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Background: Raising the median age at first sexual intercourse and first marriage among females is a policy goal of the Ethiopian government. Education figures prominently in the government's plans for achieving its goals, including primary and secondary schools; higher education; and out-of-school interventions such as youth centers, peer clubs, and youth associations In this study, we tested whether adolescents and youth who had high educational and occupational expectations at younger ages were at a lower risk of first sexual intercourse and marriage during adolescence and early adulthood., Methods: Data came from multiple waves of a longitudinal survey of households and adolescents conducted in southwestern Ethiopia. A measure of career expectations was created from educational and occupational expectations measured at baseline when the adolescents were ages 13-17. The occurrence and timing of first sexual intercourse (called first sex) and marriage were measured four years later in a wave 3 survey. Discrete-time logistic hazard regression models were applied to a person-year file to predict first sex for males and females separately and first marriage for females., Results: Male and female adolescents who had high career expectations at young ages were at a significantly lower risk of first sex during adolescence and early adulthood. Unlike the delaying effect of being in school, the effect of high career expectations did not wear off as adolescents aged. Among female adolescents, delaying first sex, staying in school, and having parents who desired them to marry at older ages were all associated with a significantly lower risk of marriage during adolescence and early adulthood., Conclusions: The educational and occupational expectations and family plans that youth develop early in adolescence influence the timing of the transition into sexual activity and marriage. Ethiopian youth who develop high career expectations delay first sex, which for female youth is a key predictor of age at first marriage. Adolescents' perceptions of parents' expectations for them are strongly associated with their own expectations and behavior., (© 2022. The Author(s).)

Purpose: Accurate measures of violence are difficult to obtain from self-reported data because of stigmatization and social undesirability of the topic. Most methods that attempt to reduce such biases require literacy and either remove the benefits of interviewer guidance or do not give individual-level results. We tested a low-tech nonverbal response card that avoids revealing interviewees' responses to interviewers while retaining interviewer support among adolescents in communities with very low educational attainment., Methods: As part of a broader health questionnaire, we asked a sample of 1,644 adolescents, aged 12-20 years, in northwestern Burkina Faso about their experiences of physical and sexual violence. We randomized participants to either a conventional verbal response arm or a nonverbal response card arm where respondents' answers were unspoken and not displayed to interviewers. We first evaluated response validity and reliability in each arm, then compared prevalence rates across arms and evaluated whether any differences varied by respondent characteristics using regression models., Results: The level of internal reliability of responses among nonverbal respondents was similar to or greater than that of verbal respondents. Nonverbal respondents reported similar patterns of physical assault and sexual debut as verbal respondents but significantly higher levels of sexual assault and forced sex. These differences were broadly similar across sample subgroups defined by age, gender, proneness to social desirability, and mental health., Conclusions: Nonverbal response cards offer a practical and beneficial method for reducing underreporting of stigmatized and traumatic experiences while maintaining data quality in low-literacy populations., (Copyright © 2020 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: This study examines the roles of parents, extended kin, and exchange networks in adolescent health-seeking behavior in Ethiopia., Background: Prior studies highlight the role of mothers in children's health, whereas fathers, extended kin and other network partners remain largely unexamined. The gender intensification hypothesis suggests that adolescents gravitate toward same gender parents for advice and assistance with health-related issues. A more expansive view of the hypothesis suggests that other same gender adults may also be important sources of support., Method: Survey data were used from a random sample of 2,084 youth ages 13-17 collected in urban and rural communities in southwestern Ethiopia. Sources of advice, treatment, and accompaniment to get treatment were examined. Random intercept logistic regression models were used to identify factors associated with receipt of formal health care., Results: Fathers and mothers played an important role in all phases of adolescent health-seeking behavior. Fathers' involvement was especially common in rural areas and more so with boys than girls. Extended kin and exchange networks also played a role and were even more important for boys in female-headed households, suggesting they may have substituted for absent fathers., Conclusion: Adolescents rely heavily on parents and other adults for health advice and treatment. Who children go to for assistance is highly gendered, especially in rural areas., Implications: Studies of adolescent health-seeking and interventions designed to improve health services utilization need to recognize the important involvement of parents and other closely related adults in advising youth and accompanying them to get treatment.

This analysis draws on binational data from an ethnosurvey conducted in Guatemala and in the United States in Providence, Rhode Island, to develop a refinement of the weighting scheme that the Mexican Migration Project uses. The alternative weighting procedure distinguishes between temporary and settled migrants by using a question on household location in the Guatemala questionnaire that is not used in the MMP. Demographic characteristics and integration experiences of the most recent U.S. trip are used to assess the composition and representativeness of the U.S. sample. Using a composite index of migrant integration to compare the impact of alternative U.S. sample weights on point estimates, I find that although the U.S. sample is broadly representative across a range of background characteristics, the MMP sample weighting procedure biases estimates of migrant integration downward.

Recent studies indicate that relatively few genomic regions are repeatedly involved in the evolution of Heliconius butterfly wing patterns. Although this work demonstrates a number of cases where homologous loci underlie both convergent and divergent wing pattern change among different Heliconius species, it is still unclear exactly how many loci underlie pattern variation across the genus. To address this question for Heliconius erato, we created fifteen independent crosses utilizing the four most distinct color pattern races and analyzed color pattern segregation across a total of 1271 F2 and backcross offspring. Additionally, we used the most variable brood, an F2 cross between H. himera and the east Ecuadorian H. erato notabilis, to perform a quantitative genetic analysis of color pattern variation and produce a detailed map of the loci likely involved in the H. erato color pattern radiation. Using AFLP and gene based markers, we show that fewer major genes than previously envisioned control the color pattern variation in H. erato. We describe for the first time the genetic architecture of H. erato wing color pattern by assessing quantitative variation in addition to traditional linkage mapping. In particular, our data suggest three genomic intervals modulate the bulk of the observed variation in color. Furthermore, we also identify several modifier loci of moderate effect size that contribute to the quantitative wing pattern variation. Our results are consistent with the two-step model for the evolution of mimetic wing patterns in Heliconius and support a growing body of empirical data demonstrating the importance of major effect loci in adaptive change.

