bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective Cohort Studies of Vitamin B6 Intake and Colorectal Cancer Incidence: Modification by Time?
Authors: X Zhang , JE Lee , J Ma , Y Je , K Wu , WC Willett , CS Fuchs , EL Giovannucci 
Published: March 2012

Abstract
Background: Vitamin B6 may influence colorectal carcinogenesis through its role in one-carbon metabolism related DNA synthesis and methylation. However, observational studies have been inconclusive and no studies have investigated when in the natural history vitamin B6 intake may prevent colorectal cancer.
Method: We followed 86,440 women in the Nurses' Health Study and 44,410 men in the Health Professionals Follow-up Study for up to 28 years. We assessed vitamin B6 intake every 4 years using validated food frequency questionnaires. We evaluated whether higher vitamin B6 intake in the remote past is strongly associated with a lower risk of colorectal cancer than intake in the recent past. Cox proportional hazards regression models were used to estimate multivariable relative risks (MV RRs, 95%CIs).
Results: Comparing top with bottom quintiles of total vitamin B6 intake, the mean plasma pyridoxal 5–phosphate (PLP, the active form of vitamin B6) levels were 98.3 pmol/mL and 38.9 pmol/mL in women and were 183.2 pmol/mL and 66.0 pmol/mL in men. Total vitamin B6 intake was significantly associated with an approximately 20–30% lower risk of colorectal cancer in age-adjusted results but these significant associations became attenuated and non-significant after adjustment for other colorectal cancer risk factors. Compared extreme quintiles of cumulative intake of total vitamin B6, the MV RRs (95%CIs) for colorectal cancer were 0.98 (0.80, 1.22; P trend = 0.79) in women and 0.98 (0.76, 1.26; P trend = 0.60) in men. For the same comparison, the MV RRs were 0.92 (0.73, 1.16) for total vitamin B6 intake 0–4 year before diagnosis, 0.99 (0.78, 1.26) for intake 4–8 year before diagnosis, 0.93 (0.71, 1.21) for intake 8–12 year before diagnosis, and 0.93 (0.69, 1.26) for intake 12–16 years before diagnosis. The corresponding MV RRs for men were 0.85 (0.63, 1.16), 0.98 (0.70, 1.37), 0.90 (0.63, 1.28), and 1.19 (0.78, 1.83), respectively. Additionally, results did not differ by cancer sub-site, sources of vitamin B6 (food or supplement), or intake of alcohol and folate.
Conclusion: Although a small effect cannot be excluded, our results do not support a strong role of vitamin B6 intake in adulthood in colorectal carcinogenesis among middle-aged U.S. health professionals.
Phenol Xenoestrogens and Mammographic Breast Density
Authors: A Trentham-Dietz , BL Sprague , J Wang , JM Hampton , DSM Buist , E Aiello Bowles , G Sisney , E Burnside , J Hemming , C Hedman 
Published: March 2012

Abstract
Concerns have been raised, largely on the basis of laboratory studies, regarding exposure to phenols, particularly bisphenol-A (BPA), in relation to hormone-related cancers. BPA is present in plastic consumer products including canned food linings and #7 polycarbonate plastics. According to recent NHANES data, human exposure as measured in urine is widespread (about 93% of people aged &gt;5) and more common in females than males (Calafat EHP 2008). Concern regarding BPA in relation to breast cancer risk is based on in vivo and in vitro studies that suggest BPA may have a role in estrogen metabolism and mammary gland development. We examined the cross-sectional association of circulating serum levels of 3 phenols with mammographic breast density - a strong marker for breast cancer risk. A total of 264 postmenopausal women ages 55–70 years with no history of postmenopausal hormone use were recruited from mammography clinics in Madison, Wisconsin. Subjects completed a questionnaire regarding known breast cancer risk factors and provided a blood sample that was analyzed for octylphenol, nonylphenol, and BPA. Percent breast density (mean 15.3%, range 0.4–71.2%) was measured from subjects' mammograms using a computer-assisted thresholding method (Cumulus software). Since phenol levels are higher in the urine than in the serum, as expected many women had undetectable levels of the phenols in their serum: 86.7% octylphenol, 58.7% nonylphenol, and 73.1% BPA. After adjusting for age and body mass index in analysis of variance models, women with detectable serum BPA levels above the median (&gt;0.56 ng/mL; N = 35) had higher percent breast density than women with BPA levels below the median (0.01–0.56 ng/mL; N = 36) and women with no detectable BPA (N = 193) in their serum (17.8% vs. 13.3% vs 12.7%, respectively; P = 0.01). Breast density was not associated with serum levels of either octylphenol or nonylphenol (P = 0.77, P = 0.36, respectively). Given that this study suggests that higher levels of BPA were associated with a clinically-relevant 5% greater breast density, further investigation into the potential influence of BPA on breast cancer risk using human populations is warranted. Supported by DOD BC062649, Komen FAS0703857, and NIH R03 CA139548.
Non-Physician Providers, Cancer Screening and Health Behavior Counseling
Authors: D Kepka , KR Yabroff 
Published: March 2012

