Aerosol chemical composition and distribution during the Pacific Exploratory Mission (PEM) Tropics

Distributions of aerosol-associated soluble ions over much of the South Pacific were determined by sampling from the NASA DC-8 as part of the Pacific Exploratory Mission (PEM) Tropics campaign. The mixing ratios of all ionic species were surprisingly low throughout the free troposphere (2-12 km), despite the pervasive influence from biomass burning plumes advecting over the South Pacific from the west during PEM-Tropics. At the same time, the specific activity of 7Be frequently exceeded 1000 fCi m-3 through much of the depth of the troposphere. These distributions indicate that the plumes must have been efficiently scavenged by precipitation (removing the soluble ions), but that the scavenging must have occurred far upwind of the DC-8 sampling regions (otherwise 7Be activities would also have been low). This inference is supported by large enhancements of HNO3 and carboxylic acids in many of the plumes, as these soluble acidic gases would also be readily scavenged in any precipitation events. Decreasing mixing ratios of NH4 + with altitude in all South Pacific regions sampled provide support for recent suggestions that oceanic emissions of NH3 constitute a significant source far from continents. Our sampling below 2 km reaffirms the latitudinal pattern in the methylsulfonate/non-sea-salt sulfate (MSA/nss SO4 =) molar ratio established through surface-based and shipboard sampling, with values increasing from \u3c0.05 in the tropics to nearly 0.6 at 70°S. However, we also found very high values of this ratio (0.2-0.5) at 10 km altitude above the intertropical convergence zone near 10°N. It appears that wet convective pumping of dimethylsulfide from the tropical marine boundary layer is responsible for the high values of the MSA/nss SO4 = ratio in the tropical upper troposphere. This finding complicates use of this ratio to infer the zonal origin of biogenic S transported long distances. Copyright 1999 by the American Geophysical Union

Variants in the fetal genome near FLT1 are associated with risk of preeclampsia.

: Preeclampsia, which affects approximately 5% of pregnancies, is a leading cause of maternal and perinatal death. The causes of preeclampsia remain unclear, but there is evidence for inherited susceptibility. Genome-wide association studies (GWAS) have not identified maternal sequence variants of genome-wide significance that replicate in independent data sets. We report the first GWAS of offspring from preeclamptic pregnancies and discovery of the first genome-wide significant susceptibility locus (rs4769613; P = 5.4 × 10(-11)) in 4,380 cases and 310,238 controls. This locus is near the FLT1 gene encoding Fms-like tyrosine kinase 1, providing biological support, as a placental isoform of this protein (sFlt-1) is implicated in the pathology of preeclampsia. The association was strongest in offspring from pregnancies in which preeclampsia developed during late gestation and offspring birth weights exceeded the tenth centile. An additional nearby variant, rs12050029, associated with preeclampsia independently of rs4769613. The newly discovered locus may enhance understanding of the pathophysiology of preeclampsia and its subtypes.<br/

Maternal angiotensinogen (AGT) haplotypes, fetal renin (REN) haplotypes and risk of preeclampsia; estimation of gene-gene interaction from family-triad data

Background Preeclampsia is a debilitating disorder affecting approximately 3% of pregnant women in the Western world. Although inconclusive, current evidence suggests that the renin-angiotensin system may be involved in hypertension. Therefore, our objective was to determine whether the genes for placental renin (REN) and maternal angiotensinogen (AGT) interact to influence the risk of preeclampsia. Methods Three haplotype-tagging SNPs (htSNPs) covering REN (rs5705, rs1464818, and rs3795575) and another three covering AGT (rs2148582, rs2478545 and rs943580) were genotyped in 99 mother-father-child triads of preeclampsia pregnancies. We estimated relative risks (RR) conferred by maternal AGT and fetal REN haplotypes using HAPLIN, a statistical software designed to detect multi-marker transmission distortion among triads. To assess a combined effect of maternal AGT and fetal REN haplotypes, the preeclamptic triads were first stratified by presence/absence of maternal AGT haplotype C-T-A and tested for an effect of fetal REN across these strata. Results We found evidence that mothers carrying the most frequent AGT haplotype, C-T-A, had a reduced risk of preeclampsia (RR of 0.4, 95% CI = 0.2-0.8 for heterozygotes and 0.6, 95% CI = 0.2-1.5 for homozygotes). Mothers homozygous for AGT haplotypes t-c-g and C-c-g appeared to have a higher risk, but only the former was statistically significant. We found only weak evidence of an overall effect of fetal REN haplotypes and no support for our hypothesis that an effect of REN depended on whether the mother carried the C-T-A haplotype of AGT (p = 0.33). Conclusion Our findings indicate that the mother's AGT haplotypes affect her risk for developing preeclampsia. However, this risk is not influenced by fetal REN haplotypes.publishedVersio

