Non-steroidal anti-inflammatory drug use, hormone receptor status, and breast cancer-specific mortality in the Carolina Breast Cancer Study.

Epidemiologic studies report a protective association between non-steroidal anti-inflammatory drug (NSAID) use and hormone receptor-positive breast cancer risk, a finding consistent with NSAID-mediated suppression of aromatase-driven estrogen biosynthesis. However, the association between NSAID use and breast cancer-specific mortality is uncertain and it is unknown whether this relationship differs by hormone receptor status. This study comprised 935 invasive breast cancer cases, of which 490 were estrogen receptor (ER)-positive, enrolled between 1996 and 2001 in the Carolina Breast Cancer Study. Self-reported NSAID use in the decade prior to diagnosis was categorized by duration and regularity of use. Differences in tumor size, stage, node, and receptor status by NSAID use were examined using Chi-square tests. Associations between NSAID use and breast cancer-specific mortality were examined using age- and race-adjusted Cox proportional hazards analysis. Tumor characteristics did not differ by NSAID use. Increased duration and regularity of NSAID use was associated with reduced breast cancer-specific mortality in women with ER-positive tumors (long-term regular use (≥8 days/month for ≥ 3 years) versus no use; hazard ratio (HR) 0.48; 95 % confidence interval (CI) 0.23-0.98), with a statistically significant trend with increasing duration and regularity (p-trend = 0.036). There was no association for ER-negative cases (HR 1.19; 95 %CI 0.50-2.81; p-trend = 0.891). Long-term, regular NSAID use in the decade prior to breast cancer diagnosis was associated with reduced breast cancer-specific mortality in ER-positive cases. If confirmed, these findings support the hypothesis that potential chemopreventive properties of NSAIDs are mediated, at least in part, through suppression of estrogen biosynthesis.

Human migration-based graph convolutional network for PM2.5 forecasting in post-COVID-19 pandemic age.

Due to the coronavirus disease 2019 pandemic, local authorities always implanted non-pharmaceutical interventions, such as maintaining social distance to reduce human migration. Besides, previous studies have proved that human migration highly influenced air pollution concentration in an area. Therefore, this study aims to explore whether human migration can work as a significant factor in the post-pandemic age to help PM2.5 concentration forecasting. In this work, we first analyze the variations of PM2.5 in 11 cities of Hubei from 2015 to 2020 and further compare PM2.5 trends with the migration trends of Hubei province in 2020. Experimental results indicate that the human migration indirectly affected the urban PM2.5 concentration. Then, we established a graph data structure based on the migration network describing the migration flow size between any two areas in the Hubei province and proposed a migration attentive graph convolutional network (MAGCN) for forecasting PM2.5. Combined with the migration data. The proposed model can attentively aggregate the information of neighbor nodes through migration weights. Experimental results indicate that the proposed MAGCN can forecast PM2.5 concentration accurately.

Super-spreaders and the rate of transmission of the SARS virus.

We describe a stochastic small-world network model of transmission of the SARS virus. Unlike the standard Susceptible-Infected-Removed models of disease transmission, our model exhibits both geographically localised outbreaks and "super-spreaders". Moreover, the combination of localised and long range links allows for more accurate modelling of partial isolation and various public health policies. From this model, we derive an expression for the probability of a widespread outbreak and a condition to ensure that the epidemic is controlled. Moreover, multiple simulations are used to make predictions of the likelihood of various eventual scenarios for fixed initial conditions. The main conclusions of this study are: (i) "super-spreaders" may occur even if the infectiousness of all infected individuals is constant; (ii) consistent with previous reports, extended exposure time beyond 3-5 days (i.e. significant nosocomial transmission) was the key factor in the severity of the SARS outbreak in Hong Kong; and, (iii) the spread of SARS can be effectively controlled by either limiting long range links (imposing a partial quarantine) or enforcing rapid hospitalisation and isolation of symptomatic individuals.

Clustering model for transmission of the SARS virus: application to epidemic control and risk assessment.