Purpose: Deriving accurate estimates of the level of sexual coercion is challenging because of the stigma that is attached to the experience. This study examines the effectiveness of a nonverbal response-card method to reduce social desirability bias in reports of the conditions of sexual initiation among youth in southwestern Ethiopia., Methods: The conditions surrounding sexual initiation are examined using data from a pilot survey and a final survey of youth aged 13-24 years. Half of the respondents in each survey were randomly assigned to a nonverbal response-card method for sensitive questions on sexual attitudes and behavior, and the other half of the respondents were assigned to a control group that provided verbal responses. Responses for the two groups to questions regarding the conditions of sexual initiation are compared., Results: Respondents who used the nonverbal response card were more likely to report pressure from friends or a partner, having sex for money or another gain, and rape as conditions of sexual initiation than those who provided verbal responses. Among sexually experienced youth, 29.3% of respondents who used the card method reported some form of coercion during sexual initiation compared with 19.4% of respondents who gave verbal responses., Conclusions: The nonverbal response card provides an effective method for reducing social desirability bias when soliciting responses to sensitive questions in the context of an interviewer-administered survey. The analysis also suggests that coerced sexual initiation is underreported by youth in interviewer-administered surveys that use conventional verbal responses., (Copyright © 2012 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

The accurate assessment of risky sexual behaviors and barriers to condom use is essential to reduce the spread of HIV/AIDS. This study tests a new nonverbal response-card method for obtaining more accurate responses to sensitive questions in the context of face-to-face interviewer-administered questionnaires in a survey of 1,269 Ethiopian young people aged 13-24. Comparisons of responses between a control group that provided verbal responses and an experimental group that used the card indicate that the prevalence of nonmarital sexual intercourse may be two times higher and knowledge of condom access may be 22 percent lower in the study than typical population-survey methods suggest. These results suggest that our nonverbal response-card method yields less biased estimates of risky adolescent sexual behavior and perceived access to condoms than those derived from conventional face-to-face interviewer-administered surveys, and that this method provides an effective, easy-to-use, low-cost alternative.

We present a method for dividing the historical development of community migration streams into an initial period and a subsequent takeoff stage with the purpose of systemically differentiating pioneer migrants from follower migrants. The analysis is organized around five basic research questions. First, can we empirically identify a juncture in the historical development of community-based migration that marks the transition from an initial stage of low levels of migration and gradual growth into a takeoff stage in which the prevalence of migration grows at a more accelerated rate? Second, does this juncture point exist at roughly similar migration prevalence levels across communities? Third, are first-time migrants in the initial stage (pioneers) different from first-time migrants in the takeoff stage (followers)? Fourth, what is the nature of this migrant selectivity? Finally, does the nature and degree of pioneer selectivity vary across country migration streams?

Wing pattern evolution in Heliconius butterflies provides some of the most striking examples of adaptation by natural selection. The genes controlling pattern variation are classic examples of Mendelian loci of large effect, where allelic variation causes large and discrete phenotypic changes and is responsible for both convergent and highly divergent wing pattern evolution across the genus. We characterize nucleotide variation, genotype-by-phenotype associations, linkage disequilibrium (LD), and candidate gene expression patterns across two unlinked genomic intervals that control yellow and red wing pattern variation among mimetic forms of Heliconius erato. Despite very strong natural selection on color pattern, we see neither a strong reduction in genetic diversity nor evidence for extended LD across either patterning interval. This observation highlights the extent that recombination can erase the signature of selection in natural populations and is consistent with the hypothesis that either the adaptive radiation or the alleles controlling it are quite old. However, across both patterning intervals we identified SNPs clustered in several coding regions that were strongly associated with color pattern phenotype. Interestingly, coding regions with associated SNPs were widely separated, suggesting that color pattern alleles may be composed of multiple functional sites, conforming to previous descriptions of these loci as "supergenes." Examination of gene expression levels of genes flanking these regions in both H. erato and its co-mimic, H. melpomene, implicate a gene with high sequence similarity to a kinesin as playing a key role in modulating pattern and provides convincing evidence for parallel changes in gene regulation across co-mimetic lineages. The complex genetic architecture at these color pattern loci stands in marked contrast to the single casual mutations often identified in genetic studies of adaptation, but may be more indicative of the type of genetic changes responsible for much of the adaptive variation found in natural populations., Competing Interests: The authors have declared that no competing interests exist.

