Foundation for Blood Research

Scarborough, ME, United States

Foundation for Blood Research

Scarborough, ME, United States

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Madan J.,Dartmouth Hitchcock Medical Center | Goodman E.,Floating Hospital for Children | Allan W.,Foundation for Blood Research | Dammann O.,Hannover Medical School | Dammann O.,Childrens Hospital
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2010

Objective. To study maternal obesity as a risk factor for preterm delivery. Methods. Maine State Birth Records Database from 1996 through 2006 was evaluated to investigate obese pregnant women compared with normal weight women regarding risk for preterm delivery. Multiple risk factors and outcomes were studied in univariable and multivariable models. Results. Among 58,112 pregnant women, 8% (n = 4653) gave birth to preterm infants. Univariable analyses revealed a relationship between obesity and increased risk of prematurity. In multivariable regressions, the most important intermediate variable appears to be gestational hypertension/preeclampsia. Conclusions. As maternal body mass index increases in pregnancy, the risk of preterm delivery and other maternal complications increases. The obesity-prematurity relationship is complex, with hypertensive disorders of pregnancy playing a crucial role. More detailed analyses of causal pathways are warranted. © 2010 Informa UK Ltd.


Craig W.Y.,Foundation for Blood Research | Palomaki G.E.,Brown University | Shackleton C.H.L.,Childrens Hospital Oakland Research Institute | Marcos J.,Institute Municipal dInvestigacio Medica | Haddow J.E.,Brown University
Prenatal Diagnosis | Year: 2010

Objective: Estimate steroid sulfatase deficiency (STSD) prevalence among California's racial/ethnic groups using data from a previous study focused on prenatal detection of Smith-Lemli-Opitz syndrome (SLOS). SLOS and STSD both have low maternal serum unconjugated estriol (uE3) levels. Methods: Prevalence was estimated using three steps: listing clinically identified cases; modeling STSD frequency at three uE3 intervals using diagnostic urine steroid measurements; applying this model to determine frequency in pregnancies not providing urine. Results: Overall, 2151 of 777 088 pregnancies (0.28%) were screen positive; 1379 of these were explained and excluded. Fifty-four cases were diagnosed clinically among 707 remaining pregnancies with a male fetus. Urine steroid testing identified 74 additional STSD cases: 66 (89.2%) at uE3 values <0.15 MoM, 8 (10.8%) at 0.15-0.20 MoM, and 0 (0%) at >0.20 MoM. Modeling estimated 107.5 STSD cases among 370 pregnancies without urine samples. In males, STSD prevalence was highest among non-Hispanic Whites (1 : 1230) compared to Hispanics (1 : 1620) and Asians (1 : 1790), but differences were not significant. No STSD pregnancies were found among 65 screen positive Black women. Conclusion: The overall prevalence estimate of 1 : 1500 males is consistent with published estimates and is reasonable for counseling, except among Black pregnancies where no reliable estimate could be made. Copyright © 2010 John Wiley & Sons, Ltd.


Lee I.,Santa Fe Institute | Martin F.,University of Massachusetts Lowell | Denner J.,ETR Associates | Coulter B.,Missouri Botanical Garden | And 4 more authors.
ACM Inroads | Year: 2011

been described as the use of abstraction, automation, and analysis in problem-solving [3]. We examine how these ways of thinking take shape for middle and high school youth in a set of NSF-supported programs. We discuss opportunities and challenges in both in-school and after-school contexts. Based on these observations, we present a "use-modify-create" framework, representing three phases of students' cognitive and practical activity in computational thinking. We recommend continued investment in the development of CT-rich learning environments, in educators who can facilitate their use, and in research on the broader value of computational thinking. © 2011 ACM.


