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Experiments on ASDEX Upgrade (AUG) in 2021 and 2022 have addressed a number of critical issues for ITER and EU DEMO. A major objective of the AUG programme is to shed light on the underlying physics of confinement, stability, and plasma exhaust in order to allow reliable extrapolation of results obtained on present day machines to these reactor-grade devices. Concerning pedestal physics, the mitigation of edge localised modes (ELMs) using resonant magnetic perturbations (RMPs) was found to be consistent with a reduction of the linear peeling-ballooning stability threshold due to the helical deformation of the plasma. Conversely, ELM suppression by RMPs is ascribed to an increased pedestal transport that keeps the plasma away from this boundary. Candidates for this increased transport are locally enhanced turbulence and a locked magnetic island in the pedestal. The enhanced D-alpha (EDA) and quasi-continuous exhaust (QCE) regimes have been established as promising ELM-free scenarios. Here, the pressure gradient at the foot of the H-mode pedestal is reduced by a quasi-coherent mode, consistent with violation of the high-n ballooning mode stability limit there. This is suggestive that the EDA and QCE regimes have a common underlying physics origin. In the area of transport physics, full radius models for both L- and H-modes have been developed. These models predict energy confinement in AUG better than the commonly used global scaling laws, representing a large step towards the goal of predictive capability. A new momentum transport analysis framework has been developed that provides access to the intrinsic torque in the plasma core. In the field of exhaust, the X-Point Radiator (XPR), a cold and dense plasma region on closed flux surfaces close to the X-point, was described by an analytical model that provides an understanding of its formation as well as its stability, i.e., the conditions under which it transitions into a deleterious MARFE with the potential to result in a disruptive termination. With the XPR close to the divertor target, a new detached divertor concept, the compact radiative divertor, was developed. Here, the exhaust power is radiated before reaching the target, allowing close proximity of the X-point to the target. No limitations by the shallow field line angle due to the large flux expansion were observed, and sufficient compression of neutral density was demonstrated. With respect to the pumping of non-recycling impurities, the divertor enrichment was found to mainly depend on the ionisation energy of the impurity under consideration. In the area of MHD physics, analysis of the hot plasma core motion in sawtooth crashes showed good agreement with nonlinear 2-fluid simulations. This indicates that the fast reconnection observed in these events is adequately described including the pressure gradient and the electron inertia in the parallel Ohm’s law. Concerning disruption physics, a shattered pellet injection system was installed in collaboration with the ITER International Organisation. Thanks to the ability to vary the shard size distribution independently of the injection velocity, as well as its impurity admixture, it was possible to tailor the current quench rate, which is an important requirement for future large devices such as ITER. Progress was also made modelling the force reduction of VDEs induced by massive gas injection on AUG. The H-mode density limit was characterised in terms of safe operational space with a newly developed active feedback control method that allowed the stability boundary to be probed several times within a single discharge without inducing a disruptive termination. Regarding integrated operation scenarios, the role of density peaking in the confinement of the ITER baseline scenario (high plasma current) was clarified. The usual energy confinement scaling ITER98( p,y ) does not capture this effect, but the more recent H20 scaling does, highlighting again the importance of developing adequate physics based models. Advanced tokamak scenarios, aiming at large non-inductive current fraction due to non-standard profiles of the safety factor in combination with high normalised plasma pressure were studied with a focus on their access conditions. A method to guide the approach of the targeted safety factor profiles was developed, and the conditions for achieving good confinement were clarified. Based on this, two types of advanced scenarios (‘hybrid’ and ‘elevated’ q -profile) were established on AUG and characterised concerning their plasma performance.

The improved energy confinement mode (I-mode) is a potential candidate for future fusion power plants, as it combines ELM-free operation with good confinement. The unusual edge transport and turbulence in this regime is still not fully understood. This study analyzes the turbulent structure of the weakly coherent mode (WCM) in ASDEX Upgrade. Measurements from Doppler back-scattering and a thermal helium beam diagnostic are used to determine velocities of the background plasma and the WCM over multiple discharges. A phase velocity of the WCM of the order of 2–5 km s ^−1 in the electron diamagnetic drift direction is found, quantitatively close to a drift wave assuming negligible temperature fluctuations. A good agreement with a previously proposed mechanism behind the I-mode regime is observed. This marks the first experimental verification of a specific understanding of the WCM and the I-mode regime.