Context: Levels of modern contraceptive knowledge and use among people living in rural areas of Guatemala differ substantially from those of people living in urban areas. Understanding the pace and extent of rural-to-urban migrants' adoption of urban contraceptive practices is important in determining if there is a strong need for migrant-focused reproductive health programs., Methods: Bivariate and multivariate analyses of data on 971 married male and female respondents in the 1999 Guatemalan Migration and Reproductive Health Survey were used to examine how migration status and duration of residence in an urban area are associated with knowledge of modern contraceptive methods and current contraceptive use., Results: Migrants' contraceptive knowledge was positively associated with the number of years they had lived in an urban area. Mayan migrants in Guatemala City did not accumulate contraceptive knowledge at the same rate as non-Mayan migrants, perhaps due to cultural and linguistic barriers to obtaining knowledge of and access to contraceptives. Rural-to-urban migrants eventually achieve a level of modern contraceptive use slightly below that of urban nonmigrants, with the level of contraceptive knowledge being an important factor associated with use of modern methods., Conclusions: Migrants possess limited knowledge of modern contraceptive methods and, therefore, may experience unmet need for contraception or may have a limited choice of modern contraceptive methods during their first years in an urban destination. Programs designed to raise contraceptive awareness and use should target recent migrants--particularly indigenous Mayans--in urban areas.

This article examines the relationship between migration and the use of formal maternal health-care services among rural women in Guatemala. We identify assimilation, diffusion, and remittances as three potential pathways through which migration can affect health-care service utilization in rural areas. Using data from the 1995 Guatemalan Survey of Family Health and multi-level regression models, we estimate the impact of migration experience at the individual, household, and community level on the use of formal prenatal care and delivery assistance. We find that urban migration experience and having relatives abroad are associated with a greater likelihood of formal prenatal care utilization, after taking account of background characteristics and enabling resources. Migration experience at all levels is also strongly associated with formal delivery assistance; however, this association operates primarily through the positive association between migration and enabling resources. The differential effects of out-migration on maternal health-care service utilization reflect the different barriers to service use that exist for formal prenatal care and delivery assistance. Financial cost and geographic access are the most important barriers to formal delivery assistance, whereas awareness and acceptance remain as important barriers to the use of formal prenatal care in rural Guatemala. Urban migration experience and social ties to urban and international migrants lower the barriers to formal maternal health-care utilization through the acquisition and diffusion of new ideas and practices, and the return flow of financial resources.

Animal studies have shown that induction of cytochrome P450 (CYP) in the lung by oxygen exposure may result in the release of free radical oxidants and arachidonic acid metabolites, which can cause lung injury that is reduced by treatment with cimetidine, a CYP inhibitor. To determine whether cimetidine would reduce lung injury in human infants at risk for chronic lung disease, we conducted a randomized clinical trial in which we administered either cimetidine or a placebo for 10 d beginning < 24 h after birth to 84 newborn infants weighing < or = 1250 g who were receiving O2 and mechanical ventilation. Cimetidine had no significant effect on severity of respiratory insufficiency assessed at 10 d postnatal age. F2-isoprostane levels (a marker of oxidant injury) in tracheal aspirates were significantly higher in the cimetidine group at 4 d and at 10 d. There were no significant differences between the groups in tracheal aspirate levels of inflammatory markers (leukotriene B4, IL-8, and nucleated cell count) or arachidonic acid metabolites. We conclude that cimetidine does not reduce lung injury in newborn premature infants receiving O2 and mechanical ventilation. It is possible that cimetidine was not an adequate CYP inhibitor in this context.

This article uses the concept of social networks as it is employed in the research literature on family planning and migration to explore the impact of out-migration on modern contraceptive knowledge and use in rural Guatemala. Data for this study come from the 1995 Guatemalan Survey of Family Health. Results from multilevel regression models indicate that urban migration experience, having migrant kin in urban or international destinations, and living in a community where urban migration is common are all associated with greater contraceptive knowledge. Social ties to urban or international migrants are also associated with a greater likelihood of modern contraceptive use among married women, but this association works primarily through increased contraceptive knowledge. The findings of significant diffusion effects provide support for recent theories of fertility decline that emphasize the role of social interactions.

Between 1990 and 2000, the total fertility rate (TFR) in Ethiopia declined moderately from 6.4 to 5.9 children per woman of reproductive age. During the same period, the TFR in the capital city of Addis Ababa declined from 3.1 to 1.9 children per woman. Even more striking than the magnitude of this decline is that it occurred in the absence of a strong and effective national family planning program. In this study, the components of this fertility decline are identified using the Bongaarts framework of the proximate determinants of fertility. The results of a decomposition analysis indicate that a decrease in the age-specific proportions of women who are married, followed by an increase in contraceptive use are the most important mechanisms by which fertility has declined in Addis Ababa. Poor employment prospects and relatively high housing costs are likely factors that encourage couples to delay marriage and reduce marital fertility.

In a previous study of very low birth weight neonates, < or = 1500 g, admitted to the Vanderbilt University Neonatal Intensive Care Unit (NICU) from 1976-1990, improvements in survival were accompanied by a corresponding increase in the incidence of bronchopulmonary dysplasia (BPD). Since then, certain neonatal and perinatal interventions have been introduced and may influence neonatal outcomes. In this study, we have continued the analysis of the incidence of 3 outcomes: 1) Neonatal death (NEOD), 2) BPD, and 3) NEOD or BPD (NEOD/BPD) for an additional 7 years, 1991-1997. A retrospective study was performed of 3,837 patients with birth weight < or = 1500 g and admitted to the Vanderbilt NICU within 24 hours of birth from 1976 through 1997. The outcomes NEOD, BPD, or NEOD/BPD were modeled by using multiple logistic regression with the following risk factors included as covariates: birth weight, gestational age, Apgar scores at 1 and 5 minutes, gender, race, birth location, diagnosis of hyaline membrane disease, maternal age, maternal diabetes, delivery method, multiple births, duration of ruptured membranes, and biologically relevant interactions among these covariates. To assess time trends in the risk factors and outcomes, patients were divided into time periods (1 = 1976-80, 2 = 1981-85, 3 = 1986-90, 4 = 1991-95, and 5 = 1996-97). For each outcome, only covariates or interactions among covariates found to be significant were retained in the final model. Adjusted odds ratios and 95% confidence intervals were calculated to measure the risk associated with a given time period in comparison to the preceding period. There was a progressive decline in NEOD across all time periods. The previously described increase in BPD from period 1 through period 3 is followed by a decrease in periods 4 and 5. The risk of NEOD/BPD remained fairly constant from period 1 to period 3, but then showed a significant decrease over the two most recent periods. Prior to 1991, the cost of improved survival among very low birth weight infants in this large NICU was an increased incidence of BPD. Since 1991, the risk of BPD has been decreasing even though survival continues to improve. If these findings are also representative of other NICUs, they signify an important reduction in the impact of BPD as one of the costly sequelae of prematurity.

