bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors for Uterine Leiomyoma: A Practice-based Case-Control Study. I. African-American Heritage, Reproductive History, Body Size, and Smoking
Authors: Faerstein Eduardo , Szklo Moyses , Rosenshein Neil
Published: July 2002

The authors conducted a case-control study among premenopausal women in the Baltimore, Maryland, area to examine the associations of uterine leiomyoma with ethnicity and hormone-related characteristics. Cases of uterine leiomyoma (n = 318) were surgically or sonographically first confirmed between January 1990 and June 1993. A total of 394 controls were selected from women who were visiting their gynecologist for a routine checkup. Data were collected through telephone interviews and abstraction of medical records; 77.8% of eligible cases and 78.0% of eligible controls were interviewed. Positive adjusted associations were observed between risk of uterine leiomyoma and self-described African-American ethnicity (vs. Whites: odds ratio (OR) = 9.4; 95% confidence interval (CI): 5.7, 15.7), early menarche (<11 years vs. >13 years: OR = 2.4; 95% CI: 1.1, 5.6), and high body mass index (upper quartile vs. lower quartile: OR = 2.3; 95% CI: 1.4, 3.8). Inverse associations were observed with use of oral contraceptives (current use vs. never use: OR = 0.2, 95% CI: 0.1, 0.6) and duration of smoking (≥19 years vs. never: OR = 0.6; 95% CI: 0.4, 1.1). Younger ages at infertility diagnosis and at first and last childbirth were more common among cases; however, analyses of data on tumor location suggested that these associations represent predominantly consequences of uterine leiomyoma. These results suggest that development of uterine leiomyoma is associated with increased exposure to ovarian hormones. Possible reasons for the very elevated risk among African-American women need further investigation.
Risk Factors for Uterine Leiomyoma: A Practice-based Case-Control Study. II. Atherogenic Risk Factors and Potential Sources of Uterine Irritation
Authors: Faerstein Eduardo , Szklo Moyses , Rosenshein Neil B.
Published: July 2002

In this case-control study, the authors analyzed associations of uterine leiomyoma with atherogenic risk factors and potential sources of uterine irritation. The study included 318 case women with uterine leiomyoma that was first confirmed between 1990 and 1993 in the Baltimore, Maryland, area and 394 controls selected from women visiting the same gynecologists' offices for routine reasons. Telephone interviews were conducted with 77.8% of eligible cases and 78.0% of eligible controls. Compared with participants with no hypertension history, increased risks were observed among participants with any history of hypertension (odds ratio (OR) = 1.7; 95% confidence interval (CI): 1.0, 2.8), hypertension requiring medication (OR = 2.1; 95% CI: 1.1, 4.1), hypertension diagnosed at ages less than 35 years (for hypertension requiring medication, OR = 2.7; 95% CI: 1.0, 7.6), and hypertension of 5 or more years' duration (for hypertension requiring medication, OR = 3.1; 95% CI: 1.2, 8.2). Estimates of associations with diabetes history were very imprecise but followed similar patterns. Adjusted associations were observed with pelvic inflammatory disease (three or more episodes vs. none: OR = 3.7; 95% CI: 0.9, 15.9), chlamydial infection (history vs. no history: OR = 3.2; 95% CI: 0.8, 13.7), and use of an intrauterine device when it caused infectious complications (use vs. no use: OR = 5.3; 95% CI: 1.8, 16.3). Risk of uterine leiomyoma was also associated in a graded fashion with frequency of perineal talc use (daily use vs. no use: OR = 2.2; 95% CI: 1.4, 3.1). The authors conclude that nonhormonal factors may influence risk of uterine leiomyoma.
Plasma 1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) Levels and Immune Response
Authors: Vine Marilyn F. , Stein Leonard , Weigle Kristen , Schroeder Jane , Degnan Darrah , Tse Chui-Kit J. , Backer Lorraine
Published: July 2002

For determination of whether plasma 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) pesticide levels (≤1–32 ppb) are associated with immune suppression or DNA damage in lymphocytes, 302 individuals residing in Moore County, North Carolina, in 1994–1996 provided a blood specimen, underwent a skin test, and answered a questionnaire concerning factors affecting plasma organochlorine pesticide levels and the immune system. The blood specimens were analyzed for levels of plasma DDE (a metabolite of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane), numbers and types of blood cells, immunoglobulin levels, mitogen-induced lymphoproliferative activity, and lymphocyte micronuclei. When DDE levels were categorized as 1 or less, more than 1 to 2, more than 2 to 4.3, more than 4.3 to 7.6, and more than 7.6 ppb, individuals with higher plasma DDE levels had lowered mitogen-induced lymphoproliferative activity (concanavalin A, range: 74,218 dropping to 55,880 counts per minute, p = 0.03) and modestly increased total lymphocytes (range: 2.0–2.3 × 103/μl, p = 0.05) and immunoglobulin A levels (range: 210–252 mg/dl, p = 0.04). There were no consistent differences in response to the skin tests by plasma DDE levels. Plasma DDE levels were not associated with a higher frequency of micronuclei. The authors conclude that relatively low levels of plasma DDE are associated with statistically significant changes in immune markers, although the magnitude of the effects are of uncertain clinical importance.
Average Volume of Alcohol Consumption, Patterns of Drinking, and All-Cause Mortality: Results from the US National Alcohol Survey
Authors: Rehm Jürgen , Greenfield Thomas K. , Rogers John D.
Published: July 2002