Introduction: Deaf and hard of hearing (DHH) women are faced with numerous health inequities, including adverse pregnancy and birth outcomes. These outcomes are likely exacerbated for Black DHH women because of the intersection of disability and race. This study aimed to explore the pregnancy and birth experiences of Black DHH women to identify factors that influence their pregnancy outcomes., Methods: Semistructured interviews were conducted between 2018 and 2019 with 67 DHH women who gave birth in the past five years. The present study represents a subgroup analysis of eight of the 67 women who self-identified as Black. Interviews were recorded, transcribed, and analyzed for emerging themes., Results: Primary themes centered on unmet needs, barriers, and facilitators. Barriers included limited access to health information owing to communication difficulties and challenges obtaining accommodations. Key facilitators included the availability of sign language interpreters, familial support, and cultural understanding from providers. Participants emphasized these facilitators in their recommendations to providers and DHH women. Findings also underscored the critical role of recognizing cultural identity in perinatal health care delivery., Conclusions: This study outlines themes that affect pregnancy and birthing experiences among Black DHH women in the United States. Study implications include a call to action for providers to prioritize communication accommodations, accessible information, and compassionate care for all Black DHH women. Furthermore, future work should explore the impact of cultural and racial concordance between patients and their health care providers and staff. Understanding how intersectional identities affect perinatal health care access is crucial for reducing disparities among Black DHH women., (Copyright © 2023 Jacobs Institute of Women's Health, George Washington University. Published by Elsevier Inc. All rights reserved.)

Objective: Women who are deaf experience higher rates of reproductive healthcare barriers and adverse birth outcomes compared with their peers who can hear. This study explores the pregnancy experiences of women who are deaf to better understand their barriers to and facilitators of optimal pregnancy-related health care., Design: Qualitative study using thematic analysis., Setting: Semi-structured, individual, remote or in-person interviews conducted in the USA., Sample: Forty-five women who are deaf and communicate using American Sign Language (ASL) and gave birth in the USA within the past 5 years participated in the interviews., Methods: Semi-structured interviews explored how mothers who are deaf experienced pregnancy and birth, including access to perinatal information and resources, relationships with healthcare providers, communication access and their involvement with the healthcare system throughout pregnancy. A thematic analysis was conducted., Main Outcome Measures: Barriers and facilitators related to a positive experience of perinatal care access among women who are deaf., Results: Three major themes emerged: (1) communication accessibility; (2) communication satisfaction; and (3) healthcare provider and team support. Common barriers included choosing healthcare providers, inconsistent communication access and difficulty accessing health information. However, when women who are deaf were able to use ASL interpreters, they had more positive pregnancy and birth experiences. Self-advocacy served as a common facilitator for more positive pregnancy and healthcare experiences., Conclusions: Healthcare providers need to be more aware of the communication and support needs of their patients who are deaf, especially how to communicate effectively. Increased cultural awareness and consistent provision of on-site interpreters can improve pregnancy and birth experiences for women who are deaf., (© 2022 John Wiley & Sons Ltd.)

To obtain accurate predictions of classifiers, model ensembles comprising multiple trained machine learning models are nowadays used. In particular, dynamic model ensembles pick the most accurate model for each query object, by applying the model that performed best on similar data. Dynamic model ensembles may however suffer, similarly to single machine learning models, from bias, which can eventually lead to unfair treatment of certain groups of a general population. To mitigate unfair classification, recent work has thus proposed fair model ensembles , that instead of focusing (solely) on accuracy also optimize global fairness . While such global fairness globally minimizes bias, imbalances may persist in different regions of the data, e.g., caused by some local bias maxima leading to local unfairness . Therefore, we extend our previous work by including a framework that bridges the gap between dynamic model ensembles and fair model ensembles. More precisely, we investigate the problem of devising locally fair and accurate dynamic model ensembles, which ultimately optimize for equal opportunity of similar subjects. We propose a general framework to perform this task and present several algorithms implementing the framework components. In this paper we also present a runtime-efficient framework adaptation that keeps the quality of the results on a similar level. Furthermore, new fairness metrics are presented as well as detailed informations about necessary data preparations. Our evaluation of the framework implementations and metrics shows that our approach outperforms the state-of-the art for different types and degrees of bias present in training data in terms of both local and global fairness, while reaching comparable accuracy., (© The Author(s) 2022.)

Cell therapies have significant therapeutic potential in diverse fields including regenerative medicine, transplantation tolerance, and autoimmunity. Within these fields, regulatory T cells (Treg) have been deployed to ameliorate aberrant immune responses with great success. However, translation of the cryopreservation strategies employed for other cell therapy products, such as effector T cell therapies, to Treg therapies has been challenging. The lack of an optimized cryopreservation strategy for Treg products presents a substantial obstacle to their broader application, particularly as administration of fresh cells limits the window available for sterility and functional assessment. In this study, we aimed to develop an optimized cryopreservation strategy for our CD4+CD25+Foxp3+ Treg clinical product. We investigate the effect of synthetic or organic cryoprotectants including different concentrations of DMSO on Treg recovery, viability, phenotype, cytokine production, suppressive capacity, and in vivo survival following GMP-compliant manufacture. We additionally assess the effect of adding the extracellular cryoprotectant polyethylene glycol (PEG), or priming cellular expression of heat shock proteins as strategies to improve viability. We find that cryopreservation in serum-free freezing medium supplemented with 10% human serum albumin and 5% DMSO facilitates improved Treg recovery and functionality and supports a reduced DMSO concentration in Treg cryopreservation protocols. This strategy may be easily incorporated into clinical manufacture protocols for future studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kaiser, Otto, McCallion, Hoffmann, Zarrinrad, Stein, Beier, Matz, Herschel, Hester, Moll, Issa, Reinke and Roemhild.)