The red-sky enigma over Svalbard in December 2002

On 6 December 2002, during winter darkness, an extraordinary event occurred in the sky, as viewed from Longyearbyen (78° N, 15° E), Svalbard, Norway. At 07:30 UT the southeast sky was surprisingly lit up in a deep red colour. The light increased in intensity and spread out across the sky, and at 10:00 UT the illumination was observed to reach the zenith. The event died out at about 12:30 UT. Spectral measurements from the Auroral Station in Adventdalen confirm that the light was scattered sunlight. Even though the Sun was between 11.8 and 14.6deg below the horizon during the event, the measured intensities of scattered light on the southern horizon from the scanning photometers coincided with the rise and setting of the Sun. Calculations of actual heights, including refraction and atmospheric screening, indicate that the event most likely was scattered solar light from a target below the horizon. This is also confirmed by the OSIRIS instrument on board the Odin satellite. The deduced height profile indicates that the scattering target is located 18–23km up in the stratosphere at a latitude close to 73–75° N, southeast of Longyearbyen. The temperatures in this region were found to be low enough for Polar Stratospheric Clouds (PSC) to be formed. The target was also identified as PSC by the LIDAR systems at the Koldewey Station in Ny-Ålesund (79° N, 12° E). The event was most likely caused by solar illuminated type II Polar Stratospheric Clouds that scattered light towards Svalbard. Two types of scenarios are presented to explain how light is scattered.publishedVersio

An EPIC predictor of gestational age and its application to newborns conceived by assisted reproductive technologies

Background Gestational age is a useful proxy for assessing developmental maturity, but correct estimation of gestational age is difficult using clinical measures. DNA methylation at birth has proven to be an accurate predictor of gestational age. Previous predictors of epigenetic gestational age were based on DNA methylation data from the Illumina HumanMethylation 27 K or 450 K array, which have subsequently been replaced by the Illumina MethylationEPIC 850 K array (EPIC). Our aims here were to build an epigenetic gestational age clock specific for the EPIC array and to evaluate its precision and accuracy using the embryo transfer date of newborns from the largest EPIC-derived dataset to date on assisted reproductive technologies (ART). Methods We built an epigenetic gestational age clock using Lasso regression trained on 755 randomly selected non-ART newborns from the Norwegian Study of Assisted Reproductive Technologies (START)-a substudy of the Norwegian Mother, Father, and Child Cohort Study (MoBa). For the ART-conceived newborns, the START dataset had detailed information on the embryo transfer date and the specific ART procedure used for conception. The predicted gestational age was compared to clinically estimated gestational age in 200 non-ART and 838 ART newborns using MM-type robust regression. The performance of the clock was compared to previously published gestational age clocks in an independent replication sample of 148 newborns from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restrictions (PREDO) study-a prospective pregnancy cohort of Finnish women. Results Our new epigenetic gestational age clock showed higher precision and accuracy in predicting gestational age than previous gestational age clocks (R-2 = 0.724, median absolute deviation (MAD) = 3.14 days). Restricting the analysis to CpGs shared between 450 K and EPIC did not reduce the precision of the clock. Furthermore, validating the clock on ART newborns with known embryo transfer date confirmed that DNA methylation is an accurate predictor of gestational age (R-2 = 0.767, MAD = 3.7 days). Conclusions We present the first EPIC-based predictor of gestational age and demonstrate its robustness and precision in ART and non-ART newborns. As more datasets are being generated on the EPIC platform, this clock will be valuable in studies using gestational age to assess neonatal development.Peer reviewe

Candidate gene analysis of spontaneous preterm delivery: New insights from re-analysis of a case-control study using case-parent triads and control-mother dyads

<p>Abstract</p> <p>Background</p> <p>Spontaneous preterm delivery (PTD) has a multifactorial etiology with evidence of a genetic contribution to its pathogenesis. A number of candidate gene case-control studies have been performed on spontaneous PTD, but the results have been inconsistent, and do not fully assess the role of how two genotypes can impact outcome. To elucidate this latter point we re-analyzed data from a previously published case-control candidate gene study, using a case-parent triad design and a hybrid design combining case-parent triads and control-mother dyads. These methods offer a robust approach to genetic association studies for PTD compared to traditional case-control designs.</p> <p>Methods</p> <p>The study participants were obtained from the Norwegian Mother and Child Cohort Study (MoBa). A total of 196 case triads and 211 control dyads were selected for the analysis. A case-parent triad design as well as a hybrid design was used to analyze 1,326 SNPs from 159 candidate genes. We compared our results to those from a previous case-control study on the same samples. Haplotypes were analyzed using a sliding window of three SNPs and a pathway analysis was performed to gain biological insight into the pathophysiology of preterm delivery.</p> <p>Results</p> <p>The most consistent significant fetal gene across all analyses was COL5A2. The functionally similar COL5A1 was significant when combining fetal and maternal genotypes. PON1 was significant with analytical approaches for single locus association of fetal genes alone, but was possibly confounded by maternal effects. Focal adhesion (hsa04510), Cell Communication (hsa01430) and ECM receptor interaction (hsa04512) were the most constant significant pathways.</p> <p>Conclusion</p> <p>This study suggests a fetal association of COL5A2 and a combined fetal-maternal association of COL5A1 with spontaneous PTD. In addition, the pathway analysis implied interactions of genes affecting cell communication and extracellular matrix.</p