We propose a new four state model for disease transmission and illustrate the model with data from the 2003 SARS epidemic in Hong Kong. The critical feature of this model is that the community is modelled as a small-world network of interconnected nodes. Each node is linked to a fixed number of immediate neighbors and a random number of geographically remote nodes. Transmission can only propagate between linked nodes. This model exhibits two features typical of SARS transmission: geographically localized outbreaks and "super-spreaders". Neither of these features are evident in standard susceptible-infected-removed models of disease transmission. Our analysis indicates that "super-spreaders" may occur even if the infectiousness of all infected individuals is constant. Moreover, we find that nosocomial transmission in Hong Kong directly contributed to the severity of the outbreak and that by limiting individual exposure time to 3-5 days the extent of the SARS epidemic would have been minimal.

Glutathione S-transferases M1, T1, and P1 and breast cancer.

We examined associations for glutathione S-transferases M1 (GSTM1), T1 (GSTT1), and P1 (GSTP1) genotypes and breast cancer in the Carolina Breast Cancer Study, a population-based, case-control study in North Carolina. Odds ratios were close to the null value for each GST locus among African-American women (278 cases and 271 controls) and white women (410 cases and 392 controls), as well as pre- and postmenopausal women. For women with a history of breast cancer in one or more first-degree relatives, odds ratios were 2.1 (95% confidence interval, 1.0-4.2) for GSTM1 null and 1.9 (0.8-4.6) for GSTT1 null genotypes. Among women with a family history, age at diagnosis was significantly earlier for those with the GSTM1 null genotype. We did not observe strong evidence for modification of odds ratios for smoking according to GST genotypes. There was no evidence for combined effects of GSTM1, GSTT1, and GSTP1 genotypes, and there were no combined effects for GST genotypes and the catechol O-methyltransferase genotype. We conclude that GSTM1, GSTT1, and GSTP1 genotypes do not play a strong role in susceptibility to breast cancer. However, the role of GST genotypes in age at onset and risk of breast cancer among women with a family history merits further investigation.

Dichlorodiphenyldichloroethene, polychlorinated biphenyls, and breast cancer among African-American and white women in North Carolina.

We examined plasma dichlorodiphenyldichloroethene (DDE) and total polychlorinated biphenyl (PCB) levels in relation to breast cancer in a population-based, case-control study of African-American women (292 cases and 270 controls) and white women (456 cases and 389 controls) in North Carolina. Adjusted odds ratios (ORs) for breast cancer comparing the highest to lowest third of DDE were 1.41 [95% confidence interval (CI), 0.87-2.29] in African-American women and 0.98 (95% CI, 0.67-1.43) in white women. ORs comparing the highest to lowest third of total PCBs were 1.74 (95% CI, 1.00-3.01) in African-American women and 1.03 (95% CI, 0.68-1.56) in white women. Among African-Americans, the OR for total PCBs was highest for obese women (body mass index 234.2; OR, 4.92; 95% CI, 1.63-14.83). In contrast, the OR for DDE was highest for the leanest African-American women (body mass index, <25; OR, 3.84; 95% CI, 0.98-15.08). ORs for DDE were not elevated among women who lived or worked on farms or elevated among farming women who reported exposure to pesticides. Our results suggest absence of a strong effect for DDE or total PCBs in breast cancer but lend support for associations among subgroups of women. In our study, factors such as income, parity, breastfeeding, race/ethnicity, and body mass index influenced the relationship of organochlorines and breast cancer. Differing distributions of such factors may explain some of the inconsistencies across previous studies.

Cigarette smoking, N-acetyltransferases 1 and 2, and breast cancer risk.