The objective of this study was to investigate the effects of an average volume of alcohol consumption and drinking patterns on all-cause mortality. The sample (n = 5,072) was drawn from the 1984 National Alcohol Survey, representative of the US population living in households. Follow-up time was until the end of 1995, with 532 people deceased during this period. The authors found a significant influence of drinking alcohol on mortality with a J-shaped association for males and an insignificant relation of the same shape for females. When the largest categories of equivalent average volume of consumption were divided into people with and without heavy drinking occasions, serving as an indicator of drinking pattern, this differentiation proved important in predicting mortality. Light to moderate drinkers had higher mortality risks when they reported heavy drinking occasions (defined by either eight drinks per occasion or getting drunk at least monthly). Similarly, when the category of exdrinkers was divided into people who did or did not report heavy drinking occasions in the past, people with heavy drinking occasions had a higher mortality risk. Finally, indicating alcohol problems in the past was related to higher mortality risk. Results emphasized the importance of routinely including measures of drinking patterns into future epidemiologic studies on alcohol-related mortality.
Low Dehydroepiandrosterone and Ischemic Heart Disease in Middle-aged Men: Prospective Results from the Massachusetts Male Aging Study
Authors: Feldman Henry A. , Johannes Catherine B. , Araujo Andre B. , Mohr Beth A. , Longcope Christopher , McKinlay John B.
Published: July 2002

The adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) have been characterized as “protective” against ischemic heart disease (IHD), especially in men, on the basis of sparse epidemiologic evidence. The authors used data from the Massachusetts Male Aging Study, a random sample prospective study of 1,709 men aged 40–70 years at baseline, to test whether serum levels of DHEA or DHEAS could predict incident IHD over a 9-year interval. At baseline (1987–1989) and follow-up (1995–1997), an interviewer-phlebotomist visited each subject in his home to obtain comprehensive health information, body measurements, and blood samples for hormone and lipid analysis. Incident IHD between baseline and follow-up was ascertained from hospital records and death registries, supplemented by self-report and evidence of medication. In the analysis sample of 1,167 men, those with serum DHEAS in the lowest quartile at baseline (<1.6 μg/ml) were significantly more likely to incur IHD by follow-up (adjusted odds ratio = 1.60, 95 percent confidence interval: 1.07, 2.39; p = 0.02), independently of a comprehensive set of known risk factors including age, obesity, diabetes, hypertension, smoking, serum lipids, alcohol intake, and physical activity. Low serum DHEA was similarly predictive. These results confirm prior evidence that low DHEA and DHEAS can predict IHD in men.
Implausible Birth Weight for Gestational Age
Authors: Joseph K. S. , Kramer Michael S. , Allen Alexander C. , Mery Leslie S. , Platt Robert W. , Wu Wen Shi
Published: July 2002

Various rules have been proposed to identify and exclude live births with implausible values of birth weight for gestational age from large perinatal data sets. The authors carried out a preliminary evaluation of common rules by examining the frequency and nature of rule-based exclusions among live births in Canada (excluding Ontario) between 1992 and 1994. There were 625 (0.09%), 133 (0.02%), 170 (0.02%), and 2,858 (0.40%) live births identified for exclusion by a median birth weight for gestational age ±4 standard deviations (SD) rule, a ±5 SD rule, a rule based on expert clinical opinion, and a modification of Tukey's rule, respectively. The birth weight and gestational age distribution of the exclusions depended on the particular rule used; for example, 12.1% and 0.3% of live births of ≥4,500 g were excluded under Tukey's rule and the rule based on expert opinion, respectively. Infant mortality rates among those excluded were 8–13 times higher than among all live births. Current rules for identifying implausible birth weight for gestational age tend to flag live births at high risk for infant death. Such rules may erroneously attenuate temporal trends in important perinatal outcomes.
Is the Risk of Developing Alzheimer's Disease Greater for Women than for Men?
Authors: Hebert Liesi E. , Scherr Paul A. , McCann Judith J. , Beckett Laurel A. , Evans Denis A.
Published: July 2002

A large proportion of people with Alzheimer's disease (AD) are women; however, it is not clear whether this is due to higher risk of disease or solely to the larger number of women alive at ages when AD is common. Beginning in 1982, two stratified random samples of people aged ≥65 years in East Boston, Massachusetts underwent detailed, structured clinical evaluation for prevalent (467 people) and incident (642 people from a cohort previously ascertained to be disease-free) probable AD. The prevalence sample was followed for mortality for up to 11 years (through December 1992). The age-specific incidence of AD did not differ significantly by sex (for men vs. women, odds ratio = 0.92; 95% confidence interval (CI): 0.51, 1.67). Controlled for age, prevalence also did not differ significantly by sex (for men vs. women, odds ratio = 1.29; 95% CI: 0.67, 2.48). The increase in risk of mortality due to AD did not vary by sex. The odds ratio for women with AD compared with women without AD was 2.07 (95% CI: 1.21, 3.56). For men, the odds ratio was 2.22 (95% CI: 1.02, 4.81). These findings suggest that the excess number of women with AD is due to the longer life expectancy of women rather than sex-specific risk factors for the disease.
Factors Associated with Earthquake Deaths in the Great Hanshin-Awaji Earthquake, 1995
Authors: Osaki Yoneatsu , Minowa Masumi
Published: July 2002

