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We perform a joint Bayesian inference of neutron-star mass and radius constraints based on GW170817, observations of quiescent low-mass x-ray binaries (QLMXBs), photospheric radius expansion x-ray bursting sources, and x-ray timing observations of J0030+0451. With this dataset, the form of the prior distribution still has an impact on the posterior mass-radius curves and equation of state (EOS), but this impact is smaller than recently obtained when considering QLMXBs alone. We analyze the consistency of the electromagnetic data by including an "intrinsic scattering" contribution to the uncertainties, and find only a slight broadening of the posteriors. This suggests that the gravitational-wave and electromagnetic observations of neutron-star structure are providing a consistent picture of the neutron-star mass-radius curve and the EOS.

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We use population inference to explore the impact that uncertainties in the distribution of binary black holes (BBH) have on the astrophysical gravitational-wave background (AGWB). Our results show that the AGWB monopole is sensitive to the nature of the BBH population (particularly the local merger rate), while the anisotropic C_{ℓ} spectrum is only modified to within a few percent, at a level which is insignificant compared to other sources of uncertainty (such as cosmic variance). This is very promising news for future observational studies of the AGWB, as it shows that (i) the monopole can be used as a new probe of the population of compact objects throughout cosmic history, complementary to direct observations by LIGO and Virgo and (ii) we are able to make surprisingly robust predictions for the C_{ℓ} spectrum, even with only very approximate knowledge of the black hole population. As a result, the AGWB anisotropies have enormous potential as a new probe of the large-scale structure of the Universe, and of late-Universe cosmology in general.

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OBJECTIVE: The aim of this study was to define the natural history of lower urinary tract obstruction (LUTO) with normal midgestational amniotic fluid volumes. MATERIALS AND METHODS: We performed a retrospective review of 32 consecutive patients with LUTO with normal midgestational amniotic fluid volume followed at 11 North American Fetal Therapy Network (NAFTNet) centers from August 2007 to May 2012. Normal amniotic fluid volume was defined as an amniotic fluid index (AFI) of ≥9 cm. RESULTS: The mean gestational age (GA) and AFI at enrollment were 23.1 ± 2.1 weeks and 15.8 ± 3.9 cm, respectively. The mean GA at delivery was 37.3 ± 2.8 weeks. The mean creatinine level at discharge was 1.2 ± 0.8 mg/dL. Perinatal survival was 97%. Twenty-five patients returned for serial postnatal assessment. Renal replacement therapy (RRT) was required in 32%. Development of oligohydramnios and/or anhydramnios, development of cortical renal cysts, posterior urethral valves, prematurity, and prolonged neonatal intensive care unit stay were associated with need for RRT (p < 0.05) by univariate analysis. By multivariate analysis, preterm delivery remained predictive of need for RRT (p = 0.004). CONCLUSION: Prenatal diagnosis of LUTO with normal midgestational amniotic fluid volumes is associated with acceptable renal function in the majority of patients. Approximately one-third of these children require RRT. Surrogate markers of disease severity appear to be predictive of need for RRT.

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The inferred parameters of the binary black hole GW151226 are consistent with nonzero spin for the most massive black hole, misaligned from the binary's orbital angular momentum. If the black holes formed through isolated binary evolution from an initially aligned binary star, this misalignment would then arise from a natal kick imparted to the first-born black hole at its birth during stellar collapse. We use simple kinematic arguments to constrain the characteristic magnitude of this kick, and find that a natal kick v_{k}≳50 km/s must be imparted to the black hole at birth to produce misalignments consistent with GW151226. Such large natal kicks exceed those adopted by default in most of the current supernova and binary evolution models.

