Real-Time Minimization of Mechanical Specific Energy with Multivariable Extremum Seeking

Drilling more efficiently and with less non-productive time (NPT) is one of the key enablers to reduce field development costs. In this work, we investigate the application of a data-driven optimization method called extremum seeking (ES) to achieve more efficient and safe drilling through automatic real-time minimization of the mechanical specific energy (MSE). The ES algorithm gathers information about the current downhole conditions by performing small tests with the applied weight on bit (WOB) and drill string rotational rate (RPM) while drilling and automatically implements optimization actions based on the test results. The ES method does not require an a priori model of the drilling process and can thus be applied even in instances when sufficiently accurate drilling models are not available. The proposed algorithm can handle various drilling constraints related to drilling dysfunctions and hardware limitations. The algorithm’s performance is demonstrated by simulations, where the algorithm successfully finds and maintains the optimal WOB and RPM while adhering to drilling constraints in various settings. The simulations show that the ES method is able to track changes in the optimal WOB and RPM corresponding to changes in the drilled formation. As demonstrated in the simulation scenarios, the overall improvements in rate of penetration (ROP) can be up to 20–170%, depending on the initial guess of the optimal WOB and RPM obtained from e.g., a drill-off test or a potentially inaccurate model. The presented algorithm is supplied with specific design choices and tuning considerations that facilitate its simple and efficient use in drilling applications.publishedVersio

Prediction of gestational age based on genome-wide differentially methylated regions

BACKGROUND: We explored the association between gestational age and cord blood DNA methylation at birth and whether DNA methylation could be effective in predicting gestational age due to limitations with the presently used methods. We used data from the Norwegian Mother and Child Birth Cohort study (MoBa) with Illumina HumanMethylation450 data measured for 1753 newborns in two batches: MoBa 1, n = 1068; and MoBa 2, n = 685. Gestational age was computed using both ultrasound and the last menstrual period. We evaluated associations between DNA methylation and gestational age and developed a statistical model for predicting gestational age using MoBa 1 for training and MoBa 2 for predictions. The prediction model was additionally used to compare ultrasound and last menstrual period-based gestational age predictions. Furthermore, both CpGs and associated genes detected in the training models were compared to those detected in a published prediction model for chronological age. RESULTS: There were 5474 CpGs associated with ultrasound gestational age after adjustment for a set of covariates, including estimated cell type proportions, and Bonferroni-correction for multiple testing. Our model predicted ultrasound gestational age more accurately than it predicted last menstrual period gestational age. CONCLUSIONS: DNA methylation at birth appears to be a good predictor of gestational age. Ultrasound gestational age is more strongly associated with methylation than last menstrual period gestational age. The CpGs linked with our gestational age prediction model, and their associated genes, differed substantially from the corresponding CpGs and genes associated with a chronological age prediction model. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-016-1063-4) contains supplementary material, which is available to authorized users

Pre-eclampsia and childhood asthma

Studies of pre-eclampsia and childhood asthma are conflicting, and none have performed a formal mediation analysis of preterm birth.We examined the association between pre-eclampsia and asthma at 7 years using national registries, including all births in Norway from 1999 to 2006 (n=406 907), and a subsample of children in the Norwegian Mother and Child Cohort Study (MoBa) (n=45 028) using log-linear regression. We performed a mediation analysis of preterm birth, and a sibling comparison to evaluate unobserved confounding.There was a positive association between pre-eclampsia and asthma in the registry study, with an adjusted relative risk of 1.31 (95% CI 1.22–1.41), but not in MoBa, which had an adjusted relative risk of 1.19 (95% CI 0.99–1.44). The odds ratios for the direct effect not mediated through preterm birth and the indirect effect in the registry linkage were 1.19 (95% CI 1.10–1.29) and 1.12 (95% CI 1.11–1.14), respectively. The sibling comparison indicated no association between pre-eclampsia and asthma (adjusted OR 1.07, 95% CI 0.87–1.33).In this large study, which used different datasets and analytic approaches, there was little evidence for an association between pre-eclampsia and childhood asthma. The association was weak and largely explained by pre-term birth and confounders shared by siblings.</jats:p

Early life growth and associations with lung function and bronchial hyperresponsiveness at 11-years of age

Low birthweight and being born small-for-gestational age (SGA) are linked to asthma and impaired lung function. Particularly, poor intrauterine growth followed by rapid catch-up growth during childhood may predispose for respiratory disease. Bronchial hyperresponsiveness (BHR) is an essential feature of asthma, but how foetal and early childhood growth are associated with BHR is less studied. Our hypothesis was that children born SGA or with accelerated early life growth have increased BHR and altered lung function at 11-years of age. We studied the associations between SGA and early childhood growth with lung function and BHR at 11-years of age in a subgroup of 468 children from the Norwegian Mother, Father and Child Cohort Study (MoBa), and included data from the Medical Birth Registry of Norway (MBRN). Weight at 6 months of age was positively associated with forced vital capacity (adjusted Beta: 0.121; 95% Confidence interval: 0.023, 0.219) and negatively associated with the ratio of forced expiratory flow in first second/forced vital capacity (−0.204; −0.317, −0.091) at 11-years of age. Similar patterns were found for weight at 36 months and for change in weight from birth to 6 months of age. SGA or other various variables of early childhood growth were not associated with BHR at 11-years of age. Early life growth was associated with an obstructive lung function pattern, but not with BHR in 11-year old children. Foetal growth restriction or weight gain during early childhood do not seem to be important risk factors for subsequent BHR in children.acceptedVersio