Objective: To perform risk factor analysis for the prediction of hyperbilirubinemia in an African American male neonatal cohort., Study Design: A database of 500 previously published term and near-term African American male neonates was further analyzed to determine the role of risk factors for hyperbilirubinemia. Factors studied included birth weight >/=4.0 kg, gestational age /=75(th) percentile. Hyperbilirubinemia was defined as any bilirubin value >/=95(th) percentile on the hour-of-life-specific bilirubin nomogram., Results: Forty-three (8.6%) neonates developed hyperbilirubinemia. At 48 +/- 12 hours, median transcutaneous bilirubin was 8.3 mg/dL, 75(th) percentile 10.0 mg/dL, and 95(th) percentile 12.6 mg/dL. Of the risk factors, only exclusive breast-feeding, G-6-PD deficiency and predischarge bilirubin >/=75(th) percentile were significant (Adjusted Odds Ratios [95% Confidence Intervals; CI] 3.15 [1.39-7.14], P = .006; 4.96 [2.28-10.80], P = .001; and 7.47 [3.50-15.94], P < .0001, respectively). G-6-PD-deficient neonates who were also premature and breast-feeding had the highest incidence of hyperbilirubinemia (60%)., Conclusions: African American male neonates may be at higher risk for hyperbilirubinemia than previously thought. Screening for G-6-PD deficiency and predischarge bilirubin determination may be useful adjuncts in hyperbilirubinemia prediction in these newborns.

Background: The role of hemolysis in the mechanism and prediction of hyperbilirubinemia was contrasted between glucose-6-phosphate dehydrogenase (G-6-PD)-deficient and -normal African American neonates., Methods: Corrected end tidal carbon monoxide (ETCOc) values from the subset of male neonates born to non-smoking African American mothers, drawn from a previously published study, were analyzed. The relationship between ETCOc and bilirubin values, the latter represented as percentiles on the hour of life specific bilirubin nomogram, was determined. Hyperbilirubinemia was defined as any bilirubin value > or =95th percentile for hour of life., Results: 18.6% of 59 G-6-PD-deficient neonates developed hyperbilirubinemia, compared with 7.5% of 362 controls (relative risk 2.50, 95% confidence interval 1.31 to 4.76). As reported, ETCOc values (median, interquartile range) were significantly higher among G-6-PD-deficient neonates than controls (2.4 [2.0-2.9] vs. 2.1 [1.7-2.5] ppm, p<0.001. However, higher ETCOc values were limited to those G-6-PD-deficient neonates with lower bilirubin percentiles: among those whose bilirubin value did not exceed the 95th percentile ETCOc was 2.30 [2.00-2.85] vs. 2.00 [1.70-2.40] ppm in controls, p=0.001. In contrast, among the hyperbilirubinemic neonates ETCOc values were similar between G-6-PD-deficient neonates and controls: 2.7 [2.03-3.33] vs. 2.6 [2.33-3.45] ppm, p=0.9. In the G-6-PD-deficient neonates ETCOc > or =75th percentile contributed no additional predictive value for hyperbilirubinemia (likelihood ratio 1.8)., Conclusions: G-6-PD-deficient African American neonates have increased hemolysis and increased rate of hyperbilirubinemia, but the hemolysis is neither a predominant factor in the pathogenesis of hyperbilirubinemia nor is it predictive of hyperbilirubinemia, over and above the already increased risk conferred by G-6-PD deficiency.

Background: We determined values for glucose-6-phosphate dehydrogenase (G-6-PD) activity in African American neonates., Methods: G-6-PD activity was measured on umbilical cord blood from term and near-term healthy, male neonates. Neonates were stratified according to the number of neonates for each numerical unit of G-6-PD activity. Corrected end tidal carbon monoxide (ETCOc), a non-invasive index of hemolysis, was performed on each neonate. At least one predischarge transcutaneous bilirubin determination was performed., Results: Five hundred neonates were studied. Two subpopulations were apparent, with no overlap between the subgroups. Mean value for the 64 (12.8%) infants with the lower values (G-6-PD deficient) was 2.7+/-1.1 U/g Hb, range 0.4-6.6 U/g Hb, while that for the 436 neonates with the higher values (G-6-PD normal) was 21.8+/-2.9 U/g Hb, range 14.5-33.8 U/g Hb. No significant differences in activity were noted between those neonates <37 weeks gestational age and those >37 weeks. Enzyme activity in the lower range in both groups was not related to the development of hyperbilirubinemia. G-6-PD enzyme activity did not correlate with ETCOc values either for the entire cohort or for the individual subsets., Conclusions: G-6-PD-deficient neonates formed a separate subgroup from those with normal enzyme activity. The data supplied should facilitate interpretation of G-6-PD test results.

