Menoci: lightweight extensible web portal enhancing data management for biomedical research projects.

BACKGROUND: Biomedical research projects deal with data management requirements from multiple sources like funding agencies' guidelines, publisher policies, discipline best practices, and their own users' needs. We describe functional and quality requirements based on many years of experience implementing data management for the CRC 1002 and CRC 1190. A fully equipped data management software should improve documentation of experiments and materials, enable data storage and sharing according to the FAIR Guiding Principles while maximizing usability, information security, as well as software sustainability and reusability. RESULTS: We introduce the modular web portal software menoci for data collection, experiment documentation, data publication, sharing, and preservation in biomedical research projects. Menoci modules are based on the Drupal content management system which enables lightweight deployment and setup, and creates the possibility to combine research data management with a customisable project home page or collaboration platform. CONCLUSIONS: Management of research data and digital research artefacts is transforming from individual researcher or groups best practices towards project- or organisation-wide service infrastructures. To enable and support this structural transformation process, a vital ecosystem of open source software tools is needed. Menoci is a contribution to this ecosystem of research data management tools that is specifically designed to support biomedical research projects.

Chronic Toxicity of 4-Nonylphenol to Two Unionid Mussels in Water-Only Exposures.

Limited studies indicate that mussels are generally insensitive to organic chemicals; however, these studies were conducted in acute or short-term exposures, and little is known about the chronic sensitivity of mussels to organic chemicals. We evaluated the chronic (28 days) toxicity of 4-nonylphenol (4-NP) to two commonly tested species of mussels: fatmucket (Lampsilis siliquoidea) and rainbow mussel (Villosa iris). By the end of the 28 days chronic exposures, mean survival was ≥93% in all treatments, but the mean dry weight and biomass of mussels at the highest exposure concentrations were significantly reduced relative to the control. The 20% effect concentrations were similar between the two species. When compared to all other tested species, fatmucket and rainbow mussels are among the top four most sensitive species to 4-NP. However, U.S. Environmental Protection Agency chronic water quality criterion of 6.6 µg 4-NP/L should protect the two mussel species.

Integrated Data Repository Toolkit (IDRT). A Suite of Programs to Facilitate Health Analytics on Heterogeneous Medical Data.

BACKGROUND: In recent years, research data warehouses moved increasingly into the focus of interest of medical research. Nevertheless, there are only a few center-independent infrastructure solutions available. They aim to provide a consolidated view on medical data from various sources such as clinical trials, electronic health records, epidemiological registries or longitudinal cohorts. The i2b2 framework is a well-established solution for such repositories, but it lacks support for importing and integrating clinical data and metadata. OBJECTIVES: The goal of this project was to develop a platform for easy integration and administration of data from heterogeneous sources, to provide capabilities for linking them to medical terminologies and to allow for transforming and mapping of data streams for user-specific views. METHODS: A suite of three tools has been developed: the i2b2 Wizard for simplifying administration of i2b2, the IDRT Import and Mapping Tool for loading clinical data from various formats like CSV, SQL, CDISC ODM or biobanks and the IDRT i2b2 Web Client Plugin for advanced export options. The Import and Mapping Tool also includes an ontology editor for rearranging and mapping patient data and structures as well as annotating clinical data with medical terminologies, primarily those used in Germany (ICD-10-GM, OPS, ICD-O, etc.). RESULTS: With the three tools functional, new i2b2-based research projects can be created, populated and customized to researcher's needs in a few hours. Amalgamating data and metadata from different databases can be managed easily. With regards to data privacy a pseudonymization service can be plugged in. Using common ontologies and reference terminologies rather than project-specific ones leads to a consistent understanding of the data semantics. CONCLUSIONS: i2b2's promise is to enable clinical researchers to devise and test new hypothesis even without a deep knowledge in statistical programing. The approach presented here has been tested in a number of scenarios with millions of observations and tens of thousands of patients. Initially mostly observant, trained researchers were able to construct new analyses on their own. Early feedback indicates that timely and extensive access to their "own" data is appreciated most, but it is also lowering the barrier for other tasks, for instance checking data quality and completeness (missing data, wrong coding).