Abstract
Purpose: Patients who receive a physician's recommendation for cancer screening and behavioral modification are most likely to comply with these recommendations. However, physicians face time constraints that make it nearly impossible to provide all recommended preventive services. The 2010 Affordable Care Act will expand health insurance coverage to 42 million Americans by 2014. Non-physician providers may help meet this new demand for primary care and ensure compliance with preventive services recommendations.
Methods: Data from the 2005 National Health Interview Survey were analyzed using multivariate logistic regression to assess the association between provider type seen in the past 12 months and compliance with U.S. Preventive Services Task Force cancer screening recommendations and receipt of behavior counseling among age-eligible adults (n = 23,201). Models were adjusted for age, level of education, and insurance status and stratified by gender.
Results: About 15% of NHIS participants (N = 4,652) saw a non-physician provider (nurse practitioner, certified nurse midwife or physician assistant) and a primary care physician. In adjusted analyses, age-eligible women were more likely to be compliant with Pap screening (OR: 5.0; 95% CI: 4.2–5.9), mammography (OR: 6.6; 95% CI: 5.2–8.4) and colorectal screening recommendations (OR: 7.8; 95% CI: 5.3–11.4) if they saw a non-physician provider and a primary care physician compared to not seeing any provider. Similarly, men were more likely to be compliant with colorectal screening recommendations (OR: 9.6; 95% CI: 6.9–13.5) if they saw a non-physician provider and a primary care physician. Women and men were more likely to report a provider asking about smoking status if they saw a non-physician provider and a primary care physician than those who saw other types of healthcare providers ((OR: 2.2; 95% CI: 2.0–2.4) and (OR: 3.0; 95% CI: 2.4–3.7), respectively).
Conclusions: Seeing a non-physician provider and a primary care physician is related to an increased likelihood of compliance with cancer screening recommendations and receipt of health behavior counseling. Opportunities exist for non-physician providers during this era of healthcare reform.
Risk of Non-Hodgkin Lymphoma in Relation to Tricyclic Antidepressant Use
Authors: S Lowry , J Chubak , B McKnight , O Press , N Weiss 
Published: March 2012

Abstract
Purpose: We investigated the relationship between prior use of tricyclic antidepressants (TCA) and risk of non-Hodgkin lymphomas (NHL), both overall and for common subtypes of NHL; previous studies provided some evidence of an association with NHL, but did not assess the risk of specific subtypes of NHL, which have been shown to be etiologically diverse.
Methods: We conducted a population-based matched case-control study among members of Group Health (GH), an integrated healthcare delivery system. Cases included GH members diagnosed with NHL between 1980–2011 at age ≥25 with no record of a prior cancer or of certain autoimmune conditions, who had been enrolled for ≥2 years at the reference date (date of diagnosis). Eight controls were matched to each case on age, sex, enrollment on the reference date, and length of prior enrollment at GH. Information on prior TCA use, including dose, duration, recency, and type, was ascertained from automated pharmacy data. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for NHL (and common subtypes) in relation to various patterns of TCA exposure using conditional logistic regression adjusted for confounders.
Results: We identified 2,768 cases and 22,127 matched controls. We did not observe an appreciably increased risk of NHL among persons who had filled ≥2 TCA prescriptions prior to the reference date compared to those who had filled none (OR: 1.1; 95% CI: 1.0–1.2). Overall risk of NHL was associated to at most a small degree with longer-term use (OR: 1.2; 95% CI: 1.0–1.4 for ≥10 prescriptions), high-dose use (OR: 1.1; 95% CI: 0.8–1.5 for ≥50 mg or equivalent), or use that began more than 5 years prior to reference date (OR: 1.0; 95% CI: 0.9–1.2). TCA use was generally not associated with most major NHL subtypes, though longer-term TCA use was associated with increased risk of chronic lymphocytic leukemia/small lymphocytic lymphoma (OR: 1.5; 95% CI: 1.1–2.0).
Conclusions: We found little evidence that TCA use increases risk of NHL, overall or for specific common subtypes of NHL.
Pharmacokinetics and Safety of Bortezomib in Patients with Advanced Malignancies and Varying Degrees of Liver Dysfunction: Phase I NCI Organ Dysfunction Working Group Study NCI-6432
Authors: LoRusso Patricia M. , Venkatakrishnan Karthik , Ramanathan Ramesh K. , Sarantopoulos John , Mulkerin Daniel , Shibata Stephen I. , Hamilton Anne , Dowlati Afshin , Mani Sridhar , Rudek Michelle A. , Takimoto Chris H. , Neuwirth Rachel , Esseltine Dixie-Lee , Ivy Percy 
Published: March 2012

