Estimating community-level costs of preterm birth.

OBJECTIVES: To develop generalizable methods for estimating the economic impact of preterm birth at the community level on initial hospital expenditures, educational attainment and lost earnings as well as to estimate potential savings associated with reductions in preterm birth. STUDY DESIGN: The retrospective, population-based analysis used vital statistics and population demographics from Hamilton County, Ohio, USA, in 2012. METHODS: We adjusted previously reported, mean initial hospital cost estimates (stratified by each week of gestation) to 2012 dollars using national cost-to-charge ratios. Next, we calculated excess costs attributable to prematurity and potential hospital cost savings, which could be realized by prolonging each preterm pregnancy by a single week of gestation. Using reported associations among preterm birth, educational attainment and adult earnings, we developed generalizable formulas to calculate lost academic degrees and lost income estimates attributable to preterm birth. The formulas generated estimates based on local population demographics. RESULTS: The annual initial hospital cost associated with 1444 preterm infants was estimated at $93 million. In addition, over 9000 fewer college degrees and over $300 million in lost annual earnings were attributed to local adults who were born preterm. Prolonging each preterm birth by 1 week could potentially reduce initial hospital expenditures by over $25 million. Additional potential savings could be realized as healthier infants attain higher levels of education and earnings as adults. CONCLUSIONS: The generalizable methods developed for estimating the economic impact of preterm birth at the community level can be used by any community in which vital statistics and population demographics are available. Cost estimates can serve to rally support for local stakeholder investment in developing strategies for preterm birth intervention leading to improved pregnancy outcomes.

Mature T-lineage leukemia with growth factor-induced multilineage differentiation.

We report an acute T-lymphoblastic leukemia with a predominantly mature CD3+ CD7+ WT31+ phenotype that was induced to differentiate into different cell lineages by various recombinant human growth factors. In the presence of IL-3 or GM-CSF, the leukemic cells gave rise to myeloid and monocytic cells including terminally differentiated, partially functional, segmented neutrophilic granulocytes as assessed by morphologic, cytochemical, immunophenotypic, and functional criteria. In the presence of IL-2, leukemic granulated lymphoid cells exhibiting MHC-unrestricted cytotoxicity and expressing a CD2+ CD3+ CD5+ CD7+ CD8+ CD33+ WT31+ Leu19+ phenotype arose. Leukemic cell cultures initiated with IL-3 yielded growth factor-independent cells with a mixed lineage phenotype and morphologic and cytochemical evidence of immature blasts. These were T lymphocyte and myeloid surface antigen (CD2,CD3,CD5,CD7,CD13,CD33,WT31) positive. Identical rearrangements of the constant region of the TCR-delta gene and of the joining regions of the TCR-beta, -gamma, and -delta genes were observed in the fresh and all cultured leukemic cells, indicating that they were derived from the same malignant clone. Consistent with the molecular genetic data, the cytogenetic analyses of the GM-CSF-, IL-3-cultured and the growth factor-independent leukemic cells showed the presence of multiple, closely related abnormal clones, all of which had an interstitial deletion of part of the long arm of chromosome 6 and a complex 1;10;12 translocation. In conclusion, these data demonstrate the involvement of a multipotent leukemic precursor cell in this predominantly mature CD2+ CD3+ CD5+ CD7+ WT31+ T-ALL. This multipotent leukemic precursor may be susceptible to various growth factors and respond with ordered differentiation and maturation.

T cell receptor gamma and delta rearrangements in hematologic malignancies. Relationship to lymphoid differentiation.