Cocaine exposure is associated with subtle compromises of infants' and mothers' social-emotional behavior and dyadic features of their interaction in the face-to-face still-face paradigm.

Prenatal cocaine and opiate exposure are thought to subtly compromise social and emotional development. The authors observed a large sample of 236 cocaine-exposed and 459 nonexposed infants (49 were opiate exposed and 646 nonexposed) with their mothers in the face-to-face still-face paradigm. Infant and maternal behaviors were microanalytically coded. No opiate-exposure effects were detected. However, mothers of cocaine-exposed infants showed more negative engagement than other mothers. The cocaine-exposed dyads also showed higher overall levels of mismatched engagement states than other dyads, including more negative engagement when the infants were in states of neutral engagement. Infants exposed to heavier levels of cocaine showed more passive-withdrawn negative engagement and engaged in more negative affective matching with their mothers than other infants. Although effect sizes were small, cocaine exposure, especially heavy cocaine exposure, was associated with subtly negative interchanges, which may have a cumulative impact on infants' later development and their relationships with their mothers.

Cebocephalus associated with trisomy 13-15 mosaicism.

A case of cebocephalus occurred in association with a 10% mosaicism of trisomy 13-15. Both parents of the affected child had normal karyotypes. Cebocephalus has been associated with abnormal chromosomes such as a deletion of the short arm of chromosome 18 as well as the trisomy 13-15.

Microangiopathic hemolytic anemia and thrombocytopenia in a neonate associated with a large placental chorioangioma.

The case of an infant born in association with a large chorioangioma of the placenta is presented. The maternal complications of polyhydramnios, preeclampsia, and premature labor are those described in the "syndrome" of a chorioangioma. The immediate neonatal course was unusually complicated by severe microangiopathic anemia with persistent thrombocytopenia and hemolysis which required three exchange blood transfusions. The relationship between the neonatal complications and the placental tumor is discussed in terms of possible pathophysiologic mechanisms.

Tactile/kinesthetic stimulation effects on preterm neonates.

Tactile/kinesthetic stimulation was given to 20 preterm neonates (mean gestational age, 31 weeks; mean birth weight, 1,280 g; mean time in neonatal intensive care unit, 20 days) during transitional ("grower") nursery care, and their growth, sleep-wake behavior, and Brazelton scale performance was compared with a group of 20 control neonates. The tactile/kinesthetic stimulation consisted of body stroking and passive movements of the limbs for three, 15-minute periods per day for a 10 days. The stimulated neonates averaged a 47% greater weight gain per day (mean 25 g v 17 g), were more active and alert during sleep/wake behavior observations, and showed more mature habituation, orientation, motor, and range of state behavior on the Brazelton scale than control infants. Finally, their hospital stay was 6 days shorter, yielding a cost savings of approximately $3,000 per infant. These data suggest that tactile/kinesthetic stimulation may be a cost effective way of facilitating growth and behavioral organization even in very small preterm neonates.

A decreased incidence of necrotizing enterocolitis after prenatal glucocorticoid therapy.

In a large multicentered, collaborative randomized and blinded trial utilizing antenatal corticosteroids, the goals included determining the effectiveness of these agents in accelerating lung maturation, as well as monitoring any short-term or long-term adverse effects of this treatment on the parturient, fetus, and/or infant. More than 100 specific items, pertaining to diagnoses, complications, and outcomes were recorded for the 696 mothers enrolled in the study and their 745 infants. A significantly decreased incidence of necrotizing enterocolitis (P = .002) was found in the infants treated with steroids. The possibility of accelerated intestinal maturation induced by antenatal maternal steroid therapy exists. This treatment regimen is particularly attractive as adverse aspects of steroid therapy at the dosage utilized have not been demonstrated.

Persistent pulmonary hypertension of the newborn in the era before nitric oxide: practice variation and outcomes.

