlier yet had similar rates of neonatal resuscitation but higher rates of FGR than those who had persistent oligohydramnios. KEY POINTS: · When diagnosed earlier in pregnancy, oligohydramnios was more likely to resolve prenatally.. · Patients who were diagnosed with oligohydramnios earlier in pregnancy had higher rates of FGR.. · There were no differences in the rates of the composite outcome of need for neonatal resuscitation when comparing those with resolved versus those with persistent oligohydramnios. No differences in composite neonatal morbidity were noted between those with resolved versus persistent oligohydramnios..

Characterization of Secondary Metabolites of Leaf Buds from Some Species and Hybrids of Populus by Gas Chromatography Coupled with Mass Detection and Two-Dimensional High-Performance Thin-Layer Chromatography Methods with Assessment of Their Antioxidant Activity.

Poplars provide medicinal raw plant materials used in pharmacy. Leaf buds are one of the herbal medicinal products collected from poplars, having anti-inflammatory and antiseptic properties, but there are no quality standards for their production and there is a need to determine their botanical sources. Therefore, the chemical compositions of the leaf buds from four species and varieties of poplars, Populus balsamifera, P. × berolinensis, P. × canadensis 'Marilandica', and P. wilsonii were investigated and compared using gas chromatography coupled with mass detection (GC-MS) and two-dimensional high-performance thin-layer chromatography (2D-HPTLC) in order to search for taxa characterized by a high content of biologically active compounds and with a diverse chemical composition that determines their therapeutic effects. The presence of 163 compounds belonging to the groups of flavonoids, phenolic acids derivatives, glycerides, and sesquiterpenes was revealed. Moreover, the conditions for the separation and identification of biologically active compounds occurring in analyzed leaf buds using 2D-HPTLC were optimized and used for metabolomic profiling of the studied poplars, enabling their fast and simple botanical identification. The total phenolic (TPC) and flavonoid (TFC) contents of examined extracts were determined and their antioxidant capacities were estimated by spectrophotometric DPPH, ABTS, and FRAP assays. Based on the analysis of phytochemicals and antioxidant activity, P. × berolinensis buds were selected as the raw plant material for medicinal purposes with the highest content of active compounds and the strongest antioxidant activity.

Chemical Composition of Volatile and Extractive Components of Canary (Tenerife) Propolis.

The vegetation of the Canary Islands is characterized by a large number of endemic species confined to different altitudinal levels. It can be assumed that these circumstances determine the characteristic features of the chemical composition of local beekeeping products, including propolis. We report, for the first time, the chemical composition of propolis from Tenerife (Canary Islands). The volatile emissions of three propolis samples collected from different apiaries are represented by 162 C1-C20 compounds, of which 144 were identified using the HS-SPME/GC-MS technique. The main group of volatiles, consisting of 72 compounds, is formed by terpenoids, which account for 42-68% of the total ion current (TIC) of the chromatograms. The next most numerous groups are formed by C6-C17 alkanes and alkenes (6-32% TIC) and aliphatic C3-C11 carbonyl compounds (7-20% TIC). The volatile emissions also contain C1-C6 aliphatic acids and C2-C8 alcohols, as well as their esters. Peaks of 138 organic C3-C34 compounds were recorded in the chromatograms of the ether extracts of the studied propolis. Terpene compounds form the most numerous group, but their number and content in different samples is within very wide limits (9-63% TIC), which is probably due to the origin of the samples from apiaries located at different altitudes. A peculiarity of the chemical composition of the extractive substances is the almost complete absence of phenylcarboxylic acids and flavonoids, characteristic of Apis mellifera propolis from different regions of Eurasia and North America. Aromatic compounds of propolis from Tenerife are represented by a group of nine isomeric furofuranoid lignans, as well as alkyl- and alkenyl-substituted derivatives of salicylic acid and resorcinol.

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination.

The possibility of functionalization of dipyrido[3,2-e:2',3'-h]acenaphthene containing a quino[7,8-h]quinoline fragment and being a highly basic diazine analog of 1,8-bis(dimethylamino)naphthalene ("proton sponge") has been studied for the first time. In addition to the pronounced tendency of the title compound to form associates with an intramolecular hydrogen bond of the NHN type (new examples with the participation of pyridine rings, including self-associates are shown) and its inertness to amination reactions of the pyridine rings, the naphthalene core at positions 5(8) and the CH2CH2 bridge (dehydrogenation) undergo chemical modifications under mild conditions, giving the corresponding acenaphthylenes. The latter can also be obtained in an unusual way by tele-elimination from 5,8-dibromodipyridoacenaphthene by reaction with neutral or anionic bases.