Airway symptoms and atopy in young children prescribed asthma medications:A large-scale cohort study

Diagnosing asthma and deciding treatment are difficult in young children. An inappropriate and too high prescription rate of inhaled corticosteroids (ICS) is suggested, but how airway symptoms are associated with prescriptions of asthma medication is less known. We studied how strongly wheeze, lower respiratory tract infections (LRTI), and atopic diseases are associated with dispensing of asthma medications during early childhood. We used data from the Norwegian Mother and Child Cohort Study and the Norwegian Prescription Database at four age‐intervals (0‐6, 6‐18, 18‐36 months, and 3‐7 years). Primary outcomes were dispensed asthma medications (no medication, short‐acting β‐2 agonist, or ICS). Relative risks (RRs) and average attributable fractions (AAFs) were estimated. Both wheeze and LRTI were positively associated with both medication groups (0‐6 months: no data on wheeze). The RRs and AAFs were higher for wheeze than LRTI. For ICS, the AAFs (95% CI) for wheeze vs LRTI were: 6 to 18 months: 69.2 (67.2, 71.2)% vs 10.4 (9.0, 11.8)%, 18 to 36 months: 33.0 (30.5, 35.5)% vs 10.0 (8.0, 12.0)%, and 3 to 7 years: 33.7 (31.0, 36.5)% vs 1.2 (0.5, 1.9)%. Except at 3 to 7 years of age, the AAFs were lower for atopic diseases than for LRTI and wheeze. Atopic diseases modified the associations between wheeze and ICS at 18 to 36 months and between LRTI or wheeze and ICS at 3 to 7 years. In conclusion, both wheeze and LRTI were associated with prescriptions of asthma medications in young children, with the strongest associations seen for wheeze. Atopic diseases contributed to these associations only in the oldest age groups.publishedVersio

25-hydroxyvitamin D in pregnancy and genome wide cord blood DNA methylation in two pregnancy cohorts (MoBa and ALSPAC)

The aim of the study was to investigate whether maternal mid-pregnancy 25-hydroxyvitamin D concentrations are associated with cord blood DNA methylation. DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip, and maternal plasma 25-hydroxyvitamin D was measured in 819 mothers/newborn pairs participating in the Norwegian Mother and Child Cohort (MoBa) and 597 mothers/newborn pairs participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Across 473,731CpG DNA methylation sites in cord blood DNA, none were strongly associated with maternal 25-hydroxyvitamin D after adjusting for multiple tests (false discovery rate (FDR) > 0.5; 473,731 tests). A meta-analysis of the results from both cohorts, using the Fisher method for combining p-values, also did not strengthen findings (FDR > 0.2). Further exploration of a set of CpG sites in the proximity of four a priori defined candidate genes (CYP24A1, CYP27B1, CYP27A1 and CYP2R1) did not result in any associations with FDR < 0.05 (56 tests). In this large genome wide assessment of the potential influence of maternal vitamin D status on DNA methylation, we did not find any convincing associations in 1416 newborns. If true associations do exist, their identification might require much larger consortium studies, expanded genomic coverage, investigation of alternative cell types or measurements of 25-hydroxyvitamin D at different gestational time points

Maternal history of miscarriages and measures of fertility in relation to childhood asthma

Background: it remains unclear what underlies the greater risk of asthma reported among children conceived by assisted reproductive technologies (art). Objective: Our aim was to clarify the role of parental subfertility and unmeasured confounding on the association between art and childhood asthma, and to examine the possibility for common mechanisms underlying parental subfertility and miscarriages influencing asthma pathogenesis. Methods: We used data from national norwegian health registries (n=474 402) and the norwegian Mother and child cohort Study (MoBa) (n=75 797). We used log-linear regression to estimate overall associations, and fixed-effects logistic regression to estimate associations within siblings. Results: ART offspring had greater asthma risk, the adjusted relative risk (arr) was 1.20 (95% ci 1.09 to 1.32) in the registry-based cohort, and 1.42 (95% ci 1.14 to 1.76) in MoBa. the sibling analysis yielded similar associations, although the ci included the null value. the elevated asthma risk among art offspring was attenuated when they were compared with spontaneously conceived offspring with time to conception >12 months, arr 1.22 (95% ci 0.95 to 1.57). asthma risk also increased with maternal history of early miscarriages (≤12 weeks), with an arr of 1.07 (95% ci 1.03 to 1.11) for one, arr 1.18 (95% ci 1.10 to 1.26) for two and arr 1.24 (95% ci 1.12 to 1.37) for three or more. Conclusion: Our findings indicate that both parental subfertility and characteristics related to the art procedure itself might increase offspring asthma risk, although this needs to be confirmed in future studies, and further suggest that common mechanisms underlying parental subfertility and recurrent miscarriages might influence offspring asthma pathogenesis