Background: Although glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is prevalent in African Americans, their risk of associated neonatal hyperbilirubinemia has not been prospectively studied., Objective: To compare hemolysis and the risk of hyperbilirubinemia among African American, G-6-PD-deficient neonates (study group) and G-6-PD-normal control subjects., Methods: Consecutive, healthy, term and near-term, male neonates born to African American mothers comprised the patient cohort. G-6-PD testing was performed with umbilical cord blood samples. Routine management included measurement of the end tidal carbon monoxide level corrected for ambient carbon monoxide level (ETCOc) within 4 hours after delivery (assessment of hemolysis), > or =1 predischarge bilirubin determination, and additional bilirubin testing as clinically indicated. Indications for phototherapy were identical for study patients and control subjects. Neonates were monitored for the first 1 week of life. ETCOc results, the incidence of hyperbilirubinemia (defined as a transcutaneous or plasma total bilirubin concentration of > or =95th percentile for the hour of life), and the need for phototherapy were compared between the G-6-PD-deficient and G-6-PD-normal groups., Results: Five hundred male patients were enrolled, of whom 64 (12.8%) were G-6-PD-deficient. ETCOc values (median and interquartile range) were higher among G-6-PD-deficient neonates than among control neonates (2.4 ppm [2.0-2.9 ppm] vs 2.1 ppm [1.7-2.5 ppm]). More G-6-PD-deficient neonates developed hyperbilirubinemia than did control subjects (14 of 64, 21.9%, vs 29 of 436, 6.7%; relative risk: 3.27; 95% confidence interval: 1.83-5.86), whereas 13 (20.3%) met the criteria for phototherapy, compared with 25 control subjects (5.7%) (relative risk: 3.53; 95% confidence interval: 1.91-6.56). No cases of kernicterus were observed., Conclusions: Within the African American neonatal population, there is a subgroup of G-6-PD-deficient infants with elevated rates of hemolysis, a higher incidence of hyperbilirubinemia, and a greater requirement for phototherapy, compared with G-6-PD-normal control subjects. These newborns should be monitored vigilantly for the development of hyperbilirubinemia.

Background: After initially successful smoking cessation the majority of patients relapse which stresses the addiction character of nicotine dependence. The patient and the physician, in therapeutic nihilism will not make another attempt for smoking cessation. In two randomised, double-blind, placebo-controlled trials in the US and Canada relapsed smokers, who had initially successfully quit smoking under Bupropion SR (Zyban), were again treated with Bupropion SR for smoking cessation. The encouraging results prompted us to perform a study in Germany under the conditions and temporal restraints of a routine medical practice., Methods/patients: In this open multicentre study 321 patients of a total of 365 patients at 62 study sites were included. The patients represented a healthy population (= free of severe chronic disease) of smokers, who had relapsed after a smoking cessation attempt with Bupropion SR or nicotine replacement therapy and were currently smoking at least 20 cig./d for > 3 months. The treatment with Bupropion SR (300 mg/d) lasted 7 weeks, with initial run-in of 150 mg/d for the first three days; motivational counselling was provided during 4 clinical visits within the study duration of 26 weeks., Results: 55.4 % of the patients were heavily or very heavily nicotine dependent as detected by the Fagerström Tolerance Questionnaire (score 6 - 11). The continuous abstinence rates for week 4 - 7 were 29.6 % (ITT) the point prevalence rates for week 26 were 30.5 % (ITT). Patients who showed a relapse had less daily cigarette consumption even after 26 weeks (10.3 cig./d versus 26.9 cig./d pretreatment). Nicotine craving reached a low plateau not earlier than week 6. Bupropion SR was well tolerated, only 9.7 % of the patients (ITT) withdrew from the study due to an adverse event. The most frequent adverse events were pain of the musculoskeletal system and insomnia., Conclusions: Bupropion SR was effective and well tolerated when given as an aid in smoking cessation in relapsed smokers.

Despite recent case reports of bilirubin encephalopathy in African American glucose-6-phosphate dehydrogenase (G6PD)-deficient neonates, there is a misconception that, in African Americans, G6PD deficiency need not be considered in the differential diagnosis of hyperbilirubinemia. We present a case of a hyperbilirubinemic African American female neonate in whom coexisting G6PD deficiency in the heterozygous state, and Gilbert's syndrome, were confirmed by DNA analysis. Hemolysis, predictive of the subsequent icterus, was documented by end-tidal carbon monoxide determinations at two time periods within the first 25 hours of life. A diagnosis of G6PD deficiency should be considered in African American neonates, females as well as males, with unexplained hemolysis or hyperbilirubinemia.