Haddow J.E.,Brown University | Haddow J.E.,Savjani Institute for Health Research | Craig W.Y.,Foundation for Blood Research | Palomaki G.E.,Brown University | And 8 more authors.
Thyroid | Year: 2013

Background: Among euthyroid pregnant women in a large clinical trial, free thyroxine (FT4) measurements below the 2.5th centile were associated with a 17 lb higher weight (2.9 kg/m2) than in the overall study population. We explore this relationship further. Methods: Among 9351 women with second trimester thyrotropin (TSH) measurements between 1st and 98th centiles, we examine: (i) the weight/FT4 relationship; (ii) percentages of women in three weight categories at each FT4 decile; (iii) FT4 concentrations in three weight categories at each TSH decile; and (iv) impact of adjusting FT4 for weight-in the reference group and in 190 additional women with elevated TSH measurements. Results: FT4 values decrease steadily as weight increases (p<0.0001 by ANOVA) among women in the reference group (TSH 0.05-3.8 IU/L). TSH follows no consistent pattern with weight. When stratified into weight tertiles, 48% of women at the lowest FT4 decile are heavy; the percentage decreases steadily to 22% at the highest FT4 decile. Median FT4 is lowest in heaviest women regardless of the TSH level. In the reference group, weight adjustment reduces overall variance by 2.9%. Fewer FT4 measurements are at either extreme (below the 5th FT4 centile: 4.8% before adjustment, 4.7% after adjustment; above the 95th FT4 centile: 5.0% and 4.7%, respectively). Adjustment places more light weight women and fewer heavy women below the 5th FT4 centile; the converse above the 95th centile. Between TSH 3.8 and 5 IU/L, the FT4 percentage below the 5th FT4 centile is not elevated (3.8% before adjustment, 3.1% after adjustment). Percentage of FT4 values above the 95th centile, however, is lower (1.5% before adjustment, 0.8% after adjustment). Above TSH 5 IU/L, 25% of women have FT4 values below the 5th FT4 centile; weight adjustment raises this to 30%; no FT4 values remain above the 95th FT4 centile. Conclusions: During early pregnancy, TSH values are not associated with weight, unlike nonpregnant adults. Lower average FT4 values among heavy women at all TSH deciles partially explain interindividual differences in FT4 reference ranges. The continuous reciprocal relationship between weight and FT4 explains lower FT4 with higher weight. Weight adjustment refines FT4 interpretation. © 2013, Mary Ann Liebert, Inc.


Craig W.Y.,Foundation for Blood Research | Allan W.C.,Foundation for Blood Research | Kloza E.M.,Foundation for Blood Research | Kloza E.M.,Brown University | And 6 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: Lower neurocognitive development scores at age 2 yr have been reported in association with euthyroid hypothyroxinemia during early pregnancy. Objective: The objective of this study was to further explore this association with euthyroid hypothyroxinemia during early pregnancy. Design: This was an observational, nested case-control study. Setting: The study was conducted at physician offices and prenatal clinics throughout Maine. Study Subjects: Between May 2004 and March 2006, TSH was measured in 5734 women in conjunction with second-trimester Down syndrome screening. After completion of pregnancy, free T 4 was measured in stored second-trimester sera from euthyroid women (TSH 0.1-3.5 mIU/ml; n = 5560). Women with free T 4 at the third centile or less (n = 99) were matched with women whose free T 4 was at the 10th to the 90th centile (n = 99). Interventions: There were no interventions. Main Outcome Measure: Bayley Scales of Infant Development (BSID III) were administered to the 198 offspring at age 2 yr. Scores for cognitive, language, and motor development were compared between matched pairs of offspring from the two groups before and after correcting for relevant variables. Results: Unadjusted BSID-III scores (cognitive, language,and motor) were lower by about 3% at age 2 yr among offspring of 98 hypothyroxinemic women (cases), reaching borderline significance for cognitive and motor scores. After adjustment for gestational age, the child's age at testing, maternal weight, and education, all differences diminished and became nonsignificant. Scores less than 85 were more frequent among case children but did not reach statistical significance (P = 0.14). Conclusions: Isolated hypothyroxinemia during the second trimester is not associated with significantly lower BSID-III scores at age 2 yr, compared with scores for offspring of matched euthyroxinemic women. Copyright © 2012 by The Endocrine Society.