Role incompatibility, education as an investment in human capital, and schooling as a transformative experience are three mechanisms that link women's education to the timing of marriage and first birth. We simultaneously evaluate these different explanations using retrospective life history data for two cohorts of Mexican women collected in a nationally representative sample. Our analyses provide evidence in support of all three hypotheses. While in school young women are at a substantially lower risk of marriage and of a first birth. We find no evidence that women leave school to enter into unions nor do we find evidence that the effect of being a student diminishes with age. Women who work for a wage are also at a lower risk of marriage and a first birth. Once we control for student and employment status, the direct effects of cumulative education on family formation are relatively modest, although cumulative education is strongly associated with positive attitudes towards women's work and a significant increase in the likelihood of premarital and postmarital employment.

Research conducted in developing countries clearly demonstrates the positive effects of breastfeeding and widely spaced births on infant survival. The evidence is less clear as to whether these beneficial effects extend into early childhood, and under what conditions. In this paper we examine the effects of breastfeeding and birth spacing on neonatal, post-neonatal, and early childhood mortality in Ethiopia using data from the 1990 National Family and Fertility Survey. Our results provide clear evidence that the increased mortality risks associated with closely-spaced births continue beyond the first year of life into early childhood. Competition between siblings for food and maternal attention is the most probable explanation for this finding. We also find that breastfeeding beyond the second year of life is associated with higher mortality. Given that delayed weaning in Ethiopia is a common response to food shortages, we interpret this finding as further evidence of the negative consequences of resource deprivation for child survival.

We examine recent fertility trends in Ethiopia for evidence of short- and long-term responses to famine, political events, and economic decline. We use retrospective data on children ever born from the 1990 National Family and Fertility Survey to estimate trends in annual marital conception probabilities, controlling for women's demographic and socioeconomic characteristics. The results of our analysis provide evidence of significant short-term declines in conception probabilities during years of famine and major political and economic upheaval. In the longer term, marital fertility in both urban and rural areas declined in the 1980s after increasing moderately in the 1970s.

Previous studies suggest that urine-borne pheromones play an important role in lobster agonistic and sexual behaviour. This paper investigates the pattern of urine release in catheterised, but otherwise freely moving, adult lobsters with respect to feeding, social and non-social activities. Lobsters on average released 4.1 ml (1 % of body mass) of urine over a 12 h period; this more than doubled to 10.6 ml over the 12 h period after feeding. Hourly monitoring revealed that most urine was released in the first hour after feeding (2.84 ml). With the exception of the first hours after feeding, urine release was intermittent, with pauses lasting up to 17 h. The probability of urine release per hour in unfed lobsters was 0.34 (median); this value increased during agonistic interactions elicited by the introduction of a conspecific (median 0. 63) and during activity initiated by non-social disturbance (median 0.56). Mean urine volume during output hours in unfed lobsters amounted to 1.09 ml h-1. This volume was significantly increased by the presence of a conspecific (1.88 ml h-1) and decreased during activity initiated by non-social disturbances (0.56 ml h-1). No sex-specific differences in urine release were found. The data demonstrate that lobsters control their urine release in a manner dependent on behavioural context. This supports recent findings suggesting the use of urine for chemical signalling in agonistic interactions.

: This report describes a method for the determination of species identity of newly hatched larvae of five sympatric Hawaiian amphidromous gobioids (Lentipes concolor, Sicyopterus stimpsoni, Awaous guamensis, Stenogobius hawaiiensis, and Eleotris sandwichensis). Polymerase chain reaction (PCR) was used to amplify a homologous section of the cytochrome b (Cyt b) region of the mitochondrial genome (mtDNA) from adults of all five species. The resulting PCR-amplified DNA was subjected to restriction fragment length polymorphism (RFLP) analysis producing species-specific restriction patterns. PCR products from the five species were sequenced to substantiate correct amplification, restriction site locations, and fragment sizes. The sequence data were also used to construct a phylogenetic tree. Individual, newly hatched, wild-caught larvae of amphidromous gobioids of unknown species affinity were sorted into six morphotypes based on physical characteristics. These typed larvae and those from two species that spawned in captivity were subjected to the same molecular analysis as the adults. The RFLP results from adults and larvae were compared, allowing larval morphotypes to be assigned to the appropriate species. These comparisons permitted construction of an identification key to the newly hatched larvae of these species based solely on physical characteristics for use in future field studies.Key Words: fish larvae, species identification, Hawaii, gobioidea, PCR, RFLP.http://link.springer-ny.com/link/service/journals/10126/bibs/1n2p167.html

This paper uses retrospective life history data to assess the impact of family planning services on contraceptive use in a rural Mexican township. Between 1960 and 1990 contraceptive use rose and fertility declined dramatically. Both contraceptive supply and demand factors were influential in these trends. The start of the government-sponsored family planning programme in the late 1970s was associated with a sharp rise in female sterilization and use of the IUD. However, once we controlled for the changing socio-economic and demographic characteristics of the sample, the presence of family planning services had no significant effect on the likelihood that women used modern reversible methods compared to traditional methods. Men and women expressed concerns about the safety of modern methods such as the pill and the IUD. Efforts to increase modern contraceptive use should place greater emphasis on communicating the safety of these methods and improving the quality of services.