Abstract
Purpose: The proteasome inhibitor bortezomib undergoes oxidative hepatic metabolism. This study (NCI-6432; NCT00091117) was conducted to evaluate bortezomib pharmacokinetics and safety in patients with varying degrees of hepatic impairment, to inform dosing recommendations in these special populations.
Experimental Design: Patients received bortezomib on days 1, 4, 8, and 11 of 21-day cycles. Patients were assigned to four hepatic function groups based on the National Cancer Institute Organ Dysfunction Working Group classification. Those with normal function received bortezomib at the 1.3 mg/m2 standard dose. Patients with severe, moderate, and mild impairment received escalating doses from 0.5, 0.7, and 1.0 mg/m2, respectively, up to a 1.3 mg/m2 maximum. Serial blood samples were collected for 24 hours postdose on days 1 and 8, cycle 1, for bortezomib plasma concentration measurements.
Results: Sixty-one patients were treated, including 14 with normal hepatic function and 17, 12, and 18 with mild, moderate, and severe impairment, respectively. Mild hepatic impairment did not alter dose-normalized bortezomib exposure (AUC0-tlast) or Cmax compared with patients with normal function. Mean dose-normalized AUC0-tlast was increased by approximately 60% on day 8 in patients with moderate or severe impairment.
Conclusions: Patients with mild hepatic impairment do not require a starting dose adjustment of bortezomib. Patients with moderate or severe hepatic impairment should be started at a reduced dose of 0.7 mg/m2. Clin Cancer Res; 18(10); 2954–63. ©2012 AACR.
Denosumab Dose Selection for Patients with Bone Metastases from Solid Tumors
Authors: Doshi Sameer , Sutjandra Liviawati , Zheng Jenny , Sohn Winnie , Peterson Mark , Jang Graham , Chow Andrew T. , Pérez-Ruixo Juan Jose 
Published: March 2012

Abstract
Purpose: To quantitatively characterize the longitudinal dose exposure–response [urinary N-telopeptide normalized to urinary creatinine (uNTx/Cr) suppression] relationship for denosumab in patients with bone metastases from solid tumors.
Experimental Design: Data from 373 patients who received denosumab as single or multiple subcutaneous doses ranging from 30 to 180 mg (or 0.01 to 3 mg/kg) administered every 4 or 12 weeks for up to 3 years were used in this analysis. An inhibitory sigmoid IMax model was used to characterize the time course of uNTx/Cr as a function of serum denosumab concentrations and the M3 method was used to analyze the 52% of uNTx/Cr values below the limit of quantification in the context of a mixed-effects model. Age, weight, sex, race, and cancer type were evaluated as potential covariates for model parameters. Model-based simulations were undertaken to explore and predict the role of denosumab dose and dosing intervals on uNTx/Cr suppression.
Results: The typical value (between-subject variability; %) for uNTx/Cr at baseline was 49.2 nmol/L/mmol/L (76.8%), denosumab maximal uNTx/Cr suppression (efficacy) was 93.7% (127%), and the denosumab concentration providing half-maximal uNTx/Cr suppression (potency) was 31.8 ng/mL (287%). No effect of covariates on denosumab efficacy and potency was identified. Simulations indicated that a s.c. denosumab dose of 120 mg administered every 4 weeks provides more than 90% suppression of uNTx/Cr in the maximum proportion of patients relative to other every 4- and 12-week doses evaluated.
Conclusions: Over the wide range of dosing regimens examined, a s.c. denosumab dose of 120 mg administered every 4 weeks is the optimal dosing regimen to suppress uNTx/Cr in patients with bone metastases from solid tumors. Clin Cancer Res; 18(9); 2648–57. ©2012 AACR.
Platelet Function Measurement–Based Strategy to Reduce Bleeding and Waiting Time in Clopidogrel-Treated Patients Undergoing Coronary Artery Bypass Graft Surgery
Authors: Mahla Elisabeth , Suarez Thomas A. , Bliden Kevin P. , Rehak Peter , Metzler Helfried , Sequeira Alejandro J. , Cho Peter , Sell Jeffery , Fan John , Antonino Mark J. , Tantry Udaya S. , Gurbel Paul A. 
Published: March 2012