New Nabokoite-like Phases ACu7 TeO4 (SO4 )5 Cl (A=Na, K, Rb, Cs) with Decorated and Distorted Square Kagome Lattices.

A new family of compounds ACu7 TeO4 (SO4 )5 Cl (A=Na, K, Rb, Cs) isostructural to mineral Nabokoite (K species) was synthesized by solid state and gas transport reactions in sealed ampoules and characterized in measurements of magnetization and specific heat in a wide temperature range. These complex compounds are of the utmost interest as a testing playground to study the properties of quasi-two-dimensional magnets with a square kagome lattice geometry. A quantum ground state of such a corner-sharing network is a spin liquid. Unlike idealized grid analyzed in numerous models, the square kagome lattice in nabokoites is wavy and distorted being composed of versatile triangles. Moreover, it contains "excessive" decorating magnetic ions, which makes magnetism of these objects even more complicated. The interaction of these decorating ions through virtual excitations of the square kagome lattice is accompanied by the formation of a long-range magnetic order coexisting with the spin liquid.

Predicting primary cesarean delivery in pregnancies complicated by gestational diabetes mellitus.

BACKGROUND: Prediction models have shown promise in helping clinicians and patients engage in shared decision-making by providing quantitative estimates of individual risk of important clinical outcomes. Gestational diabetes mellitus is a common complication of pregnancy, which places patients at higher risk of primary CD. Suspected fetal macrosomia diagnosed on prenatal ultrasound is a well-known risk factor for primary CD in patients with gestational diabetes mellitus, but tools incorporating multiple risk factors to provide more accurate CD risk are lacking. Such tools could help facilitate shared decision-making and risk reduction by identifying patients with both high and low chances of intrapartum primary CD. OBJECTIVE: This study aimed to develop and internally validate a multivariable model to estimate the risk of intrapartum primary CD in pregnancies complicated by gestational diabetes mellitus undergoing a trial of labor. STUDY DESIGN: This study identified a cohort of patients with gestational diabetes mellitus derived from a large, National Institutes of Health-funded medical record abstraction study who delivered singleton live-born infants at ≥34 weeks of gestation at a large tertiary care center between January 2002 and March 2013. The exclusion criteria included previous CD, contraindications to vaginal delivery, scheduled primary CD, and known fetal anomalies. Candidate predictors were clinical variables routinely available to a practitioner in the third trimester of pregnancy found to be associated with an increased risk of CD in gestational diabetes mellitus. Stepwise backward elimination was used to build the logistic regression model. The Hosmer-Lemeshow test was used to demonstrate goodness of fit. Model discrimination was evaluated via the concordance index and displayed as the area under the receiver operating characteristic curve. Internal model validation was performed with bootstrapping of the original dataset. Random resampling with replacement was performed for 1000 replications to assess predictive ability. An additional analysis was performed in which the population was stratified by parity to evaluate the model's predictive ability among nulliparous and multiparous individuals. RESULTS: Of the 3570 pregnancies meeting the study criteria, 987 (28%) had a primary CD. Of note, 8 variables were included in the final model, all significantly associated with CD. They included large for gestational age, polyhydramnios, older maternal age, early pregnancy body mass index, first hemoglobin A1C recorded in pregnancy, nulliparity, insulin treatment, and preeclampsia. Model calibration and discrimination were satisfactory with the Hosmer-Lemeshow test (P=.862) and an area under the receiver operating characteristic curve of 0.75 (95% confidence interval, 0.74-0.77). Internal validation demonstrated similar discriminatory ability. Stratification by parity demonstrated that the model worked well among both nulliparous and multiparous patients. CONCLUSION: Using information routinely available in the third trimester of pregnancy, a clinically pragmatic model can predict intrapartum primary CD risk with reasonable reliability in pregnancies complicated by gestational diabetes mellitus and may provide quantitative data to guide patients in understanding their individual primary CD risk based on preexisting and acquired risk factors.