The authors conducted descriptive and case-control studies to find factors associated with earthquake deaths due to the Great Hanshin-Awaji earthquake on January 17, 1995, in Nishinomiya, Japan. In the case-control study, cases included all 1,104 deaths. Controls were randomly selected from survivors. Earthquake mortality increased for people over age 50 years. Mortality among people who had lived in dwellings that were completely destroyed was much higher. One risk factor was physical disabilities (odds ratio = 1.9, 95% confidence interval (CI): 1.0, 3.4). When the analysis was limited to the people who had lived in intact or partially destroyed dwellings, the odds ratio rose to 5.6 (95% CI: 1.6, 19.8).
Seasonal Variation in Household, Occupational, and Leisure Time Physical Activity: Longitudinal Analyses from the Seasonal Variation of Blood Cholesterol Study
Authors: Matthews Charles E. , Freedson Patty S. , Hebert James R. , Stanek Edward J. , Merriam Philip A. , Rosal Milagros C. , Ebbeling Cara B. , Ockene Ira S.
Published: July 2002

The authors examined seasonal variation in physical activity in longitudinal analyses of 580 healthy adults from Worcester, Massachusetts (the Seasonal Variation of Blood Cholesterol Study, 1994–1998). Three 24-hour physical activity recalls administered five times during 12 months of follow-up were used to estimate household, occupational, leisure time, and total physical activity levels in metabolic equivalent (MET)-hours/day. Trigonometric models were used to estimate the peak-to-trough amplitude and phase of the peaks in activity during the year. Total activity increased by 1.4 MET-hours/day (121 kcal/day) in men and 1.0 MET-hours/day (70 kcal/day) in women during the summer in comparison with winter. Moderate intensity nonoccupational activity increased by 2.0–2.4 MET-hours/day in the summer. During the summer, objectively measured mean physical activity increased by 51 minutes/day (95% confidence interval: 20, 82) in men and by 16 minutes/day (95% confidence interval: −12, 45) in women. The authors observed complex patterns of seasonal change that varied in amplitude and phase by type and intensity of activity and by subject characteristics (i.e., age, obesity, and exercise). These findings have important implications for clinical research studies examining the health effects of physical activity and for health promotion efforts designed to increase population levels of physical activity.
Apolipoprotein E Genotypes and the Incidence of Alzheimer's Disease among Persons Aged 75 Years and Older: Variation by Use of Antihypertensive Medication?
Authors: Guo Zhenchao , Fratiglioni Laura , Viitanen Matti , Lannfelt Lars , Basun Hans , Fastbom Johan , Winblad Bengt
Published: July 2002

The authors examined the impact of the apolipoprotein E (APOE)*ε4 allele on Alzheimer's disease incidence in relation to use of antihypertensive medication. A population-based (Kungsholmen Project) cohort of 985 nondemented Swedish subjects aged ≥75 years was followed for an average of 3 years (1990–1992); 164 dementia (122 Alzheimer's disease) cases were identified. Compared with *ε3/*ε3, the APOE  *ε4 allele increased the risk of developing dementia (relative risk (RR) = 1.5, 95% confidence interval (CI): 1.1, 2.1) and Alzheimer's disease (RR = 1.7, 95% CI: 1.2, 2.5). Subjects using antihypertensive medication at baseline (n = 432, 80% used diuretics) had a decreased risk of dementia (RR = 0.6, 95% CI: 0.5, 0.9) and Alzheimer's disease (RR = 0.5, 95% CI: 0.3, 0.8) after adjustment for several variables, including APOE. The effect of antihypertensive medication use was more pronounced among *ε4 carriers. For those not using antihypertensive medication, the relative risks of dementia and Alzheimer's disease for carriers were 2.2 (95% CI: 1.4, 3.4) and 2.3 (95% CI: 1.4, 3.7), respectively. The corresponding relative risks for those using antihypertensive medication were 0.9 (95% CI: 0.5, 1.6) and 1.1 (95% CI: 0.6, 2.2). The APOE  *ε4 allele is an important predictor of dementia and Alzheimer's disease incidence. Further studies are needed to clarify whether use of antihypertensive medication, especially diuretics, modifies the effect of the allele.
Placental Abruption and Perinatal Mortality in the United States
Authors: Ananth Cande V. , Wilcox Allen J.
Published: July 2002

Placental abruption is an uncommon obstetric complication associated with high perinatal mortality rates. The authors explored the associations of abruption with fetal growth restriction, preterm delivery, and perinatal survival. The study was based on 7,508,655 singleton births delivered in 1995 and 1996 in the United States. Abruption was recorded in 6.5 per 1,000 births. Perinatal mortality was 119 per 1,000 births with abruption compared with 8.2 per 1,000 among all other births. The high mortality with abruption was due, in part, to its strong association with preterm delivery; 55% of the excess perinatal deaths with abruption were due to early delivery. Furthermore, babies in the lowest centile of weight (<1% adjusted for gestational age) were almost nine times as likely to be born with abruption than those in the heaviest (≥90%) birth weight centiles. This relative risk progressively declined with higher birth weight centiles. After controlling for fetal growth restriction and early delivery, the high risk of perinatal death associated with abruption persisted. Even babies born at 40 weeks of gestation and birth weight of 3,500–3,999 g (where mortality was lowest) had a 25-fold higher mortality with abruption. The link between fetal growth restriction and abruption suggests that the origins of abruption lie at least in midpregnancy and perhaps even earlier.
Empirical Evidence of Correlated Biases in Dietary Assessment Instruments and Its Implications
Authors: Kipnis Victor , Midthune Douglas , Freedman Laurence S. , Bingham Sheila , Schatzkin Arthur , Subar Amy , Carroll Raymond J.
Published: July 2002