Objective: It is stated that the direct antiglobulin (Coombs') test (DAT) may be negative in ABO hemolytic disease of the newborn. Thus, significant jaundice in neonates who are A-B incompatible with their mothers but DAT test negative is often attributed to isoimmunization and another diagnosis is not sought. We wished to determine the rate of bilirubin production, as an objective measure of hemolysis, in 2 groups of DAT-negative neonates--ABO-compatible and ABO-incompatible--and in DAT-positive ABO-incompatible neonates., Methods: In consecutive, term, healthy newborns who were admitted to the general care nursery, we measured the level in parts per million (ppm) of end-tidal breath carbon monoxide (CO), corrected for inspired CO (ETCOc), an index of the rate of bilirubin production. We compared the levels in DAT-negative ABO-incompatible neonates with those in ABO-compatible neonates and with the levels in DAT-positive ABO-incompatible neonates. Statistical analysis was performed using 2-sample t and chi(2) tests., Results: There was no significant difference between the mean 12-hour ETCOc levels in DAT-negative ABO-incompatible neonates (n = 60, 2.2 +/- 0.6 ppm) versus DAT-negative ABO-compatible neonates (n = 171, 2.1 +/- 0.6 ppm), although there was a difference between the mean levels in DAT-positive ABO-incompatible neonates (n = 14, 3.4 +/- 1.8 ppm) and the DAT-negative groups. Four DAT-negative ABO-incompatible neonates had elevated ETCOc levels; in 2, we diagnosed a specific hematologic abnormality, namely, glucose-6-phosphate dehydrogenase deficiency in 1 and elliptocytosis in the other., Conclusion: In DAT-negative newborns with significant jaundice or increased bilirubin production, even if ABO-incompatible, a cause other than isoimmunization should be sought.

Objective: First, to determine the sensitivity, specificity, and positive predictive value (PPV) of the direct antiglobulin test (DAT) for significant hemolysis in the neonate, as referenced to end-tidal carbon monoxide, the criterion standard for estimating the rate of hemolysis; and second, to evaluate the predictive value of the two procedures for significant jaundice., Design: Consecutive term newborns admitted to the nursery of an inner-city university hospital over a 15-week period. DAT screening by the Blood Bank was performed on all. End-tidal carbon monoxide levels were obtained at 12+/-6 and at 24+/-6 hours of age. Infants of nonsmoking mothers whose 12-hour exhaled carbon monoxide level was > or = 95th percentile were defined as having significant hemolysis., Results: n=660; DAT was positive in 23 (3.5%). Using the 12-hour end-tidal carbon monoxide > or = 3.2 microl/l (> or = 95th percentile) as reference (n=499 nonsmokers), the sensitivity of the DAT was 38.5% (10 of 26) and specificity 98.5% (466 of 473) for the detection of significant hemolysis. The PPV of the DAT for significant hemolysis at 12 hours was 58.8% (10 of 17). For significant jaundice the PPV of end-tidal carbon monoxide was greater than that for DAT (65.4% vs 52.9%), although not statistically so (p=0.25). The negative predictive values were similar., Conclusion: DAT fails to identify over half of the cases of significant hemolysis that are diagnosed by end-tidal carbon monoxide. A neonate with a positive DAT has about a 59% chance of having significant hemolysis. End-tidal carbon monoxide may also provide a more sensitive index for predicting significant jaundice.

Glucose-6-phosphate dehydrogenase (G6PD) levels are not usually drawn in the evaluation of black neonates with hyperbilirubinemia because of the oft-stated opinion that the levels may be normal at the time of hemolysis and thus will be misleading. In fact, this opinion is not applicable to newborns as many studies have shown that deficiency in the conjugating ability of the liver, not hemolysis, is the main cause of neonatal jaundice associated with G6PD deficiency. We present a case report of a neonate with brisk hemolysis and hyperbilirubinemia in whom the G6PD level was abnormally low at the time of the hemolytic episode. DNA analysis showed him to have the A-(202A,376G) variant and, as well, the UGT1A1 promoter repeat polymorphism associated with Gilbert's disease. This case, as well as a review of the literature, indicates that enzyme levels are not normal in patients with G6PD A- who are undergoing hemolysis., ((c)2001 Elsevier Science.)

A 31-year-old primigravida with twins had spontaneous rupture of the membranes at 32 weeks' gestation. On admission, because of contractions, the mother was started on tocolytic magnesium sulfate (MgSO4) along with betamethasone and prophylactic antibiotics. About a day later, she was found to have magnesium toxicity. Her serum total magnesium level was 9.0 mg/dl. Tocolysis was immediately discontinued. At cesarean delivery the following day, twin A, a female, died at 30 minutes of age despite a vigorous resuscitation. Although the preceding fetal heart rate patterns had been reassuring and the umbilical blood gases were normal, quite unexpectedly, the Apgar scores were 1/1/0. An autopsy revealed no anatomic abnormalities. Twin B, a female who survived, was also intubated at delivery. During her stay in the Neonatal Intensive Care Unit, she was found to have modestly elevated levels of serum cardiotroponin T. In our opinion, it is probable that the death of twin A can be directly attributed to magnesium sulfate toxicity. Neonatologists who attend deliveries should be aware that unexpected death may occur in babies who were exposed to high doses of tocolytic MgSO4.

Optimal management of breastfeeding does not eliminate neonatal jaundice and elevated serum bilirubin concentrations. Rather, it leads to a pattern of hyperbilirubinemia that is normal and, possibly, beneficial to infants. Excessive frequency of exaggerated jaundice in a hospital or community population of breastfed infants may be a warning that breastfeeding policies and support are not ideal for the establishment of good breastfeeding practices. The challenge to clinicians is to differentiate normal patterns of jaundice and hyperbilirubinemia from those that indicate an abnormality or place an infant at risk.