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OBJECTIVE: To estimate the accuracy of a new assay to determine the fetal RHD status using circulating cell-free DNA. METHODS: This was a prospective, observational study. Maternal blood samples were collected in each trimester of pregnancy in 520 nonalloimmunized RhD-negative patients. Plasma samples were analyzed for circulating cell-free DNA using the SensiGENE RHD test, which used primers for exons 4 and 7 as previously described and incorporated a new primer design for exon 5 of the RHD gene. Neonatal serology for RhD typing using cord blood at birth was undertaken and results were stored in a separate clinical database. After unblinding the data, results of the DNA analysis were compared with the neonatal serology. RESULTS: Inconclusive results secondary to the presence of the RHD pseudogene or an RHD variant were noted in 5.6%, 5.7%, and 6.1% of the first-, second-, and third-trimester samples, respectively. The incidence of false-positive rates for RhD (an RhD-negative fetus with an RHD-positive result) was 1.54% (95% confidence interval [CI] 0.42-5.44%), 1.53% (CI 0.42-5.40%), and 0.82% (CI 0.04-4.50%), respectively. There was only one false-negative diagnosis (an RhD-positive fetus with an RHD-negative result), which occurred in the first trimester (0.32%; 95% CI 0.08-1.78%). Genotyping for mismatches across repeated samples revealed that this error was related to mislabeling of samples from two patients collected on the same day at one of the collection sites. Overall test results were in agreement across all three trimesters (P>.99). CONCLUSION: Circulating cell-free DNA can accurately predict the fetal RhD status in all three trimesters of pregnancy.

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The merger of two massive (about 30 solar masses) black holes has been detected in gravitational waves. This discovery validates recent predictions that massive binary black holes would constitute the first detection. Previous calculations, however, have not sampled the relevant binary-black-hole progenitors--massive, low-metallicity binary stars--with sufficient accuracy nor included sufficiently realistic physics to enable robust predictions to better than several orders of magnitude. Here we report high-precision numerical simulations of the formation of binary black holes via the evolution of isolated binary stars, providing a framework within which to interpret the first gravitational-wave source, GW150914, and to predict the properties of subsequent binary-black-hole gravitational-wave events. Our models imply that these events form in an environment in which the metallicity is less than ten per cent of solar metallicity, and involve stars with initial masses of 40-100 solar masses that interact through mass transfer and a common-envelope phase. These progenitor stars probably formed either about 2 billion years or, with a smaller probability, 11 billion years after the Big Bang. Most binary black holes form without supernova explosions, and their spins are nearly unchanged since birth, but do not have to be parallel. The classical field formation of binary black holes we propose, with low natal kicks (the velocity of the black hole at birth) and restricted common-envelope evolution, produces approximately 40 times more binary-black-holes mergers than do dynamical formation channels involving globular clusters; our predicted detection rate of these mergers is comparable to that from homogeneous evolution channels. Our calculations predict detections of about 1,000 black-hole mergers per year with total masses of 20-80 solar masses once second-generation ground-based gravitational-wave observatories reach full sensitivity.

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BACKGROUND: Stage I twin-twin transfusion syndrome presents a management dilemma. Intervention may lead to procedure-related complications while expectant management risks deterioration. Insufficient data exist to inform decision-making. OBJECTIVE: The aim of this retrospective observational study was to describe the natural history of stage I twin-twin transfusion syndrome, to assess for predictors of disease behavior, and to compare pregnancy outcomes after intervention at stage I vs expectant management. STUDY DESIGN: Ten North American Fetal Therapy Network centers submitted well-documented cases of stage I twin-twin transfusion syndrome for analysis. Cases were retrospectively divided into 3 management strategies: those managed expectantly, those who underwent amnioreduction at stage I, and those who underwent laser therapy at stage I. Outcomes were categorized as no survivors, 1 survivor, 2 survivors, or at least 1 survivor to live birth, and good (twin live birth ≥30.0 weeks), mixed (single fetal demise or delivery between 26.0-29.9 weeks), and poor (double fetal demise or delivery <26.0 weeks) pregnancy outcomes. Outcomes were analyzed by initial management strategy. RESULTS: A total of 124 cases of stage I twin-twin transfusion syndrome were studied. In all, 49 (40%) cases were managed expectantly while 30 (24%) underwent amnioreduction and 45 (36%) underwent laser therapy at stage I. The overall fetal mortality rate was 20.2% (50 of 248 fetuses). Of those managed expectantly, 11 patients regressed (22%), 4 remained stage I (8%), 29 advanced in stage (60%), and 5 experienced spontaneous previable preterm birth (10%) during observation. The mean number of days from diagnosis of stage I to a change in status (progression, regression, loss, or delivery) was 11.1 (SD 14.3) days. Intervention by amniocentesis or laser therapy was associated with a lower risk of fetal loss (P = .01) than expectant management. The unadjusted odds of poor outcome were 0.33 (95% confidence interval, 0.09-01.20), for amnioreduction and 0.26 (95% confidence interval, 0.09-0.77) for laser therapy vs expectant management. Adjusting for nulliparity, recipient maximum vertical pocket, gestational age at diagnosis, and placenta location had negligible effect. Both amnioreduction and laser therapy at stage I decreased the likelihood of no survivors (odds ratio, 0.11; 95% confidence interval, 0.02-0.68 and odds ratio, 0.07; 95% confidence interval, 0.01-0.37, respectively). Only laser therapy, however, was protective against poor outcome in our data (odds ratio, 0.29; 95% confidence interval, 0.07-1.30 for amnioreduction vs odds ratio, 0.12, 95% confidence interval, 0.03-0.44 for laser), although the estimate for amnioreduction suggests a protective effect. CONCLUSION: Stage I twin-twin transfusion syndrome was associated with substantial fetal mortality. Spontaneous resolution was observed, although the majority of expectantly managed cases progressed. Progression was associated with a worse prognosis. Both amnioreduction and laser therapy decreased the chance of no survivors, and laser was particularly protective against poor outcome independent of multiple factors. Further studies are justified to corroborate these findings and to further define risk stratification and surveillance strategies for stage I disease.