OBJECTIVES: In the era before widespread use of inhaled nitric oxide, to determine the prevalence of persistent pulmonary hypertension (PPHN) in a multicenter cohort, demographic descriptors of the population, treatments used, the outcomes of those treatments, and variation in practice among centers. STUDY DESIGN: A total of 385 neonates who received >/=50% inspired oxygen and/or mechanical ventilation and had documented evidence of PPHN (2D echocardiogram or preductal or postductal oxygen difference) were tracked from admission at 12 Level III neonatal intensive care units. Demographics, treatments, and outcomes were documented. RESULTS: The prevalence of PPHN was 1.9 per 1000 live births (based on 71 558 inborns) with a wide variation observed among centers (.43-6.82 per 1000 live births). Neonates with PPHN were admitted to the Level III neonatal intensive care units at a mean of 12 hours of age (standard deviation: 19 hours). Wide variations in the use of all treatments studied were found at the centers. Hyperventilation was used in 65% overall but centers ranged from 33% to 92%, and continuous infusion of alkali was used in 75% overall, with a range of 27% to 93% of neonates. Other frequently used treatments included sedation (94%; range: 77%-100%), paralysis (73%; range: 33%-98%), and inotrope administration (84%; range: 46%-100%). Vasodilator drugs, primarily tolazoline, were used in 39% (range: 13%-81%) of neonates. Despite the wide variation in practice, there was no significant difference in mortality among centers. Mortality was 11% (range: 4%-33%). No specific therapy was clearly associated with a reduction in mortality. To determine whether the therapies were equivalent, neonates treated with hyperventilation were compared with those treated with alkali infusion. Hyperventilation reduced the risk of extracorporeal membrane oxygenation without increasing the use of oxygen at 28 days of age. In contrast, the use of alkali infusion was associated with increased use of extracorporeal membrane oxygenation (odds ratio: 5.03, compared with those treated with hyperventilation) and an increased use of oxygen at 28 days of age. CONCLUSIONS: Hyperventilation and alkali infusion are not equivalent in their outcomes in neonates with PPHN. Randomized trials are needed to evaluate the role of these common therapies.

Longitudinal growth of hospitalized very low birth weight infants.

BACKGROUND: The interpretation of growth rates for very low birth weight infants is obscured by limited data, recent changes in perinatal care, and the uncertain effects of multiple therapies. OBJECTIVES: To develop contemporary postnatal growth curves for very low birth weight preterm infants and to relate growth velocity to birth weight, nutritional practices, fetal growth status (small- or appropriate-for-gestational-age), and major neonatal morbidities (chronic lung disease, nosocomial infection or late-onset infection, severe intraventricular hemorrhage, and necrotizing enterocolitis). DESIGN: Large, multicenter, prospective cohort study. METHODS: Growth was prospectively assessed for 1660 infants with birth weights between 501 to 1500 g admitted by 24 hours of age to 1 of the 12 National Institute of Child Health and Human Development Neonatal Research Network centers between August 31, 1994 and August 9, 1995. Infants were included if they survived >7 days (168 hours) and were free of major congenital anomalies. Anthropometric measures (body weight, length, head circumference, and midarm circumference) were performed from birth until discharge, transfer, death, age 120 days, or a body weight of 2000 g. To obtain representative data, nutritional practices were not altered by the study protocol. RESULTS: Postnatal growth curves suitable for clinical and research use were constructed for body weight, length, head circumference, and midarm circumference. Once birth weight was regained, weight gain (14.4-16.1 g/kg/d) approximated intrauterine rates. However, at hospital discharge, most infants born between 24 and 29 weeks of gestation had not achieved the median birth weight of the reference fetus at the same postmenstrual age. Gestational age, race, and gender had no effect on growth within 100-g birth weight strata. Appropriate-for-gestational age infants who survived to hospital discharge without developing chronic lung disease, severe intraventricular hemorrhage, necrotizing enterocolitis, or late onset-sepsis gained weight faster than comparable infants with those morbidities. More rapid weight gain was also associated with a shorter duration of parenteral nutrition providing at least 75% of the total daily fluid volume, an earlier age at the initiation of enteral feedings, and an earlier age at achievement of full enteral feedings. CONCLUSIONS: These growth curves may be used to better understand postnatal growth, to help identify infants developing illnesses affecting growth, and to aid in the design of future research. They should not be taken as optimal. Randomized clinical trials should be performed to evaluate whether different nutritional management practices will permit birth weight to be regained earlier and result in more rapid growth, more appropriate body composition, and improved short- and long-term outcomes.