We have studied recombinatorial events of the T cell receptor delta and gamma chain genes in hematopoietic malignancies and related these to normal stages of lymphoid differentiation. T cell receptor delta gene recombinatorial events were found in 91% of acute T cell lymphoblastic leukemia, 68% of non-T, non-B lymphoid precursor acute lymphoblastic leukemia (ALL) and 80% of mixed lineage acute leukemias. Mature B-lineage leukemias and acute nonlymphocytic leukemias retained the T-cell receptor delta gene in the germline configuration. The incidence of T cell receptor gamma and delta was particularly high in CD10+CD19+ non-T, non-B lymphoid precursor ALL. In lymphoid precursor ALL, T cell receptor delta was frequently rearranged while T cell receptor gamma was in the germline configuration. This suggests that TCR delta rearrangements may precede TCR gamma rearrangements in lymphoid ontogeny. In T-ALL, only concordant T cell receptor delta and gamma rearrangements were observed. Several distinct rearrangements were defined using a panel of restriction enzymes. Most of the rearrangements observed in T-ALL represented joining events of J delta 1 to upstream regions. In contrast, the majority of rearrangements in lymphoid precursor ALL most likely represented D-D or V-D rearrangements, which have been found to be early recombinatorial events of the TCR delta locus. We next analyzed TCR delta rearrangements in five CD3+TCR gamma/delta+ ALL and cell lines. One T-ALL, which demonstrated a different staining pattern with monoclonal antibodies against the products of the TCR gamma/delta genes than the PEER cell line, rearranges J delta 1 to a currently unidentified variable region.

Structural basis of von Willebrand factor binding to platelet glycoprotein Ib and collagen. Effects of disulfide reduction and limited proteolysis of polymeric von Willebrand factor.

von Willebrand factor (vWF) is a large, multimeric glycoprotein that helps platelets adhere to vascular subendothelium. Although vWF binding to platelet receptors and connective tissue constituents is of fundamental importance in adhesion, there is little information regarding the nature of these vWF binding sites. In this paper, we have compared the structural requirements for vWF binding with platelet glycoprotein Ib (GpIb), heparin, and collagen and have shown that fragments derived from large vWF multimers retain biologic activity. We have shown that a 440,000-D subunit produced by disulfide reduction and alkylation of vWF polymer binds to platelet GpIb. When analyzed by polyacrylamide gel electrophoresis and Sepharose CL6B chromatography, the 440,000-D vWF oligomer is a dimer of the 220,000 subunit of fully reduced native vWF. This vWF dimer competes with 125I-vWF for binding to GpIb with an IC50 of 100 micrograms/ml (227 nM). The GpIb binding domain on vWF was further localized by digestion of native vWF polymers with Staphylococcal V8 protease. A 285,000-D fragment of vWF multimer was separated from heterogeneous 210,000-225,000-D fragments by its ability to bind to heparin. The 285,000-D fragment that bound to heparin Sepharose was composed of two disulfide-linked 175,000- and 115,000-D polypeptides. The heterogeneous fragments contained disulfide-linked 96,000, 66,000, and 53,000-D polypeptides when analyzed on polyacrylamide gel electrophoresis. The 285,000-D fragment competed with 125I-vWF for binding to GpIb with an IC50 of 22 micrograms/ml (77 nM), while the other fragments did not compete for binding. Neither the vWF dimer nor the proteolytic fragments competed with native 125I-vWF polymer for binding to collagen.

Acute leukemia expressing the gamma gene product of the putative second T cell receptor.

Early thymus-derived lymphocytes bearing the T gamma gene product in association with the CD3(T3) complex have recently been described. We report a unique case of human acute lymphoblastic leukemia with a CD2+, CD3+, CD4-, CD5+, CD7+, CD8-, WT31- phenotype. These cells were found to have T gamma gene rearrangement and T gamma transcripts in absence of T alpha or T beta rearrangement or transcripts. Immunoprecipitation studies with anti-CD3 antibodies showed a 43-kD protein associated with T3; this 43-kD protein is also precipitated with antiserum raised against synthetic peptides representing the constant region of the putative T gamma protein.

Evaluation of identifier field agreement in linked neonatal records.