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Objectives The objective is to present a pregnancy complication associated with intravenous drug use, namely, that of red blood cell alloimmunization and hemolytic disease of the fetus and newborn. Methods An observational case series is presented including women with red blood cell alloimmunization most likely secondary to intravenous drug abuse Results Five pregnancies were identified that were complicated by red blood cell alloimmunization and significant hemolytic disease of the fetus and newborn, necessitating intrauterine transfusion, an indicated preterm birth, or neonatal therapy. Conclusions As opioid abuse continues to increase in the United States, clinicians should be aware of the potential for alloimmunization to red blood cell antibodies as yet another negative outcome from intravenous drug abuse.

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OBJECTIVE: The objective of this study is to describe the effects of antepartum therapy for fetal alloimmune thrombocytopenia (FAIT) on lifestyle. With the goal of preventing intraventricular hemorrhage in all fetuses without cordocentesis to measure fetal platelets, empiric treatment with intravenous immune globulin (IVIG), with or without prednisone, is recommended. It is hypothesized that these treatments negatively affect women's lifestyle. This information is needed for pre-conceptual counseling and developing management strategies. METHODS: A survey was mailed to 62 women treated by one provider from 2005 to 2013 asking if they experienced side effects from IVIG and prednisone, if their lives were negatively affected, if they would plan another affected pregnancy and if they needed help managing side effects. RESULTS: Three-quarters of 32 respondents reported that the treatments negatively affected their lifestyle. Thirty-one percent of women would not plan another pregnancy due to their experience and 22% were uncertain. All women experienced adverse effects and required additional medications or healthcare resources. Ninety-four percent contacted healthcare providers for help managing side effects. CONCLUSION: The significant negative effects on the lifestyle of women treated for FAIT emphasizes the need to identify the lowest effective doses and duration of pharmacotherapy and develop management strategies. Women undergoing treatment may need additional healthcare resources, including coordination of care.

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Binary black holes on quasicircular orbits with spins aligned with their orbital angular momentum have been test beds for analytic and numerical relativity for decades, not least because symmetry ensures that such configurations are equilibrium solutions to the spin-precession equations. In this work, we show that these solutions can be unstable when the spin of the higher-mass black hole is aligned with the orbital angular momentum and the spin of the lower-mass black hole is antialigned. Spins in these configurations are unstable to precession to large misalignment when the binary separation r is between the values r(ud±)=(√(χ(1))±âˆš(qχ(2)))(4)(1-q)(-2)M, where M is the total mass, q≡m(2)/m(1) is the mass ratio, and χ(1) (χ(2)) is the dimensionless spin of the more (less) massive black hole. This instability exists for a wide range of spin magnitudes and mass ratios and can occur in the strong-field regime near the merger. We describe the origin and nature of the instability using recently developed analytical techniques to characterize fully generic spin precession. This instability provides a channel to circumvent astrophysical spin alignment at large binary separations, allowing significant spin precession prior to merger affecting both gravitational-wave and electromagnetic signatures of stellar-mass and supermassive binary black holes.

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We derive an effective potential for binary black hole (BBH) spin precession at second post-Newtonian order. This effective potential allows us to solve the orbit-averaged spin-precession equations analytically for arbitrary mass ratios and spins. These solutions are quasiperiodic functions of time: after a fixed period, the BBH spins return to their initial relative orientations and jointly precess about the total angular momentum by a fixed angle. Using these solutions, we classify BBH spin precession into three distinct morphologies between which BBHs can transition during their inspiral. We also derive a precession-averaged evolution equation for the total angular momentum that can be integrated on the radiation-reaction time and identify a new class of spin-orbit resonances that can tilt the direction of the total angular momentum during the inspiral. Our new results will help efforts to model and interpret gravitational waves from generic BBH mergers and predict the distributions of final spins and gravitational recoils.