Incidence, presenting features, risk factors and significance of late onset septicemia in very low birth weight infants. The National Institute of Child Health and Human Development Neonatal Research Network.

BACKGROUND: Septicemia is a major antecedent of morbidity and mortality in very low birth weight (501- to 1500-g) infants. Our purpose was to determine prospectively the incidence, clinical presentation, laboratory features, risk factors, morbidity and mortality associated with late onset septicemia in infants 501 to 1500 g. METHODS: Clinical data were prospectively collected for 2416 infants enrolled in a multicenter trial to determine the efficacy of intravenous immunoglobulin in preventing nosocomial infections. Septicemia was confirmed by positive blood culture in 395 symptomatic infants. Multivariate analyses of factors associated with septicemia were performed. RESULTS: Sixteen percent of VLBW infants developed septicemia at a median age of 17 days. Factors associated with septicemia by logistic regression included male gender, lower gestational age and birth weight and decreased baseline serum IgG concentrations. Increasing apnea (55%), feeding intolerance, abdominal distension or guaiac-positive stools (43%), increased respiratory support (29%), lethargy and hypotonia (23%) were the dominant presenting features of septicemia. An abnormal white blood cell count (46%), unexplained metabolic acidosis (11%) and hyperglycemia (10%) were the most common laboratory indicators. Septicemic infants, compared with nonsepticemic infants, had significantly increased mortality (21% vs. 9%), longer hospital stay (98 vs. 58 days) and more serious morbidity, including severe intraventricular hemorrhage, bronchopulmonary dysplasia and increased ventilator days (P < 0.001). CONCLUSIONS: Late onset septicemia is common in very low birth weight infants, and the rate is inversely proportional to gestational age and birth weight. Septicemia is more common in males and those with low initial serum IgG values. A set of clinical signs (apnea, bradycardia, etc.) and laboratory values (leukocytosis, immature white blood cells and neutropenia) increase the probability of late onset sepsis, but they have poor positive predictive value.

Central and autonomic nervous systems' signs associated with in utero exposure to cocaine/opiates.

In summary, we found that the prevalence of CNS/ANS signs was significantly higher in the infants exposed to cocaine and/or opiates than in nonexposed infants. However, the prevalence of a large number of these signs was less than 5%. The prevalence rates of these signs are lower when exposure involved cocaine only; thus, their assessment has limited clinical utility.

Prenatal and perinatal risk and protective factors for neonatal intracranial hemorrhage. National Institute of Child Health and Human Development Neonatal Research Network.

OBJECTIVE: To identify prenatal and perinatal risk and protective factors for grade III and IV intracranial hemorrhage (ICH) in 4795 singleton infants (weight, < or = 1500 g). METHOD: Prenatal and perinatal risk and protective factors for ICH were examined initially by univariate analysis and adjusted for year of birth, followed by multivariate logistic regression analysis that adjusted simultaneously for the effects of year of birth and prenatal and perinatal characteristics. SETTING: Seven tertiary care neonatal-perinatal centers. RESULTS: By univariate analysis, African-American race, prenatal care, older maternal age, hypertension or preeclampsia, antenatal steroid administration, cesarean section delivery, increasing birth weight, increasing gestational age, and female gender of the infant were protective prenatal or perinatal factors. Antepartum hemorrhage, the presence of labor, and breech presentation were perinatal factors that were associated with an increased risk of ICH. By using staged logistic regression, a model of combined prenatal and perinatal characteristics that influenced grade III and IV ICH was developed. Significant protective factors against ICH included a complete course of antenatal steroid therapy, African-American maternal race, female gender of the infant, hypertension or preeclampsia with no antepartum hemorrhage, increasing gestational age, and increasing birth weight. CONCLUSION: Antenatal steroid administration is a therapeutic intervention that is associated with a decreased risk for neonatal grade III and IV ICH.

Central and autonomic system signs with in utero drug exposure.

