Bronchopulmonary dysplasia and neurodevelopmental outcome in extremely preterm neonates

We tested the hypothesis that the use of supplemental oxygen (sO(2)) at discharge from the NICU in extremely preterm neonates is associated with a greater risk of neurodevelopmental impairment (NDI) at 18 months corrected gestational age (CGA) than the risk of NDI of those neonates discharged in room air. Four hundred twenty-four charts were retrospectively reviewed from infants born at <27 weeks and transferred to Nationwide Children’s Hospital from December 1, 2004 to June 14, 2010. Use of sO(2) was evaluated on day of life (dol) 28, at 36 weeks post-menstrual age (PMA), and at discharge. Logistic regression was used to identify postnatal risk factors associated with sO(2) at discharge and NDI. At dol 28, 96 % of surviving patients received sO(2), and therefore had bronchopulmonary dysplasia (BPD) by definition from a National Institutes of Child Health and Human Development workshop. At 36 weeks PMA, 89 % continued on sO(2) (moderate/severe BPD), and at discharge, 74 % continued on sO(2). When factors associated with NDI were examined, the need for mechanical ventilation ≥28 days (adjOR = 3.21, p = 0.01), grade III–IV intraventricular hemorrhage (IVH) (adjOR = 4.61, p < 0.01), and discharge at >43 weeks PMA (adjOR = 2.12, p = 0.04) were the strongest predictors of NDI at 18 months CGA. There was no difference in Bayley Scales of Infant Development, third edition composite scores between patients with no/mild BPD and patients with moderate/severe BPD (cognitive p = 0.60, communication p = 0.53, motor p = 0.19) or those scores between patients on and off oxygen at discharge (cognitive p = 0.58, communication p = 0.70, motor p = 0.62). Conclusions: The need for sO(2) at discharge is not associated with an increased risk of NDI in these patients. The strongest predictors of poor neurodevelopmental outcome in this population were prolonged positive pressure support, grade III–IV IVH, and discharge at >43 weeks PMA

Intergenerational correlations in size at birth and the contribution of environmental factors: The Uppsala Birth Cohort Multigenerational Study, Sweden, 1915-2002.

Sizes at birth of parents and their children are known to be correlated, reflecting in part the influence of fetal and maternal genes. Sociodemographic factors, regarded as aspects of the shared environment across generations, would also be expected to contribute, but evidence is limited. In the present study, the authors aimed to quantify the role of the shared environment in explaining intergenerational correlations in birth weight and length by using data across 3 consecutive generations from the Uppsala Birth Cohort Multigenerational Study in Uppsala, Sweden. That study included birth and sociodemographic data on 7,657 singletons born in Uppsala in 1915-1929 (generation 1) and their grandchildren (generation 3). Standard regression and biometric models were used to study the correlations in size at birth of generation 1-generation 3 pairs. The data showed stronger correlations in maternal pairs than in paternal pairs for birth weight (0.125 vs. 0.096, P = 0.02) but not for birth length (0.097 vs. 0.093, P = 0.77). These correlations were not reduced by adjustment for sociodemographic factors in regression models. In contrast, significant shared-environment contributions to the intergenerational correlations were identified in biometric models, averaging 14% for both birth measures. These models assumed a common latent factor for the sociodemographic variables. The present results show that the shared environment moderately but significantly contributes to intergenerational correlations

Are published standards for haematological indices in pregnancy applicable across populations: an evaluation in healthy pregnant Jamaican women

<p>Abstract</p> <p>Background</p> <p>The haematological profile of the pregnant woman has an impact on the outcome of the pregnancy. Published guidelines indicate acceptable levels for haematological indices in pregnancy but they are population specific. Indicators of haemoglobin concentration are the most commonly utilized of the indices. These published international norms are used across populations, however, there is no evidence confirming their applicability to a population such as the Jamaican pregnant woman. This study was therefore undertaken with the intent of documenting the haematological profile of pregnant primigravid Jamaican women and comparing these to the established norms to determine whether the norms apply or whether there was a need to establish local norms.</p> <p>Methods</p> <p>This was a longitudinal study done on a cohort of 157 healthy primigravid women ages 15 to 25 and without anaemia, and who were recruited from the antenatal clinic of the University Hospital of the West Indies, Kingston, Jamaica. The haemoglobin concentration, packed cell volume, mean cell volume, mean cell haemoglobin, mean cell haemoglobin concentration, white blood cell count, red blood cell count and platelet count were measured on samples of blood obtained from each consenting participant during each of the three trimesters. The results were analysed using SPSS for windows (Version 11) and the data expressed as means ± S.D. Means were compared using the student's paired <it>t-test</it>. Comparison was then made with the international norms as recommended by the United States Center for Disease Control (1989). Ethical approval for this study was obtained from the University Hospital of the West Indies/University of the West Indies Ethics Committee.</p> <p>Results</p> <p>The results showed changes by trimester in all measured variables. For most of the indices the changes achieved levels of significance across trimesters. These changes were however in keeping with the expected physiological response in pregnancy and the values were similar to the published international norms.</p> <p>Conclusion</p> <p>The findings suggest that the international norms for haematological indices in pregnancy are applicable across populations and to the pregnant Jamaican primigravid woman. This finding may be reassuring to others with a similar population and stage of development as Jamaica.</p