Surfactant deficiency in newborn infants with hyaline membrane disease (HMD) reduces peripheral airway stability, leading to lung atelectasis, inhomogeneity of distribution of ventilation, ventilation/perfusion mismatch, and hypoxemia. The aim of this study was to evaluate the immediate effect of exogenous surfactant treatment on ventilation inhomogeneity (VIH) in infants with HMD. Homogeneity of ventilation was measured repeatedly in ten infants (median gestational age 30 weeks and birthweight 1.50 kg) after Exosurf, and in six infants (median gestational age 30 weeks and birthweight 1.42 kg) after Survanta treatment. Lung function was measured before and 0.5, 2, and 6 hours after administration of a single dose of surfactant. The multiple breath nitrogen washout method was used to measure the time pattern of nitrogen elimination from the lungs. VIH was evaluated by using both a compartmental lung model and a model-independent moment analysis. The two-compartment lung model was found to dominate before surfactant treatment, while a single-compartment model (implying homogeneous ventilation) fitted the washout data best 6 hours after Exosurf treatment (P < 0.01). The same pattern occurred 2 hours after Survanta administration. Moment analysis confirmed the reduction in VIH by both surfactants. This study supports the hypothesis that the improved oxygenation after surfactant treatment in infants with HMD results from a reduction in VIH and an increase in functional residual capacity (FRC).

We determined if surfactant treatment effect can be enhanced by mechanical volume recruitment during surfactant administration by measuring functional residual capacity, tidal volume, the alveolar portion of tidal volume, dynamic compliance of the respiratory system, a/A ratio, and PaCO2 by measuring before and after surfactant administration to rabbits with lung injury induced by airway lavage. There was improvement in all lung function indices when surfactant was given with volume recruitment, but when surfactant was given without volume recruitment, the only index to show significant improvement was a/A ratio of oxygenation. These results support the hypothesis that mechanical recruitment of terminal airspaces from a previously unventilated compartment will enhance the effectiveness of surfactant replacement by facilitating the distribution of instilled surfactant to this compartment.

I analyze the influence of the economic characteristics of origin area on trip duration for Mexican migrants in the United States. I argue that migrants from economically dynamic areas in Mexico with favorable opportunities for employment and small capital investment have a larger incentive to stay in the United States longer and to withstand the psychic costs of separation from family and friends than do migrants from economically stagnant areas in Mexico, where the productive uses of savings are severely limited. In line with this argument we should expect investment opportunities in migrants' origin areas to be associated positively with migrants' trip duration in the United States. To test this hypothesis I use individual- and household-level data on U.S. migration experience collected in 13 Mexican communities. Evidence from parametric hazards models supports the idea that economic characteristics of origin areas influence the motivations and strategies of Mexican migrants in the United States.

To investigate the possibility that susceptibility to bronchopulmonary dysplasia (BPD) is affected by genetic factors, we analyzed risk factors for BPD in 108 twin pairs of infants having birth weight < or = 1,500 g. When BPD occurred in a first born twin (n = 23), it also occurred in 65% (n = 15) of the second born twins, and when BPD did not occur in the first twin (n = 85), it only occurred in 8% (n = 7) of the second twins (crude odds ratio = 20.9). After adjusting for potentially significant risk factors including birth weight, gestational age, gender, diagnosis of hyaline membrane disease, pneumothorax, symptomatic patent ductus arteriosus, and year of admission, using multiple logistic regression on the entire database (1,872 admissions < or = 1,500 g), BPD status of a first twin remained a highly significant predictor of BPD in the second twin (adjusted odds ratio = 12.3, P < .001). Other factors including birth order of twins, twin gestation, inborn/outborn status, cesarean section delivery, 1- and 5-minute Apgar scores, maternal race, maternal diabetes, and antepartum corticosteroid treatment were not significant predictors of BPD. These results are consistent with genetic factors affecting the susceptibility of very low birth weight premature infants to BPD, but we cannot exclude the possibility that factors not included in our analysis are also involved.

The ventilatory effects of breath-by-breath measurements of airway occlusion pressure, i.e., airway pressure determined 100 ms after initiation of inspiration (P0.1) were evaluated in seven lambs studied sequentially between 7 and 28 days after birth. P0.1 was determined by computer-aided, on-line regression analysis of the inspiratory pressure versus time (dP/dt) by means of a pneumatic occlusion valve that allowed occlusion times to vary in proportion to respiratory rate. No significant changes were found in minute ventilation, tidal volume, respiratory rate or end-tidal CO2 concentration when the valve was operating as a oneway valve (opening pressure 0.02 kPa or 0.2 cmH2O) compared to when in occlusion mode [opening pressure 0.18-0.2 kPa or 1.8-2.0 cmH2O, mean occlusion time 44 (25) ms]. The calculated P0.1 values correlated well with those obtained from manual occlusions (r = 0.87, P < 0.0001). This new technique, which detects and discards irregular or non-linear (r < 0.95) inspiratory pressure profiles, enables breath-by-breath determinations of inspiratory drive in rapidly breathing lambs with minimal impact on respiratory pattern and ventilation.