AIMS: To determine risk for central nervous system/autonomic nervous system (CNS/ANS) signs following in utero cocaine and opiate exposure. METHODS: A multisite study was designed to determine outcomes of in utero cocaine and opiate exposure. A total of 11 811 maternal/infant dyads were enrolled. Drug exposed (EXP) infants were identified by maternal self report of cocaine or opiate use or by meconium testing. Of 1185 EXP, meconium analysis confirmed exposure in 717 to cocaine (CO) only, 100 to opiates (OP), and 92 to opiates plus cocaine (OP+CO); 276 had insufficient or no meconium to confirm maternal self report. Negative exposure history was confirmed in 7442 by meconium analysis and unconfirmed in 3184. Examiners masked to exposure status, assessed each enrolled infant. Using generalised estimating equations, adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated for manifesting a constellation of CNS/ANS outcomes and for each sign associated with cocaine and opiate exposure. RESULTS: Prevalence of CNS/ANS signs was low in CO, and highest in OP+CO. Signs were significantly related to one another. After controlling for confounders, CO was associated with increased risk of manifesting a constellation of CNS/ANS outcomes, OR (95% CI): 1.7 (1.2 to 2.2), independent of OP effect, OR (95% CI): 2.8 (2.1 to 3.7). OP+CO had additive effects, OR (95% CI): 4.8 (2.9 to 7.9). Smoking also increased the risk for the constellation of CNS/ANS signs, OR (95% CI) of 1.3 (1.04 to 1.55) and 1.4 (1.2 to 1.6), respectively, for use of less than half a pack per day and half a pack per day or more. CONCLUSION: Cocaine or opiate exposure increases the risk for manifesting a constellation of CNS/ANS outcomes.

Prenatal drug exposure and maternal and infant feeding behaviour.

OBJECTIVE: To evaluate feeding difficulties and maternal behaviour during a feeding session with 1 month old infants prenatally exposed to cocaine and/or opiates. METHODS: The study is part of the maternal lifestyle study, which recruited 11 811 subjects at four urban hospitals, then followed 1388 from 1 to 36 months of age. Exposure to cocaine and opiates was determined by maternal interview and meconium assay. At the 1 month clinic visit, biological mothers were videotaped while bottle feeding their infants. This sample included 364 exposed to cocaine, 45 exposed to opiates, 31 exposed to both drugs, and 588 matched comparison infants. Mothers were mostly black, high school educated, and on public assistance. Videotapes were coded without knowledge of exposure status for frequency, duration and quality of infant sucking, arousal, feeding problems, and maternal feeding activity and interaction. RESULTS: No cocaine effects were found on infant feeding measures, but cocaine-using mothers were less flexible (6.29 v 6.50), less engaged (5.77 v 6.22), and had shorter feeding sessions (638 v 683 seconds). Opiate exposed infants showed prolonged sucking bursts (29 v 20 seconds), fewer pauses (1.6 v 2.2 per minute), more feeding problems (0.55 v 0.38), and increased arousal (2.59 v 2.39). Their mothers showed increased activity (30 v 22), independent of their infants' feeding problems. CONCLUSIONS: Previous concerns about feeding behaviour in cocaine exposed infants may reflect the quality of the feeding interaction rather than infant feeding problems related to prenatal exposure. However, opiate exposed infants and their mothers both contributed to increased arousal and heightened feeding behaviour.

Sex differences in outcomes of very low birthweight infants: the newborn male disadvantage.

OBJECTIVE: To determine the differences in short term outcome of very low birthweight infants attributable to sex. METHODS: Boys and girls weighing 501-1500 g admitted to the 12 centres of the National Institute of Child Health and Human Development Neonatal Research Network were compared. Maternal information and perinatal data were collected from hospital records. Infant outcome was recorded at discharge, at 120 days of age if the infant was still in hospital, or at death. Best obstetric estimate based on the last menstrual period, standard obstetric factors, and ultrasound were used to assign gestational age in completed weeks. Data were collected on a cohort that included 3356 boys and 3382 girls, representing all inborn births from 1 May 1991 to 31 December 1993. RESULTS: Mortality for boys was 22% and that for girls 15%. The prenatal and perinatal data indicate few differences between the sex groups, except that boys were less likely to have been exposed to antenatal steroids (odds ratio (OR) = 0.80) and were less stable after birth, as reflected in a higher percentage with lower Apgar scores at one and five minutes and the need for physical and pharmacological assistance. In particular, boys were more likely to have been intubated (OR = 1.16) and to have received resuscitation medication (OR = 1.40). Boys had a higher risk (OR > 1.00) for most adverse neonatal outcomes. Although pulmonary morbidity predominated, intracranial haemorrhage and urinary tract infection were also more common. CONCLUSIONS: Relative differences in short term morbidity and mortality persist between the sexes.