To examine the effects of smoking and N-acetylation genetics on breast cancer risk, we analyzed data from an ongoing, population-based, case-control study of invasive breast cancer in North Carolina. The study population consisted of 498 cases and 473 controls, with approximately equal numbers of African-American and white women, and women under the age of 50 and age 50 years or older. Among premenopausal women, there was no association between current smoking [odds ratio (OR), 0.9; 95% confidence interval (CI), 0.5-1.5] or past smoking (OR, 1.0; 95% CI, 0.6-1.6) and breast cancer risk. Among postmenopausal women, there was also no association with current smoking (OR, 1.2; 95% CI, 0.7-2.0); however, a small increase in risk was observed for past smoking (OR, 1.5; 95% CI, 1.0-2.4). For postmenopausal women who smoked in the past, ORs and 95% CIs were 3.4 (1.4-8.1) for smoking within the past 3 years, 3.0 (1.3-6.7) for smoking 4-9 years ago, and 0.6 (0.3-1.4) for smoking 10-19 years ago. Neither N-acetyltransferase 1 (NAT1) nor N-acetyltransferase 2 (NAT2) genotype alone was associated with increased breast cancer risk. There was little evidence for modification of smoking effects according to genotype, except among postmenopausal women. Among postmenopausal women, ORs for smoking within the past 3 years were greater for women with the NAT1*10 genotype (OR, 9.0; 95% CI, 1.9-41.8) than NAT1-non*10 (OR, 2.5; 95% CI, 0.9-7.2) and greater for NAT2-rapid genotype (OR, 7.4; 95% CI, 1.6-32.6) than NAT2-slow (OR, 2.8; 95% CI, 0.4-8.0). Future studies of NAT genotypes and breast cancer should investigate the effects of environmental tobacco smoke, diet, and other exposures.

Polymorphisms in the DNA repair gene XRCC1 and breast cancer.

X-ray repair cross complementing group 1 (XRCC1) encodes a protein involved in base excision repair. We examined the association of polymorphisms in XRCC1 (codon 194 Arg-->Trp and codon 399 Arg-->Gln) and breast cancer in the Carolina Breast Cancer Study, a population-based case-control study in North Carolina. No association was observed between XRCC1 codon 194 genotype and breast cancer, and odds ratios (ORs) were not modified by smoking or radiation exposure. A positive association for XRCC1 codon 399 Arg/Gln or Gln/Gln genotypes compared with Arg/Arg was found among African Americans (253 cases, 266 controls; OR = 1.7, 95% confidence interval, 1.1-2.4) but not whites (386 cases, 381 controls; OR =1.0, 95% confidence interval, 0.8-1.4). Among African-American women, ORs for the duration of smoking were elevated among women with XRCC1 codon 399 Arg/Arg genotype (trend test; P < 0.001) but not Arg/Gln or Gln/Gln (P = 0.23). There was no difference in OR for smoking according to XRCC1 codon 399 genotype in white women. ORs for occupational exposure to ionizing radiation were stronger for African-American and white women with codon 399 Arg/Arg genotype. High-dose radiation to the chest was more strongly associated with breast cancer among white women with XRCC1 codon 399 Arg/Arg genotype. Our results suggest that XRRC1 codon 399 genotype may influence breast cancer risk, perhaps by modifying the effects of environmental exposures. However, interpretation of our results is limited by incomplete knowledge regarding the biological function of XRCC1 alleles.

Male and female occupation in relation to miscarriage and preterm delivery in central North Carolina.

PURPOSE: This study was undertaken to evaluate the role of parental occupation in miscarriage and preterm delivery. Previous studies raise the possibility that both male and female exposures could affect pregnancy. METHODS: Data from a population-based study of miscarriage and preterm delivery in central North Carolina were used to examine potential associations with male and female occupation. Medically treated miscarriage cases (n = 418), preterm delivery cases identified through hospital record review (n = 582), and term, normal birth weight controls (n = 787) were sought for telephone interview. The interview included information on jobs the woman held before and during the pregnancy, reports of her partner's job around the time of pregnancy, and information on potential confounding factors. RESULTS: Female employment overall, or in specific jobs, around the time of conception or early pregnancy was not associated with the risk of miscarriage, whereas working during pregnancy, especially in the seventh month, was inversely associated with risk of preterm delivery. Male employment in several industrial occupations was weakly associated with miscarriage (adjusted odds ratios (OR) of 1.6 to 1.8), and somewhat more strongly associated with preterm delivery, particularly for chemists and sheet metal workers (adjusted OR over 3). Restriction to married men strengthened the associations. CONCLUSIONS: Our results are limited by nonresponse, imprecision, incomplete identification of miscarriages, and lack of detailed occupational exposure information. Nonetheless, we found greater support for further examination of male compared to female jobs in relation to pregnancy outcome.