A multiple-breath nitrogen washout system designed to measure lung volume in mechanically ventilated infants was validated by assessing three performance criteria: 1) accuracy of lung volume measurements in the presence of an endotracheal tube leak was assessed by comparing the measurements of functional residual capacity (FRC) in a mechanical lung model with and without airway leak; 2) in vivo accuracy was assessed in rabbits by comparing FRC measurements obtained by this system with measurements obtained by helium dilution; and 3) in vivo precision was assessed by analyzing measurements of FRC obtained in replicate measurements at different times in ventilator-dependent premature infants with hyaline membrane disease. The average difference between the measurements of FRC in a mechanical lung model with airway leak and without leak was 3.0 +/- 9.4% (mean +/- SD, P > 0.2), and no difference was greater than 20%. There was a significant correlation between the measurements of FRC in rabbits by nitrogen washout and by helium dilution (r = 0.93, P < 0.0001), and 65.4% of the paired measurements were within 20% of their average. The 95% limits of agreement within pairs of measurements by the two techniques ranged from -4.0 to + 6.5 mL/kg. FRC measured by helium dilution was slightly higher (1.3 +/- 2.7 mL/kg, P < 0.01) than FRC measured by nitrogen washout, and positive end-expiratory pressure was a significant predictor of this difference (P < 0.0001). The regression between the individual FRC measurements obtained in premature infants and the average of the other replicates was significant (r2 > 0.98, P < 0.0001). The coefficient of variation was 12.3%. These findings provide further validation of this multiple-breath nitrogen washout system for measuring FRC in premature infants during mechanical ventilation.

On-line intelligent monitoring, diagnosis, and control of dynamic systems such as patients in intensive care units necessitates the context-dependent acquisition, processing, analysis, and interpretation of large amounts of possibly noisy and incomplete data. The dynamic nature of the process also requires a continuous evaluation and adaptation of the monitoring strategy to respond to changes both in the monitored patient and in the monitoring equipment. Moreover, real-time constraints may imply data losses, the importance of which has to be minimized. This paper presents a computer architecture designed to accomplish these tasks. Its main components are a model and a data abstraction module. The model provides the system with a monitoring context related to the patient status. The data abstraction module relies on that information to adapt the monitoring strategy and provide the model with the necessary information. This paper focuses on the data abstraction module and its interaction with the model.

To describe the physiologic effects of surfactant treatment on gas exchange in human premature infants with hyaline membrane disease, functional residual capacity (FRC), tidal volume (VT), the alveolar portion of tidal volume (VA), alveolar ventilation (VA), nitrogen clearance index, effective breath fraction calculated as VA/VT, compliance of the respiratory system, and arterial oxygen and carbon dioxide tensions were measured in 17 patients before and 0.5, 2, and 6 h after the administration of a single dose of either a synthetic surfactant (SS), Exosurf (n = 10), or a bovine surfactant (BS), Survanta (n = 7). By 2 h, treatment with either BS or SS was followed by an increase in the arterial/alveolar ratio of PO2 (a/A) and in FRC (p < 0.01 for both a/A and FRC). The a/A and FRC improved sooner (p < 0.001) and to a greater extent (p < 0.01) after BS than after SS. Compliance of the respiratory system and VT were decreased after either BS or SS at 0.5 h (p < 0.01) and remained decreased after SS at 2 h (p < 0.01). There was no significant change in VA or VA after either BS or SS. Because FRC and a/A increased without an accompanying increase in VA, VA, or compliance of the respiratory system, we believe that the immediate increase in FRC in this study was caused by stabilization of gas exchange units already being ventilated in addition to recruitment of new units.(ABSTRACT TRUNCATED AT 250 WORDS)

YAQ is an ontology for model-based reasoning in physiologic domains. YAQ is based on a hybrid algebra of qualitative and numerical values, and is designed to benefit from the rich and ever-changing nature of information available in a critical care monitoring environment. The focus of the project is on diagnosis of clinical conditions, prediction of the effects of therapy, and therapy management assistance. Two models of diagnosis are implemented in YAQ: diagnosis based on associations, and model-based diagnosis. The ontology is applied to the domain of ventilator management in infants with respiratory distress syndrome (RDS). The article describes the diagnostic capabilities of YAQ, illustrates these concepts on examples taken from actual patient records, and reports the results of an evaluation of the diagnostic performance on the RDS/assisted ventilation domain model.