Multiple Imputation Ensembles (MIE) for dealing with missing data

Missing data is a significant issue in many real-world datasets, yet there are no robust methods for dealing with it appropriately. In this paper, we propose a robust approach to dealing with missing data in classification problems: Multiple Imputation Ensembles (MIE). Our method integrates two approaches: multiple imputation and ensemble methods and compares two types of ensembles: bagging and stacking. We also propose a robust experimental set-up using 20 benchmark datasets from the UCI machine learning repository. For each dataset, we introduce increasing amounts of data Missing Completely at Random. Firstly, we use a number of single/multiple imputation methods to recover the missing values and then ensemble a number of different classifiers built on the imputed data. We assess the quality of the imputation by using dissimilarity measures. We also evaluate the MIE performance by comparing classification accuracy on the complete and imputed data. Furthermore, we use the accuracy of simple imputation as a benchmark for comparison. We find that our proposed approach combining multiple imputation with ensemble techniques outperform others, particularly as missing data increases

Prenatal DDT Exposure in Relation to Anthropometric and Pubertal Measures in Adolescent Males

DDT (dichlorodiphenyltrichloroethane), a pesticide once used widely in agriculture and now limited to public health use, remains a controversial chemical because of a combination of benefits and risks. DDT or its breakdown products are ubiquitous in the environment and in humans. Compounds in the DDT family have endocrine actions and have been associated with reproductive toxicity. A previous study reported associations between prenatal exposure to p,p′-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene] and increased height and weight in adolescent boys. We examined a group with higher exposures to see whether similar associations would occur. Our study group was 304 males born in Philadelphia in the early 1960s who had participated in a previous study. Anthropometric and pubertal measures from one to six visits during their adolescent years were available, as were stored maternal serum samples from pregnancy. We measured p,p′-DDE, p,p′-DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane], and o,p′-DDT [1,1,1-trichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)-ethane] in the maternal serum. Outcomes examined in the boys were height, ratio of sitting height to height, body mass index, triceps skinfold thickness, ratio of subscapular to the sum of triceps and subscapular skinfold thicknesses, skeletal age, serum testosterone, and serum dehydroepiandrosterone sulfate. No associations between prenatal exposure to any of the DDT compounds and any outcome measure were seen

In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide

<p>Abstract</p> <p>Background</p> <p>Hydrogen peroxide (H₂O₂) produced by vaginal lactobacilli is generally believed to protect against bacteria associated with bacterial vaginosis (BV), and strains of lactobacilli that can produce H₂O₂are being developed as vaginal probiotics. However, evidence that led to this belief was based in part on non-physiological conditions, antioxidant-free aerobic conditions selected to maximize both production and microbicidal activity of H₂O₂. Here we used conditions more like those <it>in vivo </it>to compare the effects of physiologically plausible concentrations of H₂O₂and lactic acid on a broad range of BV-associated bacteria and vaginal lactobacilli.</p> <p>Methods</p> <p>Anaerobic cultures of seventeen species of BV-associated bacteria and four species of vaginal lactobacilli were exposed to H₂O₂, lactic acid, or acetic acid at pH 7.0 and pH 4.5. After two hours, the remaining viable bacteria were enumerated by growth on agar media plates. The effect of vaginal fluid (VF) on the microbicidal activities of H₂O₂and lactic acid was also measured.</p> <p>Results</p> <p>Physiological concentrations of H₂O₂(< 100 μM) failed to inactivate any of the BV-associated bacteria tested, even in the presence of human myeloperoxidase (MPO) that increases the microbicidal activity of H₂O₂. At 10 mM, H₂O₂inactivated all four species of vaginal lactobacilli but only one of seventeen species of BV-associated bacteria. Moreover, the addition of just 1% vaginal fluid (VF) blocked the microbicidal activity of 1 M H₂O₂. In contrast, lactic acid at physiological concentrations (55-111 mM) and pH (4.5) inactivated all the BV-associated bacteria tested, and had no detectable effect on the vaginal lactobacilli. Also, the addition of 10% VF did not block the microbicidal activity of lactic acid.</p> <p>Conclusions</p> <p>Under optimal, anaerobic growth conditions, physiological concentrations of lactic acid inactivated BV-associated bacteria without affecting vaginal lactobacilli, whereas physiological concentrations of H₂O₂produced no detectable inactivation of either BV-associated bacteria or vaginal lactobacilli. Moreover, at very high concentrations, H₂O₂was more toxic to vaginal lactobacilli than to BV-associated bacteria. On the basis of these <it>in vitro </it>observations, we conclude that lactic acid, not H₂O₂, is likely to suppress BV-associated bacteria <it>in vivo</it>.</p