Participation rates in a case-control study: the impact of age, race, and race of interviewer.

PURPOSE: Despite concerns about declining participation rates in epidemiologic studies in recent years, relatively few papers have discussed obstacles to recruiting study participants or strategies for optimizing response rates. This report describes factors associated with nonparticipation in a population-based, case-control study of breast cancer and discusses ways to overcome barriers to participation. METHODS: Contact and cooperation rates were calculated for participants in the Carolina Breast Cancer Study (CBCS), stratified by case status, age, race, and race of interviewer. Demographic and breast cancer risk factor characteristics of partial and full responders also were compared. RESULTS: Contact rates and cooperation rates varied by case/control status and demographic characteristics. Contact rates were lower among controls, younger women, and black women. Cooperation rates were lower among controls, older women, and black cases. Cooperation rates were higher among both black and nonblack women when participants and interviewers were concordant on race. CONCLUSIONS: Obstacles to recruitment seem to differ among race and age subgroups, suggesting that recruitment strategies may need to be tailored to potential participants based upon demographic characteristics. Strategies have been implemented to improve response rates in this and other epidemiologic studies; however, additional research and innovation in this area are needed.

Effects on the immune system associated with living near a pesticide dump site.

In this paper, we report results of the second phase of a larger study designed to evaluate the effects on the immune system of living near a Superfund site containing organochlorine pesticides, volatile organic compounds, and metals. Phase II was conducted to determine whether living near the site, consisting of six locations in Aberdeen, North Carolina, is associated with higher plasma organochlorine levels, immune suppression, or DNA damage. Each of 302 residents of Aberdeen and neighboring communities provided a blood specimen, underwent a skin test, and answered a questionnaire. Blood specimens were analyzed for organochlorine pesticides, immune markers, and micronuclei. Of 20 organochlorines tested, only DDE was detected in the blood of participants (except for one individual). Age-adjusted mean plasma DDE levels were 4.05 ppb for Aberdeen residents and 2.95 ppb (p = 0.01) for residents of neighboring communities. Residents of 40-59 years of age who lived within a mile of any site, but particularly the Farm Chemicals site, had higher plasma DDE levels than residents who lived farther away. Residents who lived near the Farm Chemicals site before versus after 1985 also had higher plasma DDE levels. Overall, there were few differences in immune markers between residents of Aberdeen and the neighboring communities. However, residents who lived closer to the dump sites had statistically significantly lower mitogen-induced lymphoproliferative activity than residents who lived farther away (p < 0.05). Residential location was not consistently associated with frequency of micronuclei or skin test responses. Although some statistically significant differences in immune markers were noted in association with residential location, the magnitude of effects are of uncertain clinical importance.

Quality of life and functional health of primary care patients.

Quality of life and functional health were measured cross-sectionally for 314 adult ambulatory primary care patients in a rural clinic and found to be much better for patients with low severity of illness who required no confinement to home because of health problems, than for patients with high severity of illness who required confinement. Severity of illness was the strongest predictor for patient-reported physical health function and for patient quality of life when assessed by the health provider. Confinement was the strongest predictor for patient quality of life when assessed by the patient. There was very little agreement between patient-assessed and provider-assessed quality of life. Family stress was the strongest predictor of function in terms of mental health, social health, general health, self-esteem, anxiety, and depression. These data suggest that clinicians should direct increased attention to patient-assessed quality of life, patient-reported functional health status, and psychosocial factors such as family stress in an effort to improve medical outcomes.