Haddow J.E.,Brown University | Haddow J.E.,Savjani Institute for Health Research | Craig W.Y.,Foundation for Blood Research | Neveux L.M.,Brown University | And 8 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Context: Lower birth weight has been reported in conjunction with high maternal free T4 (FT4) in euthyroid pregnancies, raising concerns for suboptimal outcomes. Objective: The objective of the study was to explore the relationships between high maternal FT4 and pregnancy complications in euthyroidwomenand to further examine the relationshipsamong maternal size, FT4, and birth weight. Design: This was an observational multicenter cohort study. Setting: The study was conducted at prenatal clinics. Study Subjects: A total of 9209 euthyroid women with singleton pregnancies participated in the study. Interventions: There were no interventions. Main Outcome Measures: Relationships between second-trimester high maternal FT4 and pregnancy/ delivery complications and, among FT4, maternal weight and birth weight were measured. Results: Women in the highest FT4 quintile are younger and weigh less than women in quintiles 1-4; gestational diabetes and preeclampsia occur less often (P = < .001, P < .001, P < .001, and P=.05, respectively). Lowest median birth weight occursamongwomenin the highest FT4 quintile (P = < .001), but deliveries less than 37 weeks' gestation are not increased. Labor/delivery complications do not differ by FT4 quintile. Restricting analyses to maternal weight-adjusted smallfor- gestational-age deliveries yields similar results, except for preeclampsia. In the highest maternal weight decile, adjusted median birth weight is 266 g higher (8.3%) than in the lowest weight decile; adjusted median FT4 is 0.91 pmol/L lower (6.8%). Among women in the highest FT4 decile, adjusted median birth weight is 46 g lower (1.3%) than in the lowest FT4 decile. All three relationships are statistically significant (P < .001, P < .001, and P = .004, respectively). Conclusions: Lower median birth weight among euthyroid women with high FT4 is not associated with adverse pregnancy outcomes. Further investigation is indicated to determine how the variations in thyroid hormone concentration influence birth weight. © 2014 by the Endocrine Society.


Chen Q.,University of Pittsburgh | Reis S.E.,University of Pittsburgh | Kammerer C.,University of Pittsburgh | Craig W.,Foundation for Blood Research | And 7 more authors.
Journal of Lipid Research | Year: 2011

Atherosclerosis is the major cause of coronary artery disease (CAD), and oxidized LDL (oxLDL) is believed to play a key role in the initiation of the atherosclerotic process. Recent studies show that inflammation and autoimmune reactions are also relevant in atherosclerosis. In this study, we examined the association of antibodies against oxLDL (anti-oxLDL) with the severity of CAD in 558 Women's Ischemia Syndrome Evaluation (WISE) study samples (465 whites; 93 blacks) determined by coronary stenosis (<20%, 20%-49%, >50% stenosis). We also examined the relationship of anti-oxLDL with serum lipid levels and nine candidate genes including APOE, APOH, APOA5, LPL, LRP1, HL, CETP, PON1, and OLR1. IgM anti-oxLDL levels were significantly higher in the >20% stenosis group than in the ∩20% stenosis group in whites (0.69 ± 0.02 vs. 0.64 ± 0.01, respectively; P = 0.02). IgM anti-oxLDL levels correlated significantly with total cholesterol (r2 = 0.01; P = 0.03) and LDL cholesterol (r2 = 0.017; P = 0.004) in whites. Multiple regression analysis revealed a suggestive association of LPL/S447X single-nucleotide polymorphism (SNP) with both IgG antioxLDL (P = 0.02) and IgM anti-oxLDL (P = 0.07), as well as between IgM anti-oxLDL and the OLR1/3′UTR SNP (P = 0.020). Our data suggest that higher IgM anti-oxLDL levels may provide protection against coronary stenosis and that genetic variation in some candidate genes are determinants of anti-oxLDL levels. Copyright © 2011 by the American Society for Biochemistry and Molecular Biology, Inc.