Background—
Aspirin and clopidogrel therapy is associated with a variable bleeding risk in patients undergoing coronary artery bypass graft surgery (CABG). We evaluated the role of platelet function testing in clopidogrel-treated patients undergoing CABG.

Methods and Results—

One hundred eighty patients on background aspirin with/without clopidogrel therapy undergoing elective first time isolated on-pump CABG were enrolled in a prospective single-center, nonrandomized, unblinded investigation (Timing Based on Platelet Function Strategy to Reduce Clopidogrel-Associated Bleeding Related to CABG [TARGET-CABG] study) between September 2008 and January 2011. Clopidogrel responsiveness (ADP-induced platelet-fibrin clot strength [MA
ADP
]) was determined by thrombelastography; CABG was done within 1 day, 3–5 days, and >5 days in patients with an MA
ADP
>50 mm, 35–50 mm, and <35 mm, respectively. The primary end point was 24-hour chest tube drainage and key secondary end point was total number of transfused red blood cells. Equivalence was defined as ≤25% difference between groups. ANCOVA was used to adjust for confounders. Mean 24-hour chest tube drainage in clopidogrel-treated patients was 93% (95% confidence interval, 81–107%) of the amount observed in clopidogrel-naive patients, and the total amount of red blood cells transfused did not differ between groups (1.80 U versus 2.08 U, respectively,
P
=0.540). The total waiting period in clopidogrel-treated patients was 233 days (mean, 2.7 days per patient).

Conclusions—
A strategy based on preoperative platelet function testing to determine the timing of CABG in clopidogrel-treated patients was associated with the same amount of bleeding observed in clopidogrel-naive patients and ≈50% shorter waiting time than recommended in the current guidelines.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00857155.
Spatial Heterogeneity of Air–Sea Energy Fluxes over a Coral Reef—Heron Reef, Australia
Authors: MacKellar Mellissa C. , McGowan Hamish A. , Phinn Stuart R. 
Published: March 2012

AbstractThe thermal environment of a coral reef is moderated by complex interactions of air–sea heat and moisture fluxes, local to synoptic-scale weather and reef hydrodynamics. Measurements of air–sea energy fluxes over coral reefs are essential to understanding the reef–atmosphere processes that underpin coral reef environmental conditions such as water temperature, cloud, precipitation, and local winds (such as during coral bleaching events). Such measurements over coral reefs have been rare, however, and the spatial heterogeneity of surface–atmosphere energy exchanges due to the different geomorphic and biological zones on coral reefs has not been captured. Accordingly, the heterogeneity of coral reefs with regard to substrate, benthic communities, and hydrodynamic processes has not been considered in the characterization of the surface radiation budget and energy balance of coral reefs. Here, the first concurrent in situ eddy covariance measurements of the surface energy balance and radiation transfers over different geomorphic zones of a coral reef are presented. Results showed differences in radiation transfers and sensible and latent heat fluxes over the reef, with higher Bowen ratios over the shallow reef flat zone. The energy flux divergence between sites increased with wind speed and during unstable, southeasterly trade winds with the net flux of heat being positive and negative over different geomorphic zones. The surface drag coefficient at measurement height ranged from 1 × 10−3 to 2.5 × 10−3, with no significant difference between sites. Results confirm that spatial variation in radiation and air–reef–water surface heat and moisture fluxes occurs across a lagoonal platform reef in response to local meteorological conditions, hydrodynamics, and benthic–substrate cover.
Spatiotemporal Characteristics of Drought Occurrences over Japan
Authors: Lee Sang-Min , Byun Hi-Ryong , Tanaka Hiroshi L. 
Published: March 2012