Synthesis, conformational stability and molecular structure of 4-aryl- and 4,5-diaryl-1,8-bis(dimethylamino)naphthalenes.

4-Bromo- and 4,5-dibromo-1,8-bis(dimethylamino)naphthalenes were arylated with arylboronic acids under Suzuki reaction conditions to provide 4-aryl- and 4,5-diaryl-1,8-bis(dimethylamino)naphthalenes, respectively. The interaction of 4,5-dibromo-1,8-bis(dimethylamino)naphthalene with pyridin-3-ylboronic acid was accompanied by heterocyclization leading unexpectedly to the formation of N3,N3,N4,N4-tetramethylacenaphtho[1,2-b]pyridine-3,4-diamine. Dynamic 1H NMR experiments showed fast interconversion between syn and anti conformers of 4,5-diaryl-1,8-bis(dimethylamino)naphthalenes in CDCl3 solution at room temperature. The free energy of the rotational isomerization was determined to be ∼14.0 kcal mol-1 for 4,5-di(m-tolyl) and 4,5-di(naphthalen-2-yl) derivatives. X-ray analysis of 4,5-diaryl-1,8-bis(dimethylamino)naphthalenes revealed a high degree of structural deformation due to internal steric repulsions between both peri-dimethylamino and peri-aryl groups. In crystals, 4,5-di(naphthalen-1-yl)-1,8-bis(dimethylamino)naphthalene molecules exist exclusively in the most stable anti-out form, while for 4,5-di(naphthalen-2-yl) and 4,5-di(m-tolyl) counterparts, only the syn-form is realized. The introduction of two peri-aryl substituents in the 1,8-bis(dimethylamino)naphthalene scaffold affected the basic properties, making the 4,5-diphenyl derivative 0.7 pKa units less basic. The protonation of 4,5-diaryl-1,8-bis(dimethylamino)naphthalenes leads to dramatic changes in their structures. Compared to the corresponding bases, the inter-nitrogen distance in these salts noticeably decreases whereas peri-aromatic rings move away from each other demonstrating the so-called "clothespin effect". This lowers the barriers of syn/anti-isomerization; as a result, protonated molecules with peri-m-tolyl and even peri-(naphthalen-2-yl) substituents exist in crystals as mixtures of rotamers.

Second Order Blind Identification of Event Related Potentials Sources.

Event-related potentials (ERPs) recorded on the surface of the head are a mixture of signals from many sources in the brain due to volume conductions. As a result, the spatial resolution of the ERPs is quite low. Blind source separation can help to recover source signals from multichannel ERP records. In this study, we present a novel implementation of a method for decomposing multi-channel ERP into components, which is based on the modeling of second-order statistics of ERPs. We also report a new implementation of Bayesian Information Criteria (BIC), which is used to select the optimal number of hidden signals (components) in the original ERPs. We tested these methods using both synthetic datasets and real ERPs data arrays. Testing has shown that the ERP decomposition method can reconstruct the source signals from their mixture with acceptable accuracy even when these signals overlap significantly in time and the presence of noise. The use of BIC allows us to determine the correct number of source signals at the signal-to-noise ratio commonly observed in ERP studies. The proposed approach was compared with conventionally used methods for the analysis of ERPs. It turned out that the use of this new method makes it possible to observe such phenomena that are hidden by other signals in the original ERPs. The proposed method for decomposing a multichannel ERP into components can be useful for studying cognitive processes in laboratory settings, as well as in clinical studies.

Unraveling the low-temperature activity of Rh-CeO2 catalysts in CO oxidation: probing the local structure and Red-Ox transformation of Rh3+ species.