Craig W.Y.,Foundation for Blood Research | Ledue T.B.,Foundation for Blood Research
Clinical Chemistry and Laboratory Medicine | Year: 2012

Background: Anti-extractable nuclear antigen antibodies (anti-ENA) have diagnostic significance in systemic rheumatic disease (SRD). Methods: Anti-ENA were tested in 1685/30,196 sera that were submitted sequentially for antinuclear antibody (ANA) testing. Frequency was stratified by ANA titer and pattern, by referral source, by submitted diagnosis and by patient age and sex. Results: Anti-ENA frequency increased with ANA titer (7.3 at <3243.3 at <1024). Anti-histone (11.6) and anti-SSA/SSB (13.9) were the most frequent finding with a homo\xadgeneous pattern; anti-SSA/SSB (39.7) and anti-RNP/anti-Sm (37.7) were the most frequent finding with a speckled pattern. Sera with speckled, multiple and homogenous ANA patterns accounted for 92.6 of positive anti-ENA findings. At ANA titer <256, 29.2 of these sera were tested for anti-ENA, of which 41.2 were positive; frequency was higher with an accompanying diagnosis of SRD (53.5 vs. 36.5, p<0.004 by χ2-test) but not with referral by rheumatologists (43.5 vs. 35.9) and did not differ by patient age or sex. Conclusions: Reflexive anti-ENA testing may be helpful among sera with ANA titer <256 and homogeneous, speckled or multiple patterns, irrespective of referral source or accompanying diagnosis. Further work is needed to evaluate the clinical impact of this protocol. © 2012 by Walter de Gruyter Berlin Boston.


Ledue T.B.,Foundation for Blood Research | Collins M.F.,Foundation for Blood Research
Journal of Clinical Laboratory Analysis | Year: 2011

Many laboratories rely on dedicated nephelometers and turbidimeters for the measurement of serum proteins. There are, however, a number of chemistry analyzers that offer open channel configurations for end-user applications. We developed and validated 14 human serum protein assays (α1-antitrypsin, α2-macroglobulin, albumin, apolipoproteins AI and B, complement components 3 and 4, haptoglobin, immunoglobulins A, G, and M, orosomucoid, transferrin, and transthyretin) on the Roche cobas® c 501. We obtained excellent precision at low, normal, and high physiologic concentrations of each protein (within-run imprecision CVs ≤2.5%, total imprecision CVs ≤3.6%). Linearity for each method was within 5% of the expected value throughout the calibration range, and method comparison studies to commercial assays from Roche or Siemens were in good agreement (r>0.975). We observed no significant interference from bilirubin (up to 414mg/l), hemoglobin (up to 8.9g/l), triglyceride (up to 28g/l), or rheumatoid factor (up to 3,930IU/ml). Calibration was stable for at least 14 days. The instrument's small reaction cell allowed us to conserve nearly 60% of our specimen and reagent volume compared with our previous system. These newly developed assays provide precise and accurate results with high throughput, but without the associated cost of a dedicated instrument. © 2011 Wiley-Liss, Inc.


Craig W.Y.,Foundation for Blood Research | Ledue T.B.,Foundation for Blood Research
Clinical Chemistry and Laboratory Medicine | Year: 2011

Background: We examined the relationship between antinuclear antibody (ANA) data and the presence of anti-double stranded DNA antibodies (anti-dsDNA). Methods: De-identified demographic, ANA and anti-dsDNA data were available for 30,196 individuals aged ≥20 years, whose sera were submitted sequentially to our laboratory. When multiple sera were received for the same subject, data from the earliest sample were used. Anti-dsDNA frequency was stratified by ANA titer and pattern, sample referral source, and by the patient's age, gender, and diagnosis. Results: For sera with ANA titer ≥256 and an accompanying diagnosis of systemic lupus erythematosus, anti-dsDNA frequency was 53.7%, 35.3%, and 37.5% for homogeneous, speckled, or multiple ANA patterns, respectively. Among remaining sera with ANA titer ≥256, anti-dsDNA frequency was highest for the homogeneous pattern (15.9%). Anti-dsDNA frequency was three-fold higher among sera submitted by rheumatologists compared with other providers. However, its relative distribution by ANA pattern and titer was similar between these groups. Patient age and gender had no significant effect on anti-dsDNA frequency after ANA data were taken into account. Conclusions: ANA pattern and titer, together with the diagnosis submitted with the serum sample, can be used to guide decisions for reflexive anti-dsDNA testing in a clinical laboratory setting. © 2011 by Walter de Gruyter Berlin Boston.

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