OBJECTIVE: To better address barriers arising from missing and unreliable identifiers in neonatal medical records, we evaluated agreement and discordance among traditional and non-traditional linkage fields within a linked neonatal data set. STUDY DESIGN: The retrospective, descriptive analysis represents infants born from 2013 to 2015. We linked children's hospital neonatal physician billing records to newborn medical records originating from an academic delivery hospital and evaluated rates of agreement, discordance and missingness for a set of 12 identifier field pairs used in the linkage algorithm. RESULTS: We linked 7293 of 7404 physician billing records (98.5%), all of which were deemed valid upon manual review. Linked records contained a mean of 9.1 matching and 1.6 non-matching identifier pairs. Only 4.8% had complete agreement among all 12 identifier pairs. CONCLUSION: Our approach to selection of linkage variables and data formatting preparatory to linkage have generalizability, which may inform future neonatal and perinatal record linkage efforts.

Home visiting for first-time mothers and subsequent pregnancy spacing.

OBJECTIVE: The objective of the study was to determine the association of home visiting with subsequent pregnancy outcomes. STUDY DESIGN: Retrospective study of Ohio mothers delivering their first infant from 2007 to 2009. First, we compared mothers enrolled in home visiting with a matched eligible group. Second, we compared outcomes within home visiting based on program participation (low <25% of recommended home visits, moderate 25 to 75%, high 75 to 100% and very high >100%). Time to subsequent pregnancy within 18 months was evaluated using Cox proportional hazards regression; logistic regression tested the likelihood of subsequent preterm birth. RESULTS: Of 1516 participants, 1460 were matched 1:1 to a comparison mother (n=2920). After multivariable adjustment, enrollment was associated with no difference in pregnancy spacing or subsequent preterm birth. Among those enrolled, moderate vs low participants had reduced risk of repeat pregnancy over 18 months (hazard ratio 0.68, P=0.003). CONCLUSION: Increased pregnancy spacing is observed among women with at least moderate home visiting participation.

Self-reported and laboratory evaluation of late pregnancy nicotine exposure and drugs of abuse.

OBJECTIVE: The objective of this study was to evaluate the prevalence of late pregnancy nicotine exposures, including secondhand smoke exposures, and to evaluate the associated risk of exposure to drugs of abuse. STUDY DESIGN: The study was a retrospective single-center cohort analysis of more than 18 months. We compared self-reported smoking status from vital birth records with mass spectrometry laboratory results of maternal urine using a chi-square test. Logistic regression estimated adjusted odds for detection of drugs of abuse based on nicotine detection. RESULTS: Compared with 8.6% self-reporting cigarette use, mass spectrometry detected high-level nicotine exposures for 16.5% of 708 women (P<0.001) and an additional 7.5% with low-level exposures. We identified an increased likelihood of exposure to drugs of abuse, presented as adjusted odds ratios, (95% confidence interval (CI), for both low-level (5.69, CI: 2.09 to 15.46) and high-level (13.93, CI: 7.06 to 27.49) nicotine exposures. CONCLUSION: Improved measurement tactics are critically needed to capture late pregnancy primary and passive nicotine exposures from all potential sources.

A population study of first and subsequent pregnancy smoking behaviors in Ohio.

OBJECTIVE: The objective of this study is to identify maternal characteristics associated with non-smoking during a subsequent pregnancy after first pregnancy smoking. STUDY DESIGN: We conducted a retrospective population-based analysis of Ohio vital birth records from 2007 to 2013. We used logistic regression to calculate adjusted odds ratios with 95% confidence intervals for detection of characteristics associated with non-smoking during a subsequent pregnancy after first pregnancy smoking. RESULTS: Among 75 190 mothers, 75.6% were non-smokers and 13.7% were smokers during both pregnancies. During their first pregnancy, 49.7% of 15 075 smokers quit. Of them, 50.1% remained non-smokers during their subsequent pregnancy. Women who reduced, but continued smoking during their first pregnancy, were more than five times as likely to smoke during their subsequent pregnancy than women who quit (odds ratio (95% confidence interval): 2.85 (2.43 to 3.35) vs 0.55 (0.45 to 0.67)). CONCLUSION: Interventions targeting complete cessation, rather than reduction in smoking among first-time mothers, may be the most effective at optimizing long-term health benefits.