Determination of the efficacy and side-effect profile of lower doses of intrathecal morphine in patients undergoing total knee arthroplasty

<p>Abstract</p> <p>Background</p> <p>Intrathecal (IT) morphine provides excellent post-operative analgesia, but causes multiple side effects including nausea and vomiting (PONV), pruritus and respiratory depression, particularly at higher doses. The lowest effective dose of spinal morphine in patients undergoing total knee arthroplasty is not known.</p> <p>Methods</p> <p>We evaluated the analgesic efficacy and side effect profile of 100 – 300 μg IT morphine in patients undergoing elective total knee replacement in this prospective, randomized, controlled, double-blind study. Sixty patients over the age of 60 undergoing elective knee arthroplasty were enrolled. Patients were randomized to receive spinal anaesthesia with 15 mg Bupivacaine and IT morphine in three groups: (i) 100 μg; (ii) 200 μg; and (iii) 300 μg.</p> <p>Results</p> <p>Both 200 μg and 300 μg IT morphine provided comparable levels of postoperative analgesia. However, patients that received 100 μg had greater pain postoperatively, with higher pain scores and a greater requirement for supplemental morphine. There were no differences between groups with regard to PONV, pruritus, sedation, respiratory depression or urinary retention.</p> <p>Conclusion</p> <p>Both 200 μg and 300 μg provided comparable postoperative analgesia, which was superior to that provided by 100 μg IT morphine in patients undergoing total knee arthroplasty. Based on these findings, we recommend that 200 μg IT morphine be used in these patients.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier NCT00695045</p

State-Specific Trends in Preterm Delivery: Are Rates Really Declining Among Non-Hispanic African Americans Across the United States?

Objectives : This study sought to examine state-specific trends in preterm delivery rates among non-Hispanic African Americans and to assess whether these rates are influenced by misclassification of gestational age. Methods : The sample population consisted of singleton non-Hispanic White and non-Hispanic African–American infants born in 1991 and 2001 to U.S. resident mothers. For both time periods, state-specific and national preterm delivery rates were calculated for all infants, stratified by infant race/ethnicity. Next, birth-weight distributions within strata of gestational age were studied to explore possible misclassifications of gestational age. Lastly, state-specific and national preterm delivery rates among infants who weighed less than 2,500 g were separately computed. Results: National analyses showed that the frequency of preterm delivery increased by 15.8% among non-Hispanic Whites but declined by 10.3% among non-Hispanic African Americans over the same period. For both subgroups, a bimodal distribution of birth weights was apparent among preterm births at 28–31 weeks of gestation. The second peak with its cluster of normal-weight infants was more prominent among non-Hispanic African Americans in 1991 than in 2001. After excluding preterm infants who weighed 2,500 g or more, the national trends persisted. State-specific analyses showed that preterm delivery rates increased for both subgroups in 13 states during this period. Of these 13, 6 states had a number of non-Hispanic African–American births classified as preterm that were apparently term births mistakenly assigned short gestational ages. Such misclassification was more frequent in 1991 than in 2001 and inflated 1991 rates. Conclusion : There is heterogeneity in state-specific preterm delivery rates. Such differences are often overlooked when aggregate results are presented.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45321/1/10995_2005_Article_32.pd

X-Linked Genes and Risk of Orofacial Clefts: Evidence from Two Population-Based Studies in Scandinavia

Background: Orofacial clefts are common birth defects of complex etiology, with an excess of males among babies with cleft lip and palate, and an excess of females among those with cleft palate only. Although genes on the X chromosome have been implicated in clefting, there has been no association analysis of X-linked markers. Methodology/Principal Findings: We added new functionalities in the HAPLIN statistical software to enable association analysis of X-linked markers and an exploration of various causal scenarios relevant to orofacial clefts. Genotypes for 48 SNPs in 18 candidate genes on the X chromosome were analyzed in two population-based samples from Scandinavia (562 Norwegian and 235 Danish case-parent triads). For haplotype analysis, we used a sliding-window approach and assessed isolated cleft lip with or without cleft palate (iCL/P) separately from isolated cleft palate only (iCPO). We tested three statistical models in HAPLIN, allowing for: i) the same relative risk in males and females, ii) sex-specific relative risks, and iii) X-inactivation in females. We found weak but consistent associations with the oral-facial-digital syndrome 1 (OFD1) gene (formerly known as CXORF5) in the Danish iCL/P samples across all models, but not in the Norwegian iCL/P samples. In sex-specific analyses, the association with OFD1 was in male cases only. No analyses showed associations with iCPO in either the Norwegian or the Danish sample. Conclusions: The association of OFD1 with iCL/P is plausible given the biological relevance of this gene. However, the lack of replication in the Norwegian samples highlights the need to verify these preliminary findings in other large datasets. More generally, the novel analytic methods presented here are widely applicable to investigations of the role of X-linked genes in complex traits