The incidence of bronchopulmonary dysplasia (BPD) increased from 10.6% in 1976 through 1980, to 21.7% (1981 through 1985), and to 32.9% (1986 through 1990) in very low birth weight neonates (1500 g or less) admitted to the Vanderbilt Neonatal Intensive Care Unit, while there was a concurrent decline in incidence of neonatal death (NEOD) during the same periods (26.4%, 18.3%, and 15.9%, respectively). Population changes in risk factors (birth weight, sex, race, location of birth, gestational age, diagnosis of hyaline membrane disease, and 5-minute Apgar score) over time do not account for this increase. To estimate the proportion of the increase in BPD attributable to the concurrent decline in NEOD during these periods, separate logistic regression models for NEOD and BPD were calculated from patients born during 1976 through 1985. These results were used to predict the expected number of cases of NEOD and BPD during 1986 through 1990, assuming that the adjusted incidence of NEOD and BPD remained constant from 1976 through 1985, to 1986 through 1990. The increase in the combined outcome, NEOD/BPD, over the three time periods (34.2%, 36.1%, and 43.5%) remained statistically significant after adjustment for the risk factors listed above. During 1986 through 1990, the predicted number of NEOD was 83 more than the number observed, while the predicted number with BPD was 115 less than the number observed. If all 83 averted cases of NEOD during 1986 through 1990 had developed BPD, then 83 (72%) of the 115 excess cases of BPD could be attributed to averted NEOD. The approximate 95% confidence interval for this estimate was 58% to 87%.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac-related deflections in thoracic electrical impedance have been thought to correlate sufficiently well with cardiac stroke volume to be used as the basis for a noninvasive estimation of cardiac output. To determine more precisely the physiological origin of the impedance deflection (DZ), we regarded right ventricular stroke volume (SVa) as the sum of two components: 1) that part of SVa responsible for the transient increment in pulmonary blood volume within a cardiac cycle, SVa-v and 2) the remaining part of SVa, (SVa-SVa-v). SVa-v was measured in lambs by integration of the difference between pulmonary arterial and pulmonary venous flow. SVa and its components were varied experimentally by opening and closing an aorticocaval shunt or by inflating and deflating a cuff implanted around the pulmonary artery. DZ was measured using a tetrapolar disk electrode system. Multivariate linear regression analysis revealed that SVa-v had a significant positive effect on DZ, and, at the same time, (SVa-SVa-v) had a significant negative effect on DZ. In the pulmonary artery occluder model, the positive effect of SVa-v dominated the opposing negative effect of (SVa - SVa-v) so that the net effect of SVa on DZ was positive and significant. In the aorticocaval shunt model, these effects opposed each other to the extent that there was no significant correlation between SVa and DZ. These results shed new light on the physiological origin of DZ. They also demonstrate that use of DZ to measure acute changes in cardiac output may yield misleading results. Changes or the lack of changes in thoracic electrical impedance do not necessarily reflect cardiac output status.

The incidence of major handicaps was studied in a selected high-risk population of 1919 very low birth weight (less than or equal to 1500 gm) infants born between 1976 and 1985. Seventy-four percent of these infants were discharged alive. We have handicap information on 632 infants who have been followed for up to 7 years of age; 462 were evaluated at 18 months or later. Patients lost to follow-up represent 55% of the eligible population, but inpatient morbidity factors were available for the entire population and were used to calculate synthetic estimates of handicap rates. The overall incidence of severe major handicaps at 18 months was 18.0% (83/462). Cerebral palsy was found in 7.6%, and 6.5% were mentally retarded (IQ less than or equal to 70). Severe retinopathy of prematurity was present in 5.5%, and 5.4% of the infants had neurosensory hearing loss. Thirty-one infants (6.7%) had more than one handicap, the most common combination being cerebral palsy and mental retardation. Outcome of infants grouped by 250 gm birth weight intervals was compared for two periods (1976 to 1980, and 1981 to 1985); the numbers of survivors in each birth weight group increased during the second period, especially in the 500 to 750 gm and the 751 to 1000 gm groups. The observed incidence of major handicaps decreased from the first 5-year period to the second 5-year period (p less than 0.001). The largest decreases in the observed proportion handicapped occurred in the two lowest birth weight groups. The incidence of multiple handicaps also dropped; again, the two lowest birth weight groups showed the largest decrease. We conclude that an increased survival rate of very low birth weight infants need not be associated with an increased incidence of major handicaps.

The cardiovascular response to administration of water to the larynx was studied in unanesthetized newborn lambs. The cardiovascular components of this laryngeal reflex response consisted of a decrease in heart rate associated with a decrease in cardiac output, an increase in systemic and pulmonary vascular resistance associated with increased blood pressure and blood flow redistribution. Blood flow decreased in carcass, kidneys, intestines, liver and spleen and increased in head, brain and heart. The magnitude of the separate components of the cardiovascular response correlated significantly with each other and with the respiratory response. Alpha-adrenergic blockade eliminated the blood pressure and blood flow redistribution response. Atropine blocked the heart rate response. The reflex-elicited decrease in cardiac output and the increase in systemic vascular resistance were augmented by beta-adrenergic blockade. The cardiovascular responses were diminished, but not abolished, when oxygenation and rhythmic ventilation were artificially maintained during laryngeal water stimulation. These results indicate the possible interaction with the arterial chemoreceptors, stimulated by the concomitant 26 torr decrease in arterial oxygen tension, as well as with the cessation of the pulmonary inflation reflex associated with the apnoea.

Right and left ventricular outputs, pulmonary and systemic blood flows, and blood flows in both directions through the ductus arteriosus were measured before and during positive-end-expiratory-pressure in 5 premature lambs with induced hyaline membrane disease. During positive-end-expiratory-pressure, right ventricular output increased in all lambs without any significant change in left ventricular output or pulmonary vascular resistance. Left-to-right ductus flow decreased in lambs which initially had large left-to-right ductus shunts. significant right-to-left ductus flow did not occur before or during positive-end-expiratory-pressure.

The administration of a single intravenous injection of indomethacin was followed by a major constrictive effect on the ductus in 36 of 42 very-low-birth-weight (less than or equal to 1000 gm) infants with symptomatic patent ductus arteriosus (PDA). In 26 of the 36 responders, the effect was sustained; symptomatic PDA recurred in the remaining 10. Infants who experienced a recurrence of symptomatic PDA had lower birth weights and had received indomethacin at an earlier postnatal age than did infants with a sustained effect. These results may be explained by differences in the production and clearance of prostaglandins or in the sensitivity of the ductus to prostaglandin effects between infants with a recurrence and infants with sustained constriction of PDA.