Multiple-day food records or 24-hour recalls are currently used as “reference” instruments to calibrate food frequency questionnaires (FFQs) and to adjust findings from nutritional epidemiologic studies for measurement error. The common adjustment is based on the critical requirements that errors in the reference instrument be independent of those in the FFQ and of true intake. When data on urinary nitrogen level, a valid reference biomarker for nitrogen intake, are used, evidence suggests that a dietary report reference instrument does not meet these requirements. In this paper, the authors introduce a new model that includes, for both the FFQ and the dietary report reference instrument, group-specific biases related to true intake and correlated person-specific biases. Data were obtained from a dietary assessment validation study carried out among 160 women at the Dunn Clinical Nutrition Center, Cambridge, United Kingdom, in 1988–1990. Using the biomarker measurements and dietary report measurements from this study, the authors compare the new model with alternative measurement error models proposed in the literature and demonstrate that it provides the best fit to the data. The new model suggests that, for these data, measurement error in the FFQ could lead to a 51% greater attenuation of true nutrient effect and the need for a 2.3 times larger study than would be estimated by the standard approach. The implications of the results for the ability of FFQ-based epidemiologic studies to detect important diet-disease associations are discussed. Am J Epidemiol 2001;153:394–403.
Plasma Folate, Vitamin B12, and Homocyst(e)ine Concentrations in Preeclamptic and Normotensive Peruvian Women
Authors: Sanchez Sixto E. , Zhang Cuilin , Rene Malinow M. , Ware-Jauregui Suzie , Larrabure Gloria , Williams Michelle A.
Published: July 2002

The authors measured maternal third trimester plasma folate, vitamin B12, and homocyst(e)ine concentrations among 125 women with preeclampsia and 179 normotensive women in Lima, Peru (1997–1998), to determine whether these analytes were associated with the occurrence of preeclampsia. Logistic regression procedures were used to calculate maximum likelihood estimates of odds ratios and 95% confidence intervals. Relative to women in the upper quartile of the control distribution of maternal plasma folate concentrations, women with values in the lowest quartile experienced a 1.6-fold increased risk of preeclampsia (odds ratio = 1.6; 95% confidence interval: 0.8, 3.2). There was no evidence of an increased risk of preeclampsia associated with low plasma vitamin B12 concentrations. The unadjusted relative risk of preeclampsia increased across successively higher quartiles of plasma homocyst(e)ine level (odds ratios were 1.0, 1.0, 1.5, and 2.9, respectively, with the lowest quartile used as the referent; p for linear trend = 0.0004). After adjustment for maternal age, parity, gestational age, use of prenatal vitamins, whether the pregnancy had been planned, and educational attainment, the relative risk between extreme quartiles was 4.0 (95% confidence interval: 1.8, 8.9). These findings are consistent with earlier reports suggesting that hyperhomocyst(e)inemia in pregnancy may be a risk factor for preeclampsia.
Association of Transposition of the Great Arteries in Infants with Maternal Exposures to Herbicides and Rodenticides
Authors: Loffredo Christopher A. , Silbergeld Ellen K. , Ferencz Charlotte , Zhang Jianyi
Published: July 2002

The Baltimore-Washington Infant Study, a case-control study of congenital heart defects in liveborn infants conducted in 1981–1989, interviewed parents about a wide range of environmental exposures that occurred during and before the pregnancy. In the period 1987–1989, the questionnaire was expanded to include a detailed inquiry about exposures to pesticides. An analysis of these latter data revealed an association of maternal exposure to any pesticides during the first trimester with transposition of the great arteries in their infants (TGA; n = 66 infants), relative to 771 control infants, with an odds ratio of 2.0 (95% confidence interval (CI): 1.2, 3.3). No other heart defects were associated with pesticides. When analyzed by type of pesticide and adjusted for covariates, there were associations of TGA with maternal exposures to herbicides (odds ratio (OR) = 2.8; 95% CI: 1.3, 7.2) and to rodenticidal chemicals (OR = 4.7; 95% CI: 1.4, 12.1) but not to insecticides (OR = 1.5; 95% CI: 0.9, 2.6). No data were collected on specific chemicals or brand names. These results raise new questions about the possible epidemiologic association of TGA with some classes of pesticides and warrant new, carefully targeted investigations.
Skin Cancer Risk in Relation to Toenail Arsenic Concentrations in a US Population-based Case-Control Study
Authors: Karagas Margaret R. , Stukel Therese A. , Morris J. Steven , Tosteson Tor D. , Weiss Julia E. , Spencer Steven K. , Greenberg E. Robert
Published: July 2002