Determination of the quantitative thallium imaging variables that optimize detection of coronary artery disease.

Although quantification of exercise thallium images has been previously reported, the relative value of different imaging variables for detection of coronary artery disease has not been analyzed in a large group of patients with cardiac catheterization data. Regional initial thallium uptake, redistribution and clearance on thallium study were measured in 325 patients also undergoing cardiac catheterization (281 patients with and 44 patients without coronary artery disease). Normal values were defined in 55 other clinically normal subjects. When five myocardial segments were analyzed in each view, the respective values for sensitivity and specificity were 95 and 50% for initial thallium uptake, 60 and 87% for redistribution and 74 and 66% for clearance. Initial thallium uptake was the most sensitive but least specific (p less than 0.001), whereas redistribution was the least sensitive and most specific (p less than 0.001). Using stepwise logistic regression analysis, the best correlate of coronary artery disease was initial thallium uptake. Addition of redistribution to a mathematical model of the probability of coronary artery disease did not alter sensitivity, but increased specificity from 50 to 70% (p less than 0.001). Once initial uptake and redistribution were considered, myocardial thallium clearance provided no additional improvement in the correlation. Excluding the two basal segments in each view from the analysis increased the specificity from 70 to 80% (p less than 0.001) without affecting sensitivity. Of the 15 patients (5%) with coronary disease not detected using this approach, none had left main disease and 10 (67%) had one vessel disease. A combination of variables derived from quantification of exercise thallium images provides a superior sensitivity and specificity for the detection of coronary artery disease compared with the use of a single variable.

Expression of receptor protein tyrosine kinase tif is regulated during leukemia cell differentiation.

tif is a recently cloned and characterized cDNA predicting a transmembrane protein with a putative tyrosine kinase structure in its cytoplasmic domain. By analysis of the purified tif cytoplasmic domain expressed in Escherichia coli, we have demonstrated that tif is an active protein tyrosine kinase capable of autophosphorylation on tyrosine residues and this phosphorylation is inhibited by a tyrosine-specific inhibitor genistein. Northern blot analyses of various leukemia cell lines have revealed that tif mRNA expression is primarily confined to those bearing erythroid and megakaryocytic phenotypes. Megakaryocytic differentiation of K562 and HEL cells induced by phorbol 12-myristate 13-acetate is accompanied by down-regulation of tif mRNA expression. In addition, treatment of K562 and HEL with hexamethylene bis-acetamide, but not with hemin, decreases the steady-state level of tif mRNA. These combined results suggest that the receptor tyrosine kinase tif is involved in hematopoietic development.

Value and limitations of radionuclide angiography in determining the cause of reduced left ventricular ejection fraction: comparison of idiopathic dilated cardiomyopathy and coronary artery disease.

The radionuclide angiograms of 59 patients with a left ventricular (LV) ejection fraction (EF) less than 0.40, 23 with idiopathic dilated cardiomyopathy (IDC) and 36 with coronary artery disease (CAD) were analyzed to assess the usefulness of radionuclide angiography in distinguishing these conditions. Mean right ventricular EF was lower in the IDC group than in the CAD group, 0.31 vs 0.45 (p less than 0.01). LV wall motion was scored from 3 (normal) to -1 (dyskinesia). The incidence of akinesia was similar in IDC and CAD groups, 70% and 83%, respectively. Dyskinesia was more common in the CAD group (42% vs 17%), but the difference was not statistically significant. Segmental wall motion analysis showed similar patterns of wall motion in both groups, with contraction best preserved in the anterobasal, posterobasal and superolateral segments. Patients in the CAD group had worse apical motion (p less than 0.01) and better wall motion in the anterobasal (p less than 0.05) and superolateral walls (p less than 0.01), compared with patients in the IDC group. To assess symmetry of contraction, a maximum difference score was derived for each patient. Symmetry (a score less than 1) was present in 5 IDC and no CAD patients, whereas asymmetry (a score of 2 or more) was present in 27 CAD and 7 IDC patients (p less than 0.01). Wall motion became more symmetric in both groups when LVEF was less than 0.20. Logistic regression analysis revealed that the maximum difference score was the best predictor of the diagnosis, but only because of better separation at the extremes of maximum difference score values.(ABSTRACT TRUNCATED AT 250 WORDS)

Comets as porous aggregates of interstellar dust.