Objective: Because of questions about the basis for the use of naloxone in resuscitation of the newborn, we wished to evaluate the use of naloxone at our institution and an affiliated hospital., Methodology: Evaluation of the actual use of naloxone at a university hospital and a community hospital: we document naloxone use by daily survey for a month in one; in the other, we perform a retrospective record review of 1 year's use., Results: The university hospital had 240 births during February, 1998. Naloxone was given twice: once, 7 minutes before delivery to a woman at term who had received opiates about 2 hours previously; and once, intramuscularly, to a premature infant for apnea, before being intubated. The community hospital had 2044 births during fiscal 1998. Twenty-six neonates were identified as having received naloxone. Of the 26, 13 received naloxone without needing ventilatory support; all 13 with respiratory depression had a predisposing perinatal complication., Conclusion: The use of naloxone in practice may not conform to the American Academy of Pediatrics' guidelines for use in resuscitation of the newborn. The use of naloxone in resuscitation of the newborn should be reevaluated.

ABO hemolytic disease of the newborn (HDN) occurs almost exclusively in infants of blood group A or B who are born to group O mothers because IgG anti-A or -B occurs more commonly in group O than in group A or B individuals. We report a case in which clinically significant ABO-HDN occurred in a group B neonate from anti-B of a group A2 mother. The IgG anti-B titer was much higher (256) than that found in a group A1 mother/infant control group (

This study evaluated whether a new predictive rule is more accurate for estimating the length of pregnancy in African Americans than Nägele's rule, the accepted standard. After identifying women in early pregnancy, telephone interviews were conducted to obtain information about 16 previously established determinants of gestational length. Based on these data, a linear multivariate regression model was used to predict an estimated delivery date (EDD) for each mother. In addition, the EDD was determined using Nägele's rule. Later, the actual delivery date was compared with the EDD predicted by the new rule and with the EDD predicted by Nägele's rule. Each pregnancy was assigned to its better prediction group, either the new rule's group or the Nägele's rule group. Fifty-seven pregnancies were identified prospectively and monitored. The new rule predicted the actual delivery date more accurately in 66% (37/56) of pregnancies, Nägele's rule was a better predictor in 34% (19/56) of pregnancies, and both rules were equally accurate in predicting the delivery date for one pregnancy. The new rule was more precise than Nägele's rule (P = .022) when the binomial distribution was used. When using the linear regression model rule, a more accurate EDD can be determined for African-American women. Moreover, it is possible to predict the risk of preterm delivery (those occurring > 3 weeks earlier than the EDD).

Objective: To assess the effectiveness of oral sucrose via a nipple compared with no treatment and dorsal penile nerve block (DPNB) for alleviating pain in neonatal circumcision., Design: Randomized control trial. Data analysis performed by investigators blinded to the 3 treatment groups., Setting: University teaching hospital, General Care Nursery., Patients: One hundred nineteen full-term male, normal birth weight neonates, 12 hours old or older., Interventions: No treatment (our standard care), DPNB, or oral sucrose prior to circumcision., Main Outcome Measures: Differences between groups in heart rate and oxygen saturation changes from baseline during specified intervals of the circumcision procedure. Differences between groups in loss of data due to episodes of excessive motion., Results: Sucrose gave significant (P < .001) pain relief compared with the no treatment control throughout most of the circumcision and particularly in the early stages of the procedure. Overall, the average difference in the elevation of heart rates during the circumcision operative procedure among the 3 groups and the 95% confidence intervals (CIs) were as follows: control vs DPNB, 27.1 beats/min (17.6, 36.6) and control vs sucrose, 9.7 beats/min (0.1, 19.3). Furthermore, newborns who received either DPNB or sucrose had less loss of oxygen saturation data due to excessive motion during the procedure than the no-treatment controls. The total percentages of lost data due to excessive motion in the 3 groups were 31% for control, 10% for DPNB, and 8% for sucrose. Relative risk and 95% CIs were: DPNB vs control, 0.32 (0.23, 0.43); sucrose vs control, 0.26 (0.18, 0.36). Differences in oxygen saturation among the 3 groups during the circumcision operative procedure were statistically (P < .001), but perhaps not clinically, significant. However, the analysis did not include missing data due to excessive motion, which occurred predominantly in the no-treatment control group., Conclusion: Sucrose on a pacifier is an inexpensive and effective method for pain relief in neonatal circumcision when DPNB is not desirable.

Objective: To examine the impact of changes in birth weight distribution in individual groups and in birth weight-specific fetal death rates on the decline in the crude fetal death rate in the United States., Methods: Data on live births and fetal deaths in the U.S. for the period 1979-1990 were examined by birth weight group and race using Kitagawa's method for analysis of the crude fetal death rate., Results: In the period 1979-1990, all racial groups had a decrease in the crude fetal death rate, more so in whites and others (about 22%) than in blacks (10%). In the white population, 73.4% of the total reduction in the crude fetal death rate was attributable to the improvement in birth weight-specific fetal death rates, and the remaining portion of the reduction was due to a favorable change in birth weight distribution. In the black population, the reduction in the crude fetal death rate was entirely attributable to the improvement in the birth weight-specific fetal death rates. However, in other groups, a favorable change in the birth weight distribution was the major determinant. Although black births represented 16.5% of all births in the U.S., they accounted for 26-29% of the crude fetal death rate. Disparity in the crude fetal death rates for blacks and whites is explained almost entirely by differences in birth weight distribution., Conclusions: A further decrease in the crude fetal death rate in the U.S. requires a decrease in low birth weights, particularly in blacks.