A combined pulsed and continuous Doppler instrument was used to assess flow velocities in an in vitro model designed to simulate small deeply lying arterial vessels. Diameters of the model vessels, depth under the transducers and the pulsatile flow patterns were chosen to simulate the corresponding conditions that can be expected when cerebral blood flow velocities are measured with this technique through the anterior fontanel in newborn infants. Computer analysis of the space average velocity signal from the pulsed Doppler mode, showed that the area under this curve, which corresponds to distance, was closely correlated to true flow over a wide range of flows in vessels of different diameters. This variable is suggested to be the closest estimate of true flow, when the diameter of the vessel under study cannot be accurately measured.

There appears to be an increase in the number of premature infants who survive treatment in neonatal intensive care units. Such an increase is expected to result in a greater number of children with developmental delays in a variety of dimensions, including auditory and psycholinguistic abilities. This report presents hearing and speech/language data on a sample of 266 high-risk infants. The data revealed that approximately one-third of the population exhibited hearing impairment and/or speech/language problems. The need for early identification and periodic assessment with this population is emphasized.

Extravascular lung water and vascular permeability-surface area products were measured with a multiple indicator dilution method in five unanaesthetized newborn lambs 2 to 7 h following delivery by Caesarean section at a gestational age of 135-142 days. The indicators used were 51Cr-labelled erythrocytes, [125I] albumin, [3H] water and [14C] urea. Post-mortem determination of extravascular lung water and dry bloodless lung weight were also performed. The results were compared with previously obtained data in unanaesthetized 3-5 days-old lambs and adult sheep. Normalized to dry lung weight, extravascular lung water by both techniques was significantly higher in lambs after Caesarean section than in either the 3-5 days-old lambs or the adult sheep (P less than 0.05). (Indicator values = 3.9 +/- 0.2 (SEM) ml/g for Caesarean section lambs, 3.1 +/- 0.3 for 3-5 days-old lambs and 3.3 +/- 0.5 for adult sheep; post-mortem values were 6.12 +/- 0.28 g/g for after Caesarean section lambs, 4.07 +/- 0.26 for 3-5 days old lambs and 4.03 +/- 0.17 for sheep). Vascular permeability-surface area product for [14C] urea, computed by a mathematical model, was significantly higher (P less than 0.05) in lambs after Caesarean section than in adult sheep (0.18 +/- 0.02 compared with 0.10 +/- 0.03). In 3-5 days-old lambs the value was 0.16 +/- 0.04. It is concluded that, when normalized to dry lung weight, lung following Caesarean section delivery near the end of gestation. Adult values for lung water have been reached by the age of 3-5 days.

Electrical impedance plethysmography was evaluated in lambs as a method of measuring tidal volume (VT). Over tidal volumes ranging from 15 to 414% of estimated dead space, and frequencies of 300 to 1000 breaths/min, correlation between VT measured by the impedance technique and VT measured by whole-body plethysmography was 0.98. Above 600 breaths/min, the correlation between the two methods was 0.94. Independent calibration of the impedance technique using a pneumotachograph at conventional rates of ventilation yielded absolute values of VT which closely corresponded to values obtained with the whole-body plethysmograph (slope = 1.05, intercept = 1.4 ml, r = 0.99). These results support the potential utility of impedance plethysmography in clinical applications of high frequency ventilation.

The effects of changes in carotid blood flow on intracranial blood flow velocities were examined in six newborn lambs under general anesthesia. Carotid blood flow was measured using electromagnetic flow cuffs. A combined continuous and pulsed Doppler instrument was used to measure intracranial blood flow velocities on the base of the skull through artificially created fontanels. Baseline carotid blood flow was 96 +/- 18 ml X min-1 (mean +/- SD) and increased by 58 +/- 13% following contralateral occlusion. A close correlation between changes in carotid blood flow and intracranial blood flow velocity was found (y = -6.28 + 3.72x, Sy = 182.3, Sy/x = 0.30, r = 0.89, p less than 0.001). The closest estimate of changes in blood flow to the brain was the temporal mean of the cross-sectional average velocity.

A model based on the course of 31 infants with uncomplicated hyaline membrane disease is described. Based on data collected over the first 12 hr of life, it predicts the course of an infant for the next 60 hr, and estimates the outcome in terms of length of oxygen requirement and assisted ventilation. For the construction of the model, right-to-left intra- and extra-pulmonary shunting, expressed as venous admixture, was considered as the principal mechanism of hypoxemia in hyaline membrane disease and mean applied proximal airway pressure was used to quantify management. The model provides an objective estimate of severity early in the course of disease, uses variables routinely available in an intensive care unit, and its use would strengthen the interpretation of clinical studies in which the comparability of experimental and control groups is critical.

A scoring system based on discriminant analysis was devised to predict, within 24 hours after birth, whether or not a premature infant will subsequently develop a symptomatic PDA. Five risk factors including birth weight, the diagnosis of hyaline membrane disease, intrauterine growth retardation, acute perinatal stress, and treatment with distending airway pressure were reduced to a discriminant score which separated infants with symptomatic PDA from infants without symptomatic PDA. Based on this score, the likelihood that an individual infant would later develop symptomatic PDA could be expressed as a probability function. When applied prospectively, this score predicted the correct outcome of 80% of infants in a test population. This predictive model should be useful in clinical trials and other applications requiring a quantitative expression of risk for developing symptomatic ductus shunting.

A modified impedence cardiographic technique was developed using a tetrapolar apnea monitor and minicomputer system. Evaluation of this technique in premature infants with and without symptomatic patent ductus arteriosus indicates that the magnitude of the cardiac-related deflection in the impedance signal is useful in the assessment of ductus shunting. Since the infant under study is involved only by the attachment of two double electrodes to the thorax, continuous assessment of ductur shunting is possible without disturbing routine care.