Arsenic is a known carcinogen specifically linked to skin cancer occurrence in regions with highly contaminated drinking water or in individuals who took arsenic-containing medicines. Presently, it is unknown whether such effects occur at environmental levels found in the United States. To address this question, the authors used data collected on 587 basal cell and 284 squamous cell skin cancer cases and 524 controls interviewed as part of a case-control study conducted in New Hampshire between 1993 and 1996. Arsenic was determined in toenail clippings using instrumental neutron activation analysis. The odds ratios for squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) were close to unity in all but the highest category. Among individuals with toenail arsenic concentrations above the 97th percentile, the adjusted odds ratios were 2.07 (95% confidence interval (CI): 0.92, 4.66) for SCC and 1.44 (95% CI: 0.74, 2.81) for BCC, compared with those with concentrations at or below the median. While the risks of SCC and BCC did not appear elevated at the toenail arsenic concentrations detected in most study subjects, the authors cannot exclude the possibility of a dose-related increase at the highest levels of exposure experienced in the New Hampshire population.
Association of Perforation of the Appendix with Female Tubal Infertility
Authors: Urbach David R. , Marrett Loraine D. , Kung Rose , Cohen Marsha M.
Published: July 2002

Although perforation of the appendix is considered a risk factor for female tubal infertility, the epidemiologic evidence supporting this relation is inconsistent. Risk factors for tubal infertility were compared for 121 women with documented primary tubal infertility attending in vitro fertilization clinics in Toronto, Canada, from July to December 1998 and 490 controls who were pregnant during the same time period. Self-administered questionnaires and review of medical records were used to assess exposures. The authors found that neither history of acute appendicitis nor perforation of the appendix was a statistically significant risk factor for tubal infertility. The crude odds ratio for perforated appendicitis was 3.4 (95% confidence interval (CI): 0.9, 12.9), and the adjusted odds ratio was 1.4 (95% CI: 0.3, 6.2). In addition to increased age and annual income, cigarette smoking (odds ratio (OR) = 2.0, 95% CI: 1.2, 3.2), history of endometriosis (OR = 6.0, 95% CI: 2.8,12.8), and history of pelvic inflammatory disease (OR = 6.0, 95% CI: 2.8, 12.8) were significantly associated with tubal infertility in multivariate analysis. These data do not provide substantial evidence that perforation of the appendix is an important risk factor for female tubal infertility.
Human and Pet-related Risk Factors for Household Evacuation Failure During a Natural Disaster
Authors: Heath Sebastian E. , Kass Philip H. , Beck Alan M. , Glickman Larry T.
Published: July 2002

This study characterized risk factors for household evacuation failure. A random digit dial telephone survey was conducted of 397 households in Yuba County, California, in July 1997, 6 months after residents had been under evacuation notice due to flooding. Case households failed to evacuate, whereas control households evacuated. The cumulative incidence of household evacuation failure was 19.4%. Fewer households with children (25.8%) failed to evacuate than households without children (45.9%, p < 0.01). More households with pets (20.9%) than households without pets failed to evacuate (16.3%, p = 0.11). With multivariate logistic regression, the risk of household evacuation failure was lower in households with children (odds ratio = 0.4, 95% confidence interval: 0.2, 0.8) compared with households without children. The risk of household evacuation failure increased in pet-owning households without children (odds ratio = 1.3, 95% confidence interval: 1.1, 1.5) compared with pet-owning households with children; the more pets a household owned, the higher the risk of household evacuation failure was. Impediments to pet evacuation, including owning multiple pets, owning outdoor dogs, or not having a cat carrier, explained why many households that owned pets failed to evacuate. Predisaster planning should place a high priority on facilitating pet evacuation through predisaster education of pet owners and emergency management personnel.
Association of the B-Vitamins Pyridoxal 5′-Phosphate (B6), B12, and Folate with Lung Cancer Risk in Older Men
Authors: Hartman Terryl J. , Woodson Karen , Stolzenberg-Solomon Rachael , Virtamo Jarmo , Selhub Jacob , Barrett Michael J. , Albanes Demetrius
Published: July 2002

A nested case-control study was conducted within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort to test for associations between selected B-vitamins (folate, vitamin B6, vitamin B12) and incident lung cancer. This trial was conducted in Finland between 1985 and 1993. Serum was analyzed for these nutrients and homocysteine among 300 lung cancer cases and matched controls (1:1). Odds ratios and 95% confidence intervals were determined in conditional and unconditional (controlling for the matching factors) logistic regression models, after adjusting for body mass index, years of smoking, and number of cigarettes smoked per day. No significant associations were seen between serum folate, vitamin B12, or homocysteine and lung cancer risk. The authors found significantly lower risk of lung cancer among men who had higher serum vitamin B6 levels. Compared with men with the lowest vitamin B6 concentration, men in the fifth quintile had about one half of the risk of lung cancer (odds ratio = 0.51; 95% confidence interval: 0.23, 0.93; p-trend = 0.02). Adjusting for any of the other serum factors (folate, B12, and homocysteine) either alone or jointly did not significantly alter these estimates. This is the first report from a prospectively conducted study to suggest a role for vitamin B6 in lung cancer.
BLAST PRINTS--alternative perspectives on sequence similarity.
Authors: Wright W , Scordis P , Attwood T K
Published: July 2002

SUMMARY: An implementation of BLAST for searching the PRINTS database is presented. The interface allows submission of either protein or DNA queries, and returns the familiar form of output, but modified by means of direct links both to the familial discriminators in PRINTS and to fingerprint profile visualization software. The server thus couples the rapidity of BLAST searching with the sensitivity of fingerprint diagnoses, providing alternative perspectives on a given query. AVAILABILITY: http://www.biochem.ucl. ac.uk/cgi-bin/wright/printsBLAST.cgi
Inferring qualitative relations in genetic networks and

metabolic pathways
Authors: Akutsu Tatsuya , Miyano Satoru , Kuhara Satoru
Published: July 2002

Motivation: Inferring genetic network architecture from time series data of gene expression patterns is an important topic in bioinformatics. Although inference algorithms based on the Boolean network were proposed, the Boolean network was not sufficient as a model of a genetic network.