The local structure of the active sites is one of the key aspects of establishing the nature of the catalytic activity of the systems. In this work, a detailed structural investigation of the Rh-CeO2 catalysts prepared by the co-precipitation method was carried out. The application of a variety of physicochemical methods such as XRD, Raman spectroscopy, XPS, TEM, TPR-H2, and XAS revealed the presence of highly dispersed Rh3+ species in the catalysts: Rh3+ single ions and RhOx clusters. The substitution of Ce4+ ions by Rh3+ species, which provided a strong distortion of the CeO2 lattice, is shown. XAS data ensured the refinement of the Rh local structure. It was shown that single Rh3+ sites located next to each other can merge the formation of RhOx clusters with Rh local environment close to the one in Rh2O3 and CeRh2O5 oxides. The distortion of the CeO2 lattice around single and cluster rhodium species had a beneficial effect on the catalytic activity of the samples in low-temperature CO oxidation (LTO-CO). TEM, XAS, and in situ XRD data allowed establishing the structural transformations of the catalysts under Red-Ox treatments. The reduction treatment led to Rhn metallic cluster formation localized on defects of the reduced CeO2-δ. The reduced sample demonstrated efficient CO conversion at 0 °C. However, this system was not stable: its contact with air led to ceria reoxidation and partial reoxidation of Rh to highly dispersed Rh3+ species at room temperature, while heating in an oxidizing atmosphere resulted in the complete reoxidation of metallic rhodium species. The results of the work shed light on the structural aspects of the reversibility of the Rh-CeO2 catalysts based on the highly dispersed Rh3+ species under treatment in the reaction conditions.

Frailty as a predictor of delayed initiation of adjuvant chemotherapy in patients with ovarian cancer.

OBJECTIVE: This study aimed to identify whether frailty is associated with the time between surgery and the initiation of chemotherapy for patients with ovarian cancer. METHODS: This retrospective cohort study included patients 18 years or older with stage II to IV ovarian cancer who underwent primary debulking surgery at a tertiary medical center between July 2006 and July 2015. Basic demographics and clinical information were obtained from a departmental database and the electronic medical record. The Modified Frailty Index (mFI) was calculated based on 10 comorbidities and functional status yielding 11 items total. Patients were categorized by a total score: 0-1=no frailty, 2=moderate frailty and 3+=high frailty. RESULTS: Among 451 patients, 359 had mFI scores of 0-1, 60 had a score of 2, and 32 had scores of 3+. Mean time from surgery to initiation of chemotherapy was 37 days. Mean number of days between surgery and initiation of chemotherapy increased with increasing frailty score: 36 days for the not frail group, 39 days for the moderate frailty group, and 54 days for the high frailty group (p<0.001). Time to initiation of chemotherapy of 42 days or more occurred in 23% of the no frailty group, 28% in the moderate frailty group, and 63% in the high frailty group (p<0.001). Overall survival decreased with increasing frailty scores. CONCLUSION: High mFI scores lead to a greater delay between surgery and chemotherapy initiation. Being able to predict delays in initiation of chemotherapy may allow oncologists to consider neoadjuvant chemotherapy, pre-habilitation before surgery, and improved preoperative counseling in high-risk patients.

Optical characteristics of a monolayer of identical spherical particles in an absorbing host medium.

The problem of light interaction with a 2D ensemble of homogeneous spherical particles embedded into an unbounded homogeneous absorbing host medium is considered. Based on the statistical approach, the equations are derived to characterize optical response of such a system with taking into account multiple scattering of light. Numerical data are presented for the spectral behavior of coherent transmission and reflection, incoherent scattering, and absorption coefficients of thin dielectric, semiconductor, and metal films containing a monolayer of particles with various spatial organization. The results are compared with the characteristics of the inverse structure: particles consist of the host medium material and vice versa. Data for the redshift of the surface plasmon resonance of the monolayer of gold (Au) nanoparticles in the fullerene (C 60) matrix are presented as a function of the monolayer filling factor. They are in qualitative agreement with the known experimental results. The findings have potential applications in the development of new electro-optical and photonic devices.

From "disappointing" to "fantastic": Women's experiences with labor induction in a U.S. tertiary hospital.

OBJECTIVE: The series of interventions that comprise labor induction shape patient experiences; however, patient perceptions are not always considered when structuring the process of care. Through qualitative interviews, we elucidated women's expectations and experiences regarding labor induction. METHODS: Labor induction patients were recruited from a United States tertiary care hospital's postpartum mother-baby unit and invited to participate in semi-structured qualitative interviews. Interview questions included expectations and experiences of the labor induction process, side effects and health outcomes of concern, reflections on personal tolerance of different interventions, and thoughts about an ideal process. RESULTS: Between April and September 2018, 36 women were interviewed. The labor induction process involved a wide range of experiences; when asked to characterize labor induction in one word, responses ranged from horrible, frustrating, and terrifying to simple, fast, and smooth. Inductions were often described as longer than what was expected. The most polarizing induction method was the Foley balloon catheter. Women's concerns regarding side effects largely centered on the health of their baby, and an ideal induction involved fewer interventions. CONCLUSIONS: Experiences with labor induction vary greatly and are related to expectations. The way interventions are introduced influences women's perceptions of control and their ultimate level of contentment with the birthing process. Attention to experiences and preferences has the potential to improve quality of care through communication, shared decision-making, and education.