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OBJECTIVE: The objective of the study was to determine whether women with combinations of red blood cell antibodies are more likely to develop significant hemolytic disease of the fetus and newborn than those with single antibodies. STUDY DESIGN: A retrospective exposure cohort study was conducted of pregnant women with red blood cell antibodies. The development of significant hemolytic disease of the fetus and newborn was then compared between patients with single antibodies and those with multiple antibodies. Data analysis was limited to pregnancies delivering since the year 2000. RESULTS: Thirteen percent of the patients referred to our program had multiple red blood cell antibodies. Odds of developing significant hemolytic disease of the fetus and newborn for patients with anti-Rh(D) combined with at least 1 additional red blood cell antibody were 3.65 times the odds for women with anti-Rh(D) antibodies in isolation (95% confidence interval, 1.84-7.33). In the setting of multiple antibodies including anti-Rh(D), Rh-positive fetuses/neonates have an increased odds of developing significant hemolytic disease even if the fetus is negative for the other corresponding red blood cell antigen. CONCLUSION: Women with multiple red blood cell antibodies are more likely to develop significant hemolytic disease of the fetus and newborn than those with a single antibody especially in the presence of anti-(Rh)D. This pathophysiology may suggest a more aggressive immune response in women who develop more than 1 red blood cell antibody.

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OBJECTIVE: The aim of this study was to develop a simple clinical algorithm for prediction of donor and recipient death using 'yes'or 'no' questions through the process of recursive partitioning for patients undergoing laser therapy for twin to twin transfusion syndrome (TTTS). The intent was to identify a subset of patients with very high specificity to whom clinical decisions would be simplified. METHOD: Secondary analysis of data retrospectively collected from laser procedures was performed for TTTS at NAFTNet centers from 2002 to 2009. Preoperative factors associated with donor and recipient death were identified by recursive partitioning regression analysis. Classification And Regression Trees (CARTs) were developed to refine specificity for prediction of death. RESULTS: There were 466 TTTS patients from eight centers. CARTs were obtained for prediction of donor death. Improved specificity was achieved through recursive partitioning as demonstrated in receiver operator characteristic curves for prediction of death of the donor. There was less than optimal predictive ability for prediction of death in the recipient, as demonstrated by lack of generation of CARTs. CONCLUSION: Recursive partitioning improves the specificity and refines the prediction of donor fetal and neonatal demise in TTTS treated with laser therapy. This has the potential to improve therapeutic choices and refine counseling regarding outcomes.

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BACKGROUND: Intravenous immunoglobulin (IVIG) is a therapeutic agent used to prevent fetal thrombocytopenia in those pregnancies identified to be at risk for fetal and neonatal alloimmune thrombocytopenia. Although generally considered a safe medication, hemolytic anemia is a known side effect of IVIG treatment that may result in maternal medical complications. CASES: We present three cases of IVIG-induced maternal anemia from separate institutions that occurred during treatment for fetal and neonatal alloimmune thrombocytopenia and resolved after discontinuation or alteration of therapy. None of the treated fetuses had thrombocytopenia at birth. CONCLUSION: There is a potential for hemolysis when prescribing IVIG. We recommend laboratory monitoring for hemolytic anemia and suggest options for management including drug modification or cessation of therapy.

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OBJECTIVE: We seek to determine whether (1) mean abdominal circumference (AC) of fetuses with gastroschisis is smaller than published normative values, (2) diagnosis of AC ≤ 2.5th percentile is supported by postnatal diagnosis of small-for-gestational age (SGA) and (3) adverse neonatal outcomes are more common in fetuses affected by gastroschisis with a sonographically measured small AC. METHODS: Retrospective review of pregnancies complicated with gastroschisis between 2000 and 2008. Patient demographics, method of closure, length of stay, use of ventilator support and gastrointestinal complications were compared. RESULTS: Seventy-four fetuses were identified with 368 ultrasound observations. Mean AC of fetuses with gastroschisis fell between the 2.5th and 50th percentile for gestational age. Thirty patients had AC measurements ≤ 2.5th of which 50% were SGA at delivery. Eleven of the 74 fetuses were diagnosed with intrauterine growth restriction (IUGR) and all were SGA. Birth weight was lower in those with a small AC (2104 g vs. 2665 g, p<0.001). There were no other differences in outcomes. CONCLUSION: AC values fell within the normal range of normative curves. Fifty percent of fetuses with small AC were SGA at birth. Neonatal outcomes in patients with small AC are similar to those with a normal AC.