Neonatal intensive care has led to a progressive improvement in the survival of very low birth weight (VLBW, < 1,500 g) infants. However, it has not been established whether there has been a simultaneous increase or decrease in the prevalence of handicapping conditions in this group of children. To explore this question, a meta-analysis was performed using outcome data of 32 developmental studies of VLBW infants born in industrialized countries between 1947 and 1987. The authors' results show that the proportion of VLBW infants who survived and had an intact outcome progressively increased between 1947 and 1987--from 147 per 1,000 live births in the period 1947-1965 to 498 per 1,000 in the period 1980-1987 (p < 0.01). The prevalence of major handicapping conditions for the subset of VLBW infants who weighed < 1,000 g at birth increased, resulting from the increasing survival rates. However, the prevalence of major handicapping conditions among all children with VLBW decreased from 147 per 1,000 live births in 1947-1965 to 45 per 1,000 in 1980-1987 (p = 0.02). The authors' meta-analysis suggests that improved survival of VLBW infants has not been accompanied by an increase, but more likely a decrease, in the prevalence of handicapping conditions in this birth weight group.

To describe the clinical causes of fetal death in black women, we performed a record review of the primary causes of fetal deaths (n = 315, > or = 500 g or > or = 24 weeks' gestation) occurring over an 11-year period in a population of 26,852 black women who delivered at the Chicago Lying-in Hospital, University of Chicago Hospitals, Chicago, IL. The over-all fetal death rate (FDR) per 1,000 total births was 11.7, consistent with U.S. vital statistics data for blacks. The FDR per 10,000 births attributed to hypertension was nine times greater in our population than in a historical comparison population of Canadian white women: 19.5 (95% CI = 13.7, 25.4) versus 2.2 (P < .0001), respectively, although the prevalence of hypertension was only 1.2 times greater in the population of black women. Furthermore, hypertension in pregnancy accounted for 15% of the excess fetal mortality in our population of urban black women as compared to the population of Canadian white women. Health care providers should be aware of the risk of fetal death in hypertensive, innercity, U.S. black women.

We undertook a randomized, placebo-controlled, double blind trial of cytomegalovirus (CMV) immunoglobulin (CMVIG) for prevention of CMV-associated disease in 183 multiply transfused, premature neonates. CMVIG (150 mg/kg) or placebo was given within 24 hours of the first transfusion and at Day 10. If an intravenous catheter was still in place an additional dose was given between Days 20 and 30. The globulin and placebo groups were well-matched with respect to birth weight, gestational age, Apgar score, birth to a CMV-seropositive mother, requirement for assisted ventilation and exposure to CMV-positive, unscreened blood products. Among infants followed for more than 10 days, 18 (10.5%) developed CMV infection; 9 had symptomatic CMV disease (5 placebo; 4 CMVIG). Among infants born to a CMV-seropositive mother, CMVIG use was associated with a CMV syndrome rate of 3.2% (95% confidence interval, 0.2 to 18.5%) compared to 12.5% (95% confidence interval, 4.5 to 27.6%) among placebo recipients (P = 0.163). Among placebo recipients infants born to CMV-seropositive mothers were more likely to have a virologically confirmed CMV syndrome than those born to a CMV-seronegative mother, despite receipt of blood not screened for CMV antibody (P = 0.012). Multivariate analysis demonstrated that two factors were independently associated with CMV acquisition: the volume of CMV-seropositive blood products transfused (P = 0.005); and birth to a CMV-seropositive mother (P = 0.006). Infusions of CMVIG were well-tolerated. This study reaffirms that perinatally acquired CMV disease is more common among infants born to CMV-seropositive mothers than CMV-seronegative mothers, even without use of CMV-screened blood products.

We sought to determine by what amount the frequency of low birth weight (LBW) could be reduced by eliminating its known, preventable risk factors. Based on the prevalence of risk factors such as cigarette smoking (exposure) in a population, and the degree of association (relative risk) between the risk factors and the outcome of LBW, we estimated the percentage of LBW in the United States attributable to the risk factors (population-attributable risk percentage). We found the following associations with known preventable LBW: Cigarette smoking accounts for 9.6%; alcohol consumption during pregnancy, 2.3%; low pre-pregnancy weight (less than 54 kg), 6.3%; urinary tract infections, 1.3%; Chlamydia trachomatis genital infections, 4.8%; and narcotics addiction, 3.8%. Because these risk factors are not mutually exclusive, eg, narcotics addicts may be addicted to both narcotics and cigarettes, the maximum preventable population-attributable risk percentage for LBW is less than the sum of the individual risk factors, which is 28.1% (9.6% [cigarette smoking] + 2.3% [alcohol consumption] + 6.3% [low pre-pregnancy weight] + 1.3% [urinary tract infection] + 4.8% [Chlamydia] + 3.8% [narcotics addiction] = 28.1%). Given the current state of knowledge about preventable risk factors, LBW can be reduced--in an idealized model--from only 6.9 to 5.0% of all births. In a more realistic model, we estimate that LBW can be reduced from only 6.9 to 6.3% of all births. Therefore, a national effort is indicated to identify unknown preventable causes of LBW.