AbstractThe drought climate of Japan from 1902 to 2009 was analyzed using an effective drought index (EDI). Drought regions were identified by hierarchical cluster analysis using drought characteristics (duration, severity, and onset and end dates) obtained from 50 observation stations. The results indicated that droughts could be divided into four groups (G1–G4) that reflected the local climate. The four groups were related to precipitation as follows. The summer rainy season affected groups G2–G4, in which droughts occurred mainly during spring and summer and were relieved before and after the rainy season. The G1 group was not affected by the summer rainy season and droughts were spread evenly throughout the year; it even had cases of droughts relieved by winter snow. All groups included dry conditions over the 108-yr period, and the driest conditions occurred in the late twentieth century. The statistical analysis of drought data showed that a total of 23 country-wide droughts occurred and that the most extreme droughts occurred in 1939–41 and 1984–85, with an EDI of −1.55. In addition, four dry seasons (1939–45, 1997–98, 1994–97, and 2005–09) were found using regime shift analysis. Regional droughts occurred 54, 54, 49, and 59 times in groups G1–G4, respectively. On average, short-term droughts with a duration shorter than 6 months occurred 3.5 times per decade, whereas long-term droughts extending over 1 yr occurred 0.3 times per decade. The drought duration and intensity were used to calculate the statistical return period of country-wide droughts. The 1939–41 drought had the longest return period, at 104.7 yr. The 1987–88 and 1995–97 droughts had return periods of 65.9 and 65.5 yr, respectively.
Evaluation of CO2 Exchange Rates in a Wetland Ecosystem Using the Closed Geosphere Experiment Facility
Authors: Suzuki Shizuo , Yokozawa Masayuki , Inubushi Kazuyuki , Hara Toshihiko , Kimura Michitoshi , Tsuga Shoichi , Tako Yasuhiro , Nakamura Yuji 
Published: March 2012

Abstract
To evaluate annual CO2 exchange rates in a wetland ecosystem, ecosystem respiration rate (Re), net ecosystem productivity (NEP), and gross primary productivity (GPP) were investigated using the Closed Geosphere Experiment Facility (CGEF) located in northeastern Japan. The CGEF is highly airtight and equipped with a Geosphere Module (GM). The GM has a ground area of 5.8 × 8.7 m2 and an average height of 11.9 m, including a soil depth of 3.1 m. A wetland ecosystem dominated by Phragmites australis was introduced into the CGEF. Air temperature and CO2 concentration in the GM were controlled automatically. The hourly nighttime Re increased exponentially with the hourly average air temperature. Both hourly NEP and GPP depended on hourly photosynthetic photon flux density (PPFD). In addition, daily ecosystem CO2 exchange rates (Re, NEP, and GPP) were influenced by above-ground plant biomass. The annual NEP was found to be 64.2 ± 19.2 g C m−2 yr−1 and it resulted from the annual GPP of 555.8 ± 17.0 g C m−2 yr−1 and annual Re of −491.6 ± 15.6 g C m−2 yr−1. Therefore, the wetland ecosystem behaved as a CO2 sink for the entire year. The annual CO2 exchange rates obtained were reasonable values compared to the findings of published studies in P. australis–dominated wild wetlands using the eddy covariance technique and the combined method of internal gas pressures and flow measurements and harvesting.
Probability Distribution of Precipitation Extremes for Weather Index–Based Insurance in the Zhujiang River Basin, South China
Authors: Fischer Thomas , Su Buda , Luo Yong , Scholten Thomas 
Published: March 2012

Abstract
In a changing climate, understanding the frequency of weather extremes is crucial to improving the management of the associated risks. The concept of weather index–based insurance is introduced as a new approach in weather risk adaptation. It can decrease the vulnerability to precipitation extremes that cause floods and economic losses in the Zhujiang River basin. The probability of precipitation extremes is a key input and the probability distribution of annual precipitation extremes is analyzed with four distribution functions [gamma 3, generalized extreme value (GEV), generalized Pareto, and Wakeby]. Three goodness-of-fit tests (Kolmogorov–Smirnov, Anderson–Darling, and Chi Squared) are applied to the distribution functions for annual time series (1961–2007) of 192 meteorological stations. The results show that maximum precipitation and 5-day-maximum precipitation are best described by the Wakeby distribution. On a basin scale, the GEV is the most reliable and robust distribution for estimating precipitation indexes for an index-based insurance program in the Zhujiang River basin. However, each station has to be analyzed individually as GEV is not always the best-fitting distribution function. Based on the distribution functions, spatiotemporal characteristics of return periods for maximum precipitation and 5-day-maximum precipitation are determined. The return levels of the 25- and 50-yr return periods show similar spatial pattern: they are higher in the southeast and lower in the southwest of the basin. This spatial distribution is in line with the annual averages. The statistical distribution of precipitation indexes delivers important information for a theoretical weather index–based insurance program.