Outcomes among Neonates after a Diagnosis of Persistent or Transient Fetal Growth Restriction Delivered at Term.

OBJECTIVE: This study aimed to evaluate whether transient fetal growth restriction (FGR) that resolves prior to delivery confers a similar risk of neonatal morbidity as uncomplicated FGR that persists at term. STUDY DESIGN: This is a secondary analysis of a medical record abstraction study of singleton live-born pregnancies delivered at a tertiary care center between 2002 and 2013. Patients with fetuses that had either persistent or transient FGR and delivered at 38 weeks or later were included. Patients with abnormal umbilical artery Doppler studies were excluded. Persistent FGR was defined as estimated fetal weight (EFW) <10th percentile by gestational age from diagnosis through delivery. Transient FGR was defined as EFW <10th percentile on at least one ultrasound, but not on the last ultrasound prior to delivery. The primary outcome was a composite of neonatal morbidity: neonatal intensive care unit admission, Apgar's score <7 at 5 minutes, neonatal resuscitation, arterial cord pH <7.1, respiratory distress syndrome, transient tachypnea of the newborn, hypoglycemia, sepsis, or death. Baseline characteristics and obstetric and neonatal outcomes were compared using Wilcoxon's rank-sum and Fisher's exact test. Log binomial regression was used to adjust for confounders. RESULTS: Of 777 patients studied, 686 (88%) had persistent FGR and 91 (12%) had transient FGR. Patients with transient FGR were more likely to have a higher body mass index, gestational diabetes, diagnosed with FGR earlier in pregnancy, have spontaneous labor, and deliver at later gestational ages. There was no difference in the composite neonatal outcome (relative risk = 1.03, 95% confidence interval [CI] 0.72, 1.47) for transient versus persistent FGR after adjusting for confounders (adjusted relative risk = 0.79, 95% CI 0.54, 1.17). There were no differences in cesarean delivery or delivery complications between groups. CONCLUSION: Neonates born at term after transient FGR do not appear to have differences in composite morbidity compared with those where uncomplicated FGR persists at term. KEY POINTS: · No differences in neonatal outcomes in uncomplicated persistent versus transient FGR at term.. · Transient FGR pregnancies more likely to deliver at later gestational ages.. · No differences in mode of delivery or obstetric complications in persistent versus transient FGR at term..

Prediction Model Assessing Risk of Delivery after Diagnosis of Abnormal Umbilical Artery Doppler.

OBJECTIVE: Umbilical artery Doppler (UAD) velocimetry abnormalities are associated with increased neonatal morbidity and mortality. Currently, there are no risk stratification methods to assist in antepartum management such as timing of antenatal corticosteroids (ACS). Therefore, we sought to develop a model to predict risk of delivery within 7 days following diagnosis of abnormal UAD velocimetry in patients with fetal growth restriction (FGR). STUDY DESIGN: Retrospective single referral center study of liveborn singleton pregnancies complicated by FGR and ≥1 abnormal UAD velocimetry value (≥95th percentile for gestational age [GA]). We considered 17 variables and used backward stepwise logistic regression to create a multivariable model for the prediction of delivery within 7 days. We assessed model fit with calibration, discrimination, likelihood ratios, and area under the curve. Internal validation of the model was assessed by using the bootstrap method. RESULTS: Between 2008 and 2015, a total of 176 patients were eligible and included for model development. Median (range) GA at initial eligibility was 32.1 weeks (28.1-36.1 weeks) and from initial eligibility until delivery was 21 days (0-104 days). Fifty-two patients (30%) were delivered in the 7 days following inclusion. GA at first abnormal UAD, severity of first abnormal UAD, oligohydramnios, preeclampsia, and pre-pregnancy BMI were included in the model. The model had an area under the ROC curve of 0.94 (95% confidence interval [CI]: 0.90-0.98), sensitivity of 85%, and specificity of 91%. If the model alone were used for ACS timing, 85% of the cohort who delivered in the following week would have received ACS, and ACS would not have been given to 91% who delivered later. Internal validation yielded similar results with a mean area under the curve (95% CI) of 0.94 (0.88-0.98). CONCLUSION: If validated externally, our model can be used to predict risk of delivery in patients with FGR and abnormal UAD velocimetry, potentially improving timing of ACS. KEY POINTS: · Risk of delivery in seven days can be predicted.. · Risk of delivery can inform corticosteroid timing.. · External validation can further develop a clinical aid..