We suggest an explanation for a pediatric paradox: the low-birthweight-specific (LBW) neonatal mortality rate (NMR) for black infants is less than the NMR for white infants, even though the overall NMR for black infants is about twice the overall NMR for white infants. Analyzing the Delivery Interview Program data set--a large matrix of information collected at the Boston Hospital for Women (now the Brigham and Women's Hospital)--we found that, overall, black infants' gestations are about four days shorter than white infants'. However, after stratifying by birthweight, we found a reversal in our data, namely, LBW (< 2,500 g) black infants' gestations are seven days longer than the gestations of LBW white infants. We believe that this increased chronological maturity may account for some of the survival advantage of the LBW black infant compared with the LBW white infant of the same weight.

Chlorpromazine and thioridazine are widely used antipsychotic agents that are extensively metabolized. Parent compounds and metabolites have diverse pharmacologic activities, and differences in patterns of metabolism may explain differences in therapeutic and side effects from individual to individual. Radioreceptor assays were used to determine the neuroleptic, antimuscarinic, and anti-alpha-noradrenergic potency of chlorpromazine, thioridazine, and their metabolites. The results indicate that these metabolites show a wide range of potencies. The spectrum of activity of a metabolite may be quite different from that of its parent compound. The clinical relevance of these findings to individual differences in drug response is discussed. The combined use of radioreceptor assays and chemical assays in future clinical research is proposed.

The effect of mode of delivery on the mortality and morbidity of 26- to 32-week neonates was studied. Five hundred six consecutive deliveries at 26 to 32 weeks' gestation were reviewed. The populations were divided into high-risk and low-risk neonates by evaluation of antepartum variables known to increase neonatal risk, ie, abruptio placenta. One hundred ninety-six infants were classified as low risk. In this group, 124 vaginal and 72 cesarean section deliveries were compared using demographic, peripartum, and neonatal variables. Cesarean delivery was associated with highly significant maternal morbidity, including a 30% incidence of vertical uterine incision. No difference in neonatal mortality was shown. Cesarean delivery was associated with lower one-minute Apgar scores and a greater incidence and severity of hyaline membrane disease. No neonatal differences were shown in the incidence of trauma, intraventricular hemorrhage, or seizures. This study does not support cesarean delivery of all tiny neonates.

Specific developmental dyslexia, a condition characterized by reduced reading, spelling, and writing abilities combined with normal intellectual capacity, has challenged geneticists and 'environmentalists.' Although most of the strikingly controversial results can be traced to differences concerning diagnostic decision-making, there are many hints of a genetic contribution. Twin studies and extensive pedigree analysis substantiate this view, but it is too early to infer a definite mode of inheritance from the available data.

Factors affecting the survival of 136 consecutive live-born infants delivered at 24 to 28 weeks' gestation during a 4-year period were analyzed. After careful assessment of gestational age, perinatal care for the fetus of at least 26 weeks' gestation was aggressive. Survival at 26 weeks was 45% and at 28 weeks, 92%. Multivariate analysis showed that the set of variables that best predicts neonatal outcome is gestational age, antepartum glucocorticoid administration, and resuscitation at birth.

Ina a sample of 48 healthy adult male twin pairs (24 MZ, 24 DZ) the activities of DBH (serum), COMT (red blood cells), and MAO (platelets) were determined. The twins had undergone a detailed psychodiagnostic test procedure before. Interindividual variability of enzyme activities is almost exclusively genetically determined. No correlation between enzyme activities within one subject is found. Correlations between enzyme activities and MMPI test scores were calculated. As in a comparable investigation by Murphy et al. (1977), negative correlations between MAO activity and MMPI scores prevailed.

Striking circadian changes in behavioral sensitivity to haloperidol were found by measurements of cataleptic responses in rats trained in a controlled lighting cycle (lights on, 7:00 a.m.--7:00 p.m.). Thus, catalepsy was maximal at about 4:00 p.m. and minimal at about 4:00 a.m., virtually the opposite of the circadian rhythm of spontaneous behavioral activity in drug-free rats. At a given dose of haloperidol, catalepsy scores differed 2- to 3-fold, and the ED50 shifted left nearly 10-fold from a.m. to p.m. After fixed doses of haloperidol, tissue levels of the drug, as determined by a sensitive and selective radioreceptor assay, differed by 2- to 6-fold through the 24 hr cycle and brain levels closely followed the circadian changes in behavior. These results suggest a pharmacokinetic contribution to the circadian changes in behavioral response, although additional pharmacodynamic factors are also considered.