A comet model is derived based on the interstellar dust chemical composition in dense molecular and diffuse clouds resulting from their subsequent chemical interactions and UV photoprocessing. The collapsing presolar nebula leads to a porous aggregate model for comet nuclei, from which is derived certain physical properties that include thermal conductivity and tensile strength. The porous morphological structure is also shown to imply anomalous (expansion rather than contraction) behavior when subjected to strong shock waves, which is supported by recent shock experiments on (porous) carbonaceous chondrite material.

T-cell acute lymphoblastic leukemia and the associated basic helix-loop-helix gene SCL/tal.

T-cell acute lymphoblastic leukemia (T-ALL) is a relatively uncommon disease, constituting only approximately 15% of newly diagnosed acute lymphoblastic leukemias (ALL) in the United States, or roughly 300 cases per year. Outside of the United States, in countries such as Egypt and India, T-ALL may represent as much as 50% of all ALL's but still remains an overall rare disease. The clinical importance of T-ALL lies in its poor responsiveness to therapy that has proved highly effective with standard B-cell precursor ALL (BCP-ALL). The scientific importance of human T-ALL has resided in its role as a cancer prototype, permitting the identification of novel genes centrally involved in both neoplastic change and normal cellular differentiation. One of these genes, SCL/tal, has received significant attention due to its intimate involvement in T-ALL, as well as in normal hematopoiesis. Although a tremendous amount has been recently discovered about SCL/tal, its exact roles in leukemogenesis and normal hematopoiesis remain obscure.

Molecular Structure of the Rearranged T-Cell Gamma Chain Gene in a Human Leukemia Which Expresses Its Product.

The gamma gene product is a component of the second T-cell receptor. We report a new case of acute lymphoblastic leukemia bearing a CD3+ CD4- CD5+ CD7+ CD8- WT31- immunophenpotype that expresses the gamma peptide. Immunoprecipitation studies using an anti Cγ heteroantisera showed two different bands of 40 and 60 Kd. Southern analysis revealed Cγ1 utilization in the productive rearrangement. The demonstration of Vδ-Jδ1 rearrangement in this leukemia suggests that the 60 Kd band could correspond to the product of the delta gene. The utilization of the Jγ1.3 exon in this leukemia suggests that the T lymphocytes that undergo leukemic transformation are derived from a population different from the circulating γ/δ lymphocytes, that preferentially use the Jγ1.2 (JγP) exon.

Inhibition by anticoagulant drugs of the progressive hypertension and uremia associated with renal infarction in rats.

We confirmed our previously reported findings that subcutaneous administration of heparin (200 U q 12 hr) in rats with experimental partial renal infarction prevents the development of progressive renal failure and hypertension, as well as the glomerular abnormalities which occur in the remaining viable renal tissue. In the present study, heparin, in the dosage used to prevent progressive renal failure, caused a marked and sustained prolongation of the activated partial thromboplastin time and prothrombin time, as well as a transient prolongation of the bleeding time. Administration of coumadin at doses which caused a significant prolongation of the prothrombin time and bleeding time also inhibited the development of progressive hypertension and uremia in rats with experimental partial renal infarction. These findings indicate that inhibition of blood coagulation effectively protects rats with experimentally decreased renal mass from the development of progressive renal failure and hypertension and support the concept that the glomerular thrombosis plays an important role in the pathogenesis of these complications.

Are shy people reluctant to ask for help?