Effect of antenatal dexamethasone on neonatal leukocyte count.

The leukocyte count and differential white blood cell count during the first hour of life was determined in 164 neonates born of mothers receiving antenatal steroids and compared to 171 neonates of mothers randomly assigned to a placebo group. A leukemoid reaction (greater than 40,000 WBC/mm3) was seen only once each in the neonates born of placebo or steroid treated mothers. In addition, maternal steroid treatment had no general effect, except in a small subgroup of neonates born 3 to 7 days after the mother had been treated with 20 mg dexamethasone, where the total leukocyte and the absolute neutrophil counts were higher than the placebo group and other subgroups.

Perinatal effects of prenatal drug exposure. Neonatal aspects.

When substance-exposure issues are intermingled with other high-risk-factors like low socioeconomic status, poor nutrition, lack of appropriate stimulation, neglect, abuse, and violence, it becomes impossible to isolate the various contributions to an infant or child's failure to thrive. Many of these issues are societal and beyond the individual's direct control. Drug exposure is not. Both maternal abuse and environmental contamination can be addressed by the individual. Deliberate exposure of an infant or child to drugs is a form of child abuse that is preventable. Information and education are, it is hoped, the keys to effective intervention.

The Bayley Scales of Infant Development. II: Where to start?

This study examines whether the Bayley Scales of Infant Development-Second Edition (Bayley II) Mental Scale scores vary on the basis of which item set is considered the starting point of an infant's assessment. The Bayley II was administered to 78 12-month-old infants by certified examiners beginning with the 12-month age item set. A second certified examiner then administered 10 additional items that completed the 11-month and 13-month age item sets. Of the 78 infants tested, 73 (94%) met basal and ceiling criteria in all three item sets. Three separate Mental Developmental Index (MDI) scores were calculated using 12-month norms for each subject, which were based on the raw scores generated from the 11-, 12-, and 13-month age item sets. Scores calculated on the 11-month set were significantly lower than those on the 12-month set, which were in turn significantly lower than those on the 13-month set. When tested on the 11-month instead of on the 12-month item set, twice as many infants received lower than normal (< 85) MDI scores, indicating an impact on referability decisions. Minor adjustments in administration of the Bayley II, such as those based on assumptions regarding an infant's current level of functioning, significantly affect infant test scores and eligibility for follow-up services. Standardized use of this test should minimize variability in test scores.

Immunoassay and GC-MS procedures for the analysis of drugs of abuse in meconium.

The analysis of meconium specimens for metabolites of substances of abuse is a relatively accurate method for the detection of fetal exposure to drugs. Most of the methods reported in the literature before the early 1990s relied on radioimmunoassays. The purpose of this study was to develop and validate methods for meconium sample preparation for the screening and gas chromatography-mass spectrometry (GC-MS) confirmation of meconium extracts for cannabinoids, cocaine, opiates, amphetamines, and phencyclidine. EMIT and TDx immunoassays were evaluated as screening methods. The sample preparation method developed for screening included extraction and purification prior to analysis. Cutoff levels were administratively set at 20 ng/g for 11-nor-delta9-THC-9-COOH (THCCOOH) and phencyclidine and at 200 ng/g for benzoylecgonine, morphine, and amphetamines, although lower levels could be detected in meconium using the EMIT-ETS system. Ninety-five meconium specimens were subjected to the screening procedure with GC-MS confirmation of presumptive positives. In addition, 30 (40 for cocaine) meconium specimens were subjected to GC-MS analysis for all analytes regardless of the screening results to determine the false-negative rate, if any, of the immunoassay. Although there were no false negatives detected, the GC-MS confirmation rate for the immunoassay-positive specimens was generally low, ranging from 0% for amphetamines to 75% for opiates. The lowest rate of confirmed positives was found with the cannabinoids, suggesting that tetrahydrocannabinol (THC) metabolites other than free 11-nor-9-carboxy-delta9-THC may be major contributors to the immunoassay response in meconium.