Results: First, a Boolean network model with noise is proposed, together with an inference algorithm for it. Next, a qualitative network model is proposed, in which regulation rules are represented as qualitative rules and embedded in the network structure. Algorithms are also presented for inferring qualitative relations from time series data. Then, an algorithm for inferring S-systems (synergistic and saturable systems) from time series data is presented, where S-systems are based on a particular kind of nonlinear differential equation and have been applied to the analysis of various biological systems. Theoretical results are shown for Boolean networks with noises and simple qualitative networks. Computational results are shown for Boolean networks with noises and S-systems, where real data are not used because the proposed models are still conceptual and the quantity and quality of currently available data are not enough for the application of the proposed methods.

Contact: takutsu@ims.u-tokyo.ac.jp

To whom correspondence should be addressed.
A clustered spatial-temporal model of rainfall
Authors: Northrop Paul
Published: July 2002

A spatial–temporal model of rainfall is studied in which storms arrive in a Poisson process in time, each storm giving rise to a random number of elliptical rain cells. Each rain cell moves with a random velocity for a random time before terminating. Rain is deposited by the cell at a random intensity which is constant over the area of the cell and over its lifetime. The main properties of this model are studied analytically where possible. Further properties and the aggregation of model properties over space for direct comparison with rainfall radar data require the numerical evaluation of integrals.
Why do cytotoxic T lymphocytes fail to eliminate hepatitis C virus? Lessons from studies using major histocompatibility complex class I peptide tetramers
Authors: Lechner Franziska , Sullivan John , Spiegel Hans , Nixon Douglas F. , Ferrari Belinda , Davis Andrew , Borkowsky Bill , Pollack Henry , Barnes Ellie , Dusheiko Geoff , Klenerman Paul
Published: July 2002

Hepatitis C virus (HCV) infection is a major public health problem, affecting an estimated 3% of the world's population, and over 10% in some countries. Infection in most cases becomes persistent, and can lead to hepatic inflammation, fibrosis and liver failure. The T lymphocyte reponse, in particular that mediated by cytotoxic T lymphocytes (CTLs), is likely to be involved in determining the outcome of infection, although its overall role is not clear. The use of major histocompatibility complex (MHC) class I peptide tetrameric complexes (tetramers) to study antiviral CTL responses has revolutionized our approach to the study of human infection. We have used a panel of MHC class I tetramers to analyse immune responses in HCV–infected individuals at various stages of disease. We find that the CTL response against HCV is vigorous in its early phases but dwindles over time both in terms of lymphocyte number and function. A number of potential explanations for this ‘CTL failure’ are discussed.
Oligomerization and ligand binding in a homotetrameric hemoglobin: Two high‐resolution crystal structures of hemoglobin Bart's (γ4), a marker for α‐thalassemia
Authors: Kidd Richard D. , Baker Heather M. , Mathews Antony J. , Brittain Thomas , Baker Edward N.
Published: July 2002

Hemoglobin (Hb) Bart's is present in the red blood cells of millions of people worldwide who suffer from α‐thalassemia. α‐Thalassemia is a disease in which there is a deletion of one or more of the four α‐chain genes, and excess γ and β chains spontaneously form homotetramers. The γ4 homotetrameric protein known as Hb Bart's is a stable species that exhibits neither a Bohr effect nor heme–heme cooperativity. Although Hb Bart's has a higher O2 affinity than either adult (α2β2) or fetal (α2γ2) Hbs, it has a lower affinity for O2 than HbH (β4). To better understand the association and ligand binding properties of the γ4 tetramer, we have solved the structure of Hb Bart's in two different oxidation and ligation states. The crystal structure of ferrous carbonmonoxy (CO) Hb Bart's was determined by molecular replacement and refined at 1.7 Å resolution (R = 21.1%, Rfree = 24.4%), and that of ferric azide (N3−) Hb Bart's was similarly determined at 1.86 Å resolution (R = 18.4%, Rfree = 22.0%). In the carbonmonoxy–Hb structure, the CO ligand is bound at an angle of 140°, and with an unusually long Fe‐C bond of 2.25 Å. This geometry is attributed to repulsion from the distal His63 at the low pH of crystallization (4.5). In contrast, azide is bound to the oxidized heme iron in the methemoglobin crystals at an angle of 112°, in a perfect orientation to accept a hydrogen bond from His63. Compared to the three known quaternary structures of human Hb (T, R, and R2), both structures most closely resemble the R state. Comparisons with the structures of adult Hb and HbH explain the association and dissociation behaviour of Hb homotetramers relative to the heterotetrameric Hbs.
Rational design of enantioselective enzymes requires considerations of entropy
Authors: Ottosson Jenny , Rotticci‐Mulder Johanna C. , Rotticci Didier , Hult Karl
Published: July 2002