Neonatal and Maternal Outcomes of Pregnancies following Stillbirth.

OBJECTIVE: Prior stillbirth increases risk of subsequent stillbirth but has unclear effect on subsequent liveborn pregnancies. We examined associations between prior stillbirth, adverse neonatal outcomes, and maternal morbidity in subsequent liveborn pregnancies. STUDY DESIGN: This is a secondary analysis of a large, National Institutes of Health-funded retrospective cohort study of parturients who delivered a singleton infant at a tertiary-care hospital from January 2002 to March 2013 and had a past medical/obstetric history of diabetic, and/or hypertensive disorders, and/or pregnancy with fetal growth restriction. Our analysis included all multiparous patients from the parent study. The primary outcome was a neonatal morbidity composite (neonatal resuscitation, neonatal birth injury, respiratory distress syndrome, transient tachypnea of the newborn, hypoglycemia, sepsis). Secondary outcomes included a maternal morbidity composite (venous thromboembolism, intensive care unit admission, disseminated intravascular coagulation, sepsis, hysterectomy, pulmonary edema, renal failure, blood transfusion), other maternal/delivery complications, and neonatal intensive care unit (NICU) admission. Outcomes were compared between those with versus without prior stillbirth. Negative binomial regression controlled for maternal comorbidities and delivery year. RESULTS: Among 171 and 5,245 multiparous parturients with versus without prior stillbirth, respectively, those with prior stillbirth had higher rates of pregestational diabetes, autoimmune disease, and clotting disorders. After controlling for these differences and delivery year, infants of parturients with prior stillbirth had similar risk of composite neonatal morbidity (adjusted relative ratio [aRR] 1.19; 95% confidence interval [CI] 0.99-1.45) but higher risk of NICU admission (aRR 1.42; 95% CI 1.06-1.91) compared with infants of parturients without prior stillbirth, despite delivering at similar gestational ages. Multiparous patients with prior stillbirth had equal maternal morbidity risk but higher risk of developing preeclampsia with severe features (aRR 2.11; 95% CI 1.19-3.72). CONCLUSION: Compared with high-risk multiparous patients without prior stillbirth, those with prior stillbirth have higher risk of NICU admission and preeclampsia with severe features. KEY POINTS: · Prior stillbirth increases risk in subsequent livebirth for NICU admission and neonatal morbidity.. · Prior stillbirth increased the risk of severe preeclampsia for mothers in subsequent livebirth.. · Additional monitoring of pregnancies of patients with prior history of demise may be warranted..

Silicon-Vacancy Nanodiamonds as High Performance Near-Infrared Emitters for Live-Cell Dual-Color Imaging and Thermometry.

Nanodiamonds (NDs) with color centers are excellent emitters for various bioimaging and quantum biosensing applications. In our work, we explore new applications of NDs with silicon-vacancy centers (SiV) obtained by high-pressure high-temperature (HPHT) synthesis based on metal-catalyst-free growth. They are coated with a polypeptide biopolymer, which is essential for efficient cellular uptake. The unique optical properties of NDs with SiV are their high photostability and narrow emission in the near-infrared region. Our results demonstrate for the first time that NDs with SiV allow live-cell dual-color imaging and intracellular tracking. Also, intracellular thermometry and challenges associated with SiV atomic defects in NDs are investigated and discussed for the first time. NDs with SiV nanoemitters provide new avenues for live-cell bioimaging, diagnostic (SiV as a nanosized thermometer), and theranostic (nanodiamonds as drug carrier) applications.