Anxiety and depressive symptom identification using the Duke Health Profile.

Duke Health Profile (DUKE) subscales were compared for their ability to identify anxiety and depressive symptoms as measured by the State Anxiety Inventory (SAI) and the Center for Epidemiologic Studies Depression Scale (CES-D) in 413 primary care patients. The seven-item Duke Anxiety-Depression Scale (DUKE-AD) was the best symptom identifier, with sensitivities and specificities greater than 70% for high scores on both the SAI and CES-D. Also, baseline DUKE-AD scores predicted five clinical outcomes during an 18-month follow-up period, with receiver operating characteristic (ROC) curve areas ranging from 57.1 to 58.7%. Patients shown by DUKE-AD scores to be at high risk (>30, scale 0-100) for symptoms of anxiety and/or depression were more often women, less well-educated, not working, and with lower socioeconomic status. The severity of illness was higher than that of low-risk patients. Although the providers did not know which patients were at high risk, they made a clinical diagnosis of anxiety or depression more often in high-risk patients.

The Duke Severity of Illness Checklist (DUSOI) for measurement of severity and comorbidity.

The Duke Severity of Illness Checklist (DUSOI) was evaluated on 414 primary care adult patients using data collected both by medical providers at the time of the patient visit and later by a chart auditor. Severity scores for individual diagnoses were determined by summing the ratings for four non-disease-specific parameters: symptom level, complications, prognosis without treatment, and expected response to treatment. Mean diagnosis severity scores (scale 0-100) among the 21 most prevalent diagnoses varied from a low of 13.9 for menopausal syndrome to a high of 43.0 for sprains and strains. An overall severity score was calculated by combining diagnosis severity scores and giving highest weights to the most severe diagnoses. Provider-generated overall severity scores (mean = 43.3) and auditor-generated overall severity scores (mean = 38.9) were significantly correlated (coefficient of agreement = 0.59, p < 0.0001). Diagnoses varied in their individual contribution to the overall severity score, from 8.9% for lipid disorder to 90.0% for sprains and strains. Separate comorbidity severity scores were calculated to measure the severity of all of each patient's health problems except the diagnosis under study. For example, patients with menopausal syndrome had co-existing health problems which generated a high mean comorbidity severity score of 43.2, while patients with sprains and strains had a low mean comorbidity score of 4.7. The DUSOI Checklist can be used in the clinical setting by both providers and auditors to produce quantitative severity scores (by diagnosis, overall, and for comorbidity) which are based entirely upon clinical judgment. This method should be useful in controlling for severity of illness in clinical studies and indicating the outcome of medical care in terms of reduction in severity of illness following medical interventions.

Cigarette smoking and semen quality.

OBJECTIVE: To determine whether cotinine levels provide stronger evidence for an association between smoking and semen quality than the number of cigarettes smoked per day or years smoked controlling for potential confounders and effect modifiers. DESIGN: Cross-sectional study. SETTING: Male volunteers at the Reproductive Endocrinology-Fertility Laboratory. PARTICIPANTS: Eighty-eight men (ages 18 to 35 years) provided a semen, urine, and blood specimen and completed a self-administered questionnaire concerning smoking and demographic information as well as caffeine and alcohol consumption. Urine, blood, and semen cotinine levels were analyzed via RIA. MAIN OUTCOME MEASURE: Standard clinical semen analysis. RESULTS: Number of cigarettes smoked per day, years smoked, and log-transformed cotinine levels were associated negatively with semen quality (density, total count, and motility). The association was evident among men age > or = 22 years. For example, the correlation coefficient for the overall association between logged urine cotinine and logged sperm density was -0.23; those stratified by age were 0. 13 (age < 22 years) and - 0. 39 (age > or = 22 years). Potential confounders included in regression models did not diminish the associations. CONCLUSIONS: Smoking is associated with lowered semen quality.