Entropy was shown to play an equally important role as enthalpy for how enantioselectivity changes when redesigning an enzyme. By studying the temperature dependence of the enantiomeric ratio E of an enantioselective enzyme, its differential activation enthalpy (ΔR‐SΔH‡) and entropy (ΔR‐SΔS‡) components can be determined. This was done for the resolution of 3‐methyl‐2‐butanol catalyzed by Candida antarctica lipase B and five variants with one or two point mutations. ΔR‐SΔS‡ was in all cases equally significant as ΔR‐SΔH‡ to E. One variant, T103G, displayed an increase in E, the others a decrease. The altered enantioselectivities of the variants were all related to simultaneous changes in ΔR‐SΔH‡ and ΔR‐SΔS‡. Although the changes in ΔR‐SΔH‡ and ΔR‐SΔS‡ were of a compensatory nature the compensation was not perfect, thereby allowing modifications of E. Both the W104H and the T103G variants displayed larger ΔR‐SΔH‡ than wild type but exhibited a decrease or increase, respectively, in E due to their different relative increase in ΔR‐SΔS‡.
Haspin‐like proteins: A new family of evolutionarily conserved putative eukaryotic protein kinases
Authors: Higgins Jonathan M.G.
Published: July 2002

Haspin (haploid germ cell–specific nuclear protein kinase) is reported to be a serine/threonine kinase that may play a role in cell‐cycle cessation and differentiation of haploid germ cells. In addition, Haspin mRNA can be detected in diploid cell lines and tissues. Here, Haspin‐like proteins are identified in several major eukaryotic phyla—including yeasts, plants, flies, fish, and mammals—and an extended group in Caenorhabditis elegans. The Haspin‐like proteins have a complete but divergent eukaryotic protein kinase domain sequence. Although clearly related to one another and to other eukaryotic protein kinases, the Haspin‐related proteins lack conservation of a subset of residues that are almost invariant in known kinases and possess distinctive inserted regions. In fact, phylogenetic analysis indicates that the Haspin‐like proteins form a novel eukaryotic protein kinase family distinct from those previously defined. The identification of related proteins in model organisms provides some initial insight into their functional properties and will provide new experimental avenues by which to determine the function of the Haspin proteins in mammalian cells.
Automated seed detection and three‐dimensional reconstruction. II. Reconstruction of permanent prostate implants using simulated annealing
Authors: Tubic Dragan , Zaccarin André , Beaulieu Luc , Pouliot Jean
Published: July 2002

We present an algorithm, based on simulated annealing, for automatic seed matching and three‐dimensional spatial coordinate reconstruction using either three radiographic films or three fluoroscopic images taken from different perspectives. The matching problem is defined in the framework of combinatorial optimization, which allows robust reconstruction in presence of calibration imprecision, patient movements, and isometric distortions. Furthermore, by using a global criterion to select the correct matching, we evade common problems of the three‐film method and its variants in presence of noise. The algorithm has been tested on 112 clinical cases and 100 simulated implants and used clinically on more than 100 cases. Simulated implants were reconstructed with an average error of 0.21 mm. For clinical cases, comparison of the precision is performed between results obtained with this new method and results obtained using the three‐film technique. Compared to the latter technique, the reconstruction precision was improved in 62% of the clinical cases.
Verification of radiosurgery target point alignment with an electronic portal imaging device (EPID)
Authors: Dong Lei , Shiu Almon , Tung Samuel , Boyer Arthur
Published: July 2002

A procedure has been developed using an electronic portal imaging device (EPID) to verify that the center of a patient's lesion is aligned with the center of a treatment cone prior to treatment in a linac‐based stereotactic radiosurgery procedure. The coordinates of the lesion center are set on the Brown–Roberts–Wells phantom base using a target simulator. A 3 mm tungsten ball, mounted on the target simulator, is used as the reference point for the planned isocenter. The target simulator is then attached to an adapter mounted on the linac couch, and an EPID image of the simulated target is acquired. The center of the circular‐shaped radiation field is calculated from the centroid of the segmented EPID image, and the center of the tungsten ball is identified by an automated computer search algorithm. A summation filter is used to find the position of the lowest radiation intensity coincident with the center of the ball. The alignment error is defined as the difference between the center of the radiation field and the center of the ball. The accuracy of this method was tested and found to be within 0.2 mm. The advantage of the EPID‐based procedure is that it can give quantitative offset values quickly for immediate readjustment. We have found that the method is also a convenient tool for testing room laser alignment and the accuracy of the treatment cones.
Calculation of enhanced dynamic wedge factors for symmetric and asymmetric photon fields
Authors: Gibbons John P.
Published: July 2002

A method is introduced to calculate wedge factors for an enhanced dynamic wedge (EDW). An analytic formula has been derived that allows the determination of wedge factors at the center of symmetric and asymmetric photon fields. The formalism is an extension of the “MU fraction approximation,” which holds that the dynamic wedge factor is equal to the fraction of MU delivered to the point of calculation. Extensive data are presented, comparing measured enhanced dynamic wedge factors with the current method and the MU fraction model for both symmetric and asymmetric fields. For both 6 and 18 MV photons, the current method demonstrates improved results: Agreement to within 1% is obtained in all symmetric fields and within 2% for all asymmetric fields compared with discrepancies of up to 4% obtained with the MU fraction model.
Area x‐ray beam equalization for digital angiography
Authors: Molloi Sabee , Tang Jerry , Mather Tarun , Zhou Yifang
Published: July 2002