Examined the help-seeking behaviors of shy and not-shy men and women. In Study 1, Ss worked on an impossible task in the presence of a male or female confederate whom they were told had just successfully completed the task. Shy Ss asked for help no less frequently than did not-shy Ss overall, but they did seek help less frequently from opposite-sex confederates than from same-sex confederates. In Study 2, shy and not-shy men and women were required to call a man and a woman and ask them to complete a questionnaire. All respondents agreed to return the questionnaire. However, when shy Ss (compared with not-shy Ss) called opposite-sex respondents, fewer of the questionnaires were actually returned. When making their calls, shy Ss sounded somewhat less warm and confident than did not-shy Ss, and they also spoke less fluently. Fluency, in turn, predicted response rate for the shy subjects calling respondents of the opposite sex.

Homochirality as the signature of life: the SETH Cigar.

A characteristic hallmark of life is its homochirality: all biomolecules are usually of one hand, e.g. on Earth life uses only L-amino acids for protein synthesis and not their D mirror images. It is therefore suggested that a search for extra-terrestrial life can be approached as a Search for Extra-Terrestrial Homochirality (SETH). A novel miniaturized space polarimeter, called the SETH Cigar, is described which could he used to detect optical rotation as the homochiral signature of life on other planets. Moving parts are avoided by replacing the normal rotating polarizer by multiple fixed polarizers at different angles as in the eye of the bee. It is believed that homochirality will be found in the subsurface layers on Mars as a relic of extinct life.

Understanding why heterosexual adults do not practice safer sex: a comparison of two samples.

We assessed why heterosexually active adults did not have "safer sex" with their last sexual partner. Subjects enrolled in HIV education and testing trials at a sexually transmitted disease (STD) clinic and a university student health service (SHS) completed questionnaires about their last sexual partner's risk factors for HIV and whether they had safer sex with this partner. Of the 652 sexually active subjects, 61% reported not having safer sex with their last sexual partner and explained why. Low perceived risk of HIV infection was the most common reason, indicated by 62%, though most knew too little about their partner to ensure the encounter was low risk. Other reasons included condom unavailability (20%), the subject "didn't want to" use a condom (19%), "couldn't stop ourselves" (15%), the partner's influence (14%), and alcohol or drug use (11%). Thirty-one percent of subjects indicated more than one reason for not having safer sex. SHS subjects more often reported that the encounter was low risk for HIV transmission (p = 0.0001), while STD subjects more often reported condom unavailability (p = 0.002) and drug and alcohol use (p = 0.003). We conclude that there are many different factors promoting sexual behavior at risk of infection, combinations of which are important, and that these factors differ between samples. Preventive interventions must focus on the factors most important to the targeted population and may need to consider multiple factors simultaneously.

PIP: 255 subjects enrolled in HIV education and testing trials at a sexually transmitted disease (STD) clinic and 397 at a university student health service (SHS) completed questionnaires about their last sex partner's risk factors for HIV and whether they had safer sex with that individual. Subjects in the STD sample were of mean age 27 years, 72% male, 71% never married, 7% White, 86% Black, had a mean 13 years of schooling, had a median 2 STDs, and a lifetime mean of 12 sex partners. Subjects in the SHS sample were of mean age 23 years, 28% male, 93% never married, 67% White, 8% Black, had a mean 15 years of schooling, had a median zero STDs, and a lifetime mean of 6 sex partners. 61% reported not having safer sex with their last sex partner. 62% cited low perceived risk of HIV infection as the reason for not practicing safer sex; condom unavailability, 20%; simply not wanting to use a condom, 19%; losing control, 15%; partner's influence, 14%; and alcohol or drug use, 11%. 31% of subjects indicated more than one reason for not having safer sex. SHS subjects more often reported that the encounter was low risk for HIV transmission, while STD subjects more often reported condom unavailability and drug and alcohol use.

A clinical approach to exercise tolerance testing in coronary artery disease.

Data from exercise tolerance testing should be incorporated into clinical decision making. A strategy for stratification of individual patients into high, indeterminate, and low-risk categories using Bruce protocol exercise testing is outlined. This approach will help to ensure further evaluation of high-risk individuals without excessive testing of patients having excellent long-term prognoses.