Lifetime studies of Mo/Si and Mo/Be multilayer coatings for extreme ultraviolet lithography

Extreme Ultraviolet Lithography (EUVL) is a candidate for future application by the semiconductor industry in the production of sub-100 nm feature sizes in integrated circuits. Using multilayer reflective coatings optimized at wavelengths ranging from 11 to 14 nm, EUVL represents a potential successor to currently existing optical lithography techniques. In order to assess lifetimes of the multilayer coatings under realistic conditions, a series of radiation stability tests has been performed. In each run a dose of EUV radiation equivalent to several months of lithographic operation was applied to Mo/Si and MO/Be multilayer coatings within a few days. Depending on the residual gas concentration in the vacuum environment, surface deposition of carbon during the exposure lead to losses in the multilayer reflectivity. However, in none of the experimental runs was structural damage within the bulk of the multilayers observed. Mo/Si multilayer coatings recovered their full original reflectivity after removal of the carbon layer by an ozone cleaning method. Auger depth profiling on MO/Be multilayers indicate that carbon penetrated into the Be top layer during illumination with high doses of EUV radiation. Subsequent ozone cleaning fully removed the carbon, but revealed enhanced oxidation of the area illuminated, which led to an irreversible loss in reflectance on the order of 1%. Keywords: Extreme ultraviolet (EUV) lithography, multilayer reflective coatings, radiation stability, surface contaminatio

Evaluating the Cellular Targets of Anti-4-1BB Agonist Antibody during Immunotherapy of a Pre-Established Tumor in Mice

Manipulation of the immune system represents a promising avenue for cancer therapy. Rational advances in immunotherapy of cancer will require an understanding of the precise correlates of protection. Agonistic antibodies against the tumor necrosis factor receptor family member 4-1BB are emerging as a promising tool in cancer therapy, with evidence that these antibodies expand both T cells as well as innate immune cells. Depletion studies have suggested that several cell types can play a role in these immunotherapeutic regimens, but do not reveal which cells must directly receive the 4-1BB signals for effective therapy.We show that re-activated memory T cells are superior to resting memory T cells in control of an 8-day pre-established E.G7 tumor in mice. We find that ex vivo activation of the memory T cells allows the activated effectors to continue to divide and enter the tumor, regardless of antigen-specificity; however, only antigen-specific reactivated memory T cells show any efficacy in tumor control. When agonistic anti-4-1BB antibody is combined with this optimized adoptive T cell therapy, 80% of mice survive and are fully protected from tumor rechallenge. Using 4-1BB-deficient mice and mixed bone marrow chimeras, we find that it is sufficient to have 4-1BB only on the endogenous host alphabeta T cells or only on the transferred T cells for the effects of anti-4-1BB to be realized. Conversely, although multiple immune cell types express 4-1BB and both T cells and APC expand during anti-4-1BB therapy, 4-1BB on cells other than alphabeta T cells is neither necessary nor sufficient for the effect of anti-4-1BB in this adoptive immunotherapy model.This study establishes alphabeta T cells rather than innate immune cells as the critical target in anti-4-1BB therapy of a pre-established tumor. The study also demonstrates that ex vivo activation of memory T cells prior to infusion allows antigen-specific tumor control without the need for reactivation of the memory T cells in the tumor

Boolean network simulations for life scientists

Modern life sciences research increasingly relies on computational solutions, from large scale data analyses to theoretical modeling. Within the theoretical models Boolean networks occupy an increasing role as they are eminently suited at mapping biological observations and hypotheses into a mathematical formalism. The conceptual underpinnings of Boolean modeling are very accessible even without a background in quantitative sciences, yet it allows life scientists to describe and explore a wide range of surprisingly complex phenomena. In this paper we provide a clear overview of the concepts used in Boolean simulations, present a software library that can perform these simulations based on simple text inputs and give three case studies. The large scale simulations in these case studies demonstrate the Boolean paradigms and their applicability as well as the advanced features and complex use cases that our software package allows. Our software is distributed via a liberal Open Source license and is freely accessible fro