An area beam equalization technique has been investigated in order to generate patient‐specific compensating filters for digital angiography. An initial image was used to generate the compensating filter, which was fabricated using a deformable compensating material, containing and an array of square pistons. The attenuator thicknesses were calculated using the gray level information from the initial unequalized image. The array of pistons was pressed against a uniform thickness of attenuating material to generate a filter for x‐ray beam equalization. The filter was subsequently inserted into the x‐ray beam for the final equalized radiograph. It was positioned close to the focal spot (magnification of 8.0) in order to minimize edge artifacts from the filter. The equalization of x‐ray transmission across the field exiting from the object significantly improved the image quality by preserving local contrast throughout the image. The contrast‐to‐noise ratio (CNR) in the equalized images was increased by up to fivefold. Phantom studies indicate that equalized images using a relatively small array of pistons (e.g., produce significant improvement in image quality with negligible perceptible artifacts. Animal studies showed that beam equalization significantly improved fluoroscopic and angiographic image quality. X‐ray beam equalization produced an image with a relatively uniform scatter‐glare intensity and it reduced the scatter‐glare fraction in the previously underpenetrated region of the image from 0.65 to 0.50. Also, x‐ray tube loading due to the mask assembly itself was negligible. In conclusion, area beam equalization reduces the scatter‐glare fraction and significantly improves CNR in the previously underpenetrated region of the image.
Methods to determine the fluorescence and Auger spectra due to decay of radionuclides or due to a single atomic‐subshell ionization and comparisons with experiments
Authors: Stepanek Jiri
Published: July 2002

The aim of this work is to describe methods of determining the fluorescence and Auger spectra due to decay of radionuclides or a single atomic‐subshell ionization. First discussed is the electron vacancy generation in an atomic subshell by ionization, internal‐conversion decay, or electron‐capture decay. Later discussed is the status of electron vacancy following emission of fluorescence x rays and Auger electrons. Special attention is given to the relaxation probabilities and the procedures to calculate energies of released electrons. Also discussed are the Monte Carlo and deterministic methods to calculate vacancy cascades.
A simple extension of Rüchardt’s method for measuring the ratio of specific heats of air using microcomputer-based laboratory sensors
Authors: Severn G. D. , Steffensen T.
Published: July 2002

A lower division laboratory experiment is described which measures the ratio of specific heats for air, γ≡Cp/Cv, using Rüchardt’s method augmented by microcomputer-based laboratory sensors. A low pressure gauge transducer records the damped pressure oscillations, leading to a value of γ=1.41±0.04. Adding a laser switch, one can extend the method to determine γ from the ratio of pressure and volume variations, γ=−(dp/dV)(V/p), which yields 1.33±0.05. Nonadiabatic processes are considered.
Using Feynman diagrams to solve the classical harmonic oscillator
Authors: Thorndike Alan
Published: July 2002

The method of Feynman diagrams is used to solve the classical oscillator and a coupled oscillator problem.
Atomic spectroscopy with violet laser diodes
Authors: Gustafsson U. , Alnis J. , Svanberg S.
Published: July 2002

Laser spectroscopy with laser diodes can now also be performed in the violet/blue spectral region. A 5 mW commercially available CW laser diode operating at 404 nm was used to perform spectroscopy on potassium atoms with signal detection in absorption as well as fluorescence when operating on a potassium vapor cell and with optogalvanic detection on a potassium hollow cathode lamp. The 4s 2S1/2–5p 2P3/2,1/2 transitions were observed at 404.5 and 404.8 nm, respectively. The laser diode was operated with a standard laser diode driver, and with or without an external cavity. The 4s 2S1/2–4p 2P1/2 transition at 770.1 nm was also observed with a different laser diode. Here, Doppler-free saturated-absorption signals were also observed, enabling the evaluation of the ground-state hyperfine splitting of about 460 MHz. The data recorded allows an experimental verification of the theory for Doppler broadening at two widely separated wavelengths.
Nonlinear phenomena in the natural howling of a dog–wolf mix
Authors: Riede Tobias , Herzel Hanspeter , Mehwald Doreen , Seidner Wolfram , Trumler Erika , Böhme Gerhard , Tembrock Günter
Published: July 2002

It was reported to the first author that a female dog–wolf mix showed anomalously rough-sounding vocalization. Spectral analysis of recordings of the vocalization revealed frequency occurrences of subharmonics, biphonation (two independent pitches) and chaos. Since these nonlinear phenomena are currently widely discussed as integral to mammalian vocalization [Wilden et al., Bioacoustics 9, 171–196 (1988)] or as indicators of vocal pathologies [Herzel et al., J. Speech Hearing Res. 37, 1008–1019 (1994); Riede et al., Z. Sgtkde 62 Suppl: 198–203 (1997)], we sought to understand the production mechanism of the observed vocal instabilities. First the frequency of nonlinear phenomena in the calls was determined for the female and four additional individuals. It turned out that these phenomena appear, but much less frequently in the repertoire of the four other animals. The larynges of the female and two other individuals were dissected post mortem. There was no apparent asymmetry of the vocal folds but a slight asymmetry of the arytenoid cartilages. The most pronounced difference, however, was an upward extension of both vocal folds of the female. This feature is reminiscent of “vocal lips” (syn. “vocal membranes”) in some primates and bats. Spectral analysis of the female’s voice showed clear similarities with an intensively studied voice of a human who produces biphonation intentionally. Finally, the possible communicative relevance of nonlinear phenomena is discussed.