Actions of beta-bungarotoxin on spontaneous release of transmitter at muscle end-plates treated with botulinum toxin.

Rat leg muscles were injected subcutaneously with sublethal doses of type A botulinum neurotoxin, and the extensor digitorum longus muscle removed three days later. Intracellular microelectrode recordings were then made of miniature end-plate potentials (mepps). The mepp frequency was reduced by botulinum toxin, while mepp rise times were slowed. Mepp amplitude distributions became characteristically skew. beta-Bungarotoxin (140 nM) was applied to normal muscles in vitro and recordings were made 10-30 min later. The main effect was an increase in mepp frequency during this period. Mepp rise times were unaffected. When beta-bungarotoxin was applied in vitro to muscles treated with botulinum toxin there was also an increase in mepp frequency, although to a value less than in normal muscles. The mepp rise times were speeded up to normal values. The mepp amplitude and rise time distributions showed no obvious evidence for the addition of a second component to the distribution. The data appear to support the hypothesis that the sites for spontaneous release in botulinised muscle may be located at or near the usual release sites at the active zones.

Localization of sites for 125I-labelled botulinum neurotoxin at murine neuromuscular junction and its binding to rat brain synaptosomes.

Botulinum neurotoxin, purified to homogeneity from Clostridium botulinum (Type A), was found to be highly neurotoxic (greater than 8 X 10(7) mouse LD50/mg protein). Labelling of this pure neurotoxin with 125I-iodine to high specific radioactivity was achieved without appreciable loss of biological activity. This was used to demonstrate saturable binding sites for this toxin at the neuromuscular junction, following in vivo administration into mice. A demonstrable inhibitory effect of the neurotoxin on release of acetylcholine from rat cerebrocortical synaptosomes indicates that it affects synapses in the central nervous system. Kinetic studies on the binding of 125I-labelled neurotoxin to brain synaptosomes yielded an association rate constant of 2.3 x 10(5)M-1s-1; dissociation plots were biphasic and the predominant species showed a rate constant of 1.2 X 10(-4)s-1. The saturable binding component is heat-sensitive and inactivated by trypsin. Preliminary studies showed that botulinum neurotoxin associates with plasma membrane fractions of synaptosomes and that binding does not result in any gross structural changes, at least in the majority of the toxin molecules.

The health status and life satisfaction of first-year medical students.

The self-reported health status and life satisfaction of 286 first-year Duke University medical students in four consecutive classes were measured at the beginning and end of the school year and compared statistically with relevant sociodemographic and behavioral factors. Health status, quantitated in terms of Duke Health Profile scores, was generally lower for women than for men. Although there was a definite trend of worsening along all parameters of health and satisfaction during the year for both women and men, the most marked change was the increase in depressive symptoms. The students who were very satisfied with life had fewer symptoms of depression and anxiety; higher self-esteem, better physical, mental, and social health; stronger social ties; more physical activity; more sleep; and fewer stressful life events. Strong social ties was the factor most positively related to better health and life satisfaction.

Minimum description length neural networks for time series prediction.

Artificial neural networks (ANN) are typically composed of a large number of nonlinear functions (neurons) each with several linear and nonlinear parameters that are fitted to data through a computationally intensive training process. Longer training results in a closer fit to the data, but excessive training will lead to overfitting. We propose an alternative scheme that has previously been described for radial basis functions (RBF). We show that fundamental differences between ANN and RBF make application of this scheme to ANN nontrivial. Under this scheme, the training process is replaced by an optimal fitting routine, and overfitting is avoided by controlling the number of neurons in the network. We show that for time series modeling and prediction, this procedure leads to small models (few neurons) that mimic the underlying dynamics of the system well and do not overfit the data. We apply this algorithm to several computational and real systems including chaotic differential equations, the annual sunspot count, and experimental data obtained from a chaotic laser. Our experiments indicate that the structural differences between ANN and RBF make ANN particularly well suited to modeling chaotic time series data.