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Beckwith-Wiedemann syndrome is a rare congenital overgrowth syndrome. It carries important connotations for the pediatric urologist because it is associated with an increased risk for developing certain embryonal tumors. Until recently, these patients were not diagnosed until after birth; however, with newer imaging modalities, this syndrome may be diagnosed prenatally. We present a case of Beckwith-Wiedemann syndrome, depicting the prenatal modalities that may be used to diagnose this unusual condition.

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OBJECTIVE: To determine preoperative predictive factors for donor and recipient death after laser ablation of placental vessels in twin-to-twin transfusion syndrome. STUDY DESIGN: Retrospective analysis of North American Fetal Therapy Network center laser procedures, 2002-2009. Factors associated with donor and recipient death were identified by regression analysis. RESULTS: There were 466 patients from 8 centers. Factors significantly associated with donor fetal death were low donor estimated fetal weight (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.55-0.87) and reversed end diastolic velocity in the umbilical artery (OR, 4.0; 95% CI, 1.54-10.2); for recipient fetal death-low recipient estimated fetal weight (OR, 0.65; 95% CI, 0.44-0.95), recipient reversed "a" wave in the ductus venosus (OR, 2.39; 95% CI, 1.27-4.51) and hydrops (OR, 3.7; 95% CI, 1.1-12.7); for recipient neonatal death-low donor estimated fetal weight (OR, 0.54; 95% CI, 0.30-0.95), high recipient estimated fetal weight (OR, 1.55; 95% CI, 1.06-2.26) and recipient reversed end diastolic velocity in the umbilical artery (OR, 7.8; 95% CI, 1.03-59.3). CONCLUSION: Preoperative findings predict fetal and neonatal demise in twin-to-twin transfusion syndrome treated with laser therapy.

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OBJECTIVE: To determine whether prenatal management using guidelines established for anti-D is applicable to anti-Jka. STUDY DESIGN: A computerized database containing the records of all alloimmunized pregnancies at The Ohio State University Medical Center with due dates from 1959 to 2008 was used to identify pregnancies affected only by anti-Jka. Only cases with evidence that the newborn was Jka antigen positive were included. RESULTS: Twenty affected pregnancies met inclusion criteria. Of those, 16 pregnancies required monitoring with serum titers only and 4 were followed with more diagnostic tests as recommended during that time period. One pregnancy with the highest titer of 32 and elevated middle cerebral artery peak systolic velocity (MCA PSV) required 4 intrauterine transfusions for fetal anemia. Another pregnancy with a titer of 32 had an infant who required phototherapy for hemolytic disease of the fetus/newborn (HDFN), with a hemoglobin value of 15.9 g/dL. None of the other 18 infants required any therapy for HDFN. CONCLUSION: Our case series identified severe disease in 1 of 20 pregnancies from anti-Jka using maternal antibody titer and MCA PSV. Criteria used for monitoring RhD alloimmunization were effective in detecting severe HDFN resulting from to anti-Jka.

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BACKGROUND: The objective was to evaluate the management and outcome of patients with anti-Fy(a) at the Ohio State University. STUDY DESIGN AND METHODS: A database search for patients with pregnancies complicated only by anti-Fy(a) from 1959 to 2004. Collected information included maternal testing, fetal therapy, and neonatal outcomes. RESULTS: The final data set included 18 pregnancies in 15 women where anti-Fy(a) was the only maternal alloantibody present and the fetus was Fy(a) antigen-positive. Maternal antibody titers of at least 32 and optical density at 450 nm values in modified Liley Zone IIB or III identified all fetuses or neonates with significant hemolytic disease (2/18, 11%). No fetuses had hydrops, and there were no deaths attributed to hemolytic disease of the fetus and newborn. CONCLUSION: Anti-Fy(a) has the potential to lead to significant fetal hemolysis. Management guidelines developed for D sensitization are appropriate for pregnancies complicated by anti-Fy(a) alloimmunization.

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