Leveraging Dynamical Symmetries in Two-Dimensional Electronic Spectra to Extract Population Transfer Pathways.

We present a method to deterministically isolate population transfer kinetics from two-dimensional electronic spectroscopic signals. Central to this analysis is the characterization of how all possible subensembles of excited state systems evolve through the population time. When these dynamics are diagrammatically mapped by using double-sided Feynman pathways where population time dynamics are included, a useful symmetry emerges between excited state absorption and ground state bleach recovery dynamics of diagonal and below diagonal cross-peak signals. This symmetry allows removal of pathways from the spectra to isolate signals that evolve according to energy transfer kinetics. We describe a regression procedure to fit to energy transfer time constants and characterize the accuracy of the method in a variety of complex excited state systems using simulated two-dimensional spectra. Our results show that the method is robust for extracting ultrafast energy transfer in multistate excitonic systems, systems containing dark states that affect the signal kinetics, and systems with interfering vibrational relaxation pathways. This procedure can be used to accurately extract energy transfer kinetics from a wide variety of condensed phase systems.

The American Cancer Society's Cancer Prevention Study 3 (CPS-3): Recruitment, study design, and baseline characteristics.

BACKGROUND: Prospective cohort studies contribute importantly to understanding the role of lifestyle, genetic, and other factors in chronic disease etiology. METHODS: The American Cancer Society (ACS) recruited a new prospective cohort study, Cancer Prevention Study 3 (CPS-3), between 2006 and 2013 from 35 states and Puerto Rico. Enrollment took place primarily at ACS community events and at community enrollment "drives." At enrollment sites, participants completed a brief survey that included an informed consent, identifying information necessary for follow-up, and key exposure information. They also provided a waist measure and a nonfasting blood sample. Most participants also completed a more comprehensive baseline survey at home that included extensive medical, lifestyle, and other information. Participants will be followed for incident cancers through linkage with state cancer registries and for cause-specific mortality through linkage with the National Death Index. RESULTS: In total, 303,682 participants were enrolled. Of these, 254,650 completed the baseline survey and are considered "fully" enrolled; they will be sent repeat surveys periodically for at least the next 20 years to update exposure information. The remaining participants (n = 49,032) will not be asked to update exposure information but will be followed for outcomes. Twenty-three percent of participants were men, 17.3% reported a race or ethnicity other than "white," and the median age at enrollment was 47 years. CONCLUSIONS: CPS-3 will be a valuable resource for studies of cancer and other outcomes because of its size; its diversity with respect to age, ethnicity, and geography; and the availability of blood samples and detailed questionnaire information collected over time. Cancer 2017;123:2014-2024. © 2017 American Cancer Society.

Towards Preanalytical Best Practices for Liquid Biopsy Studies: A BLOODPAC Landscape Analysis.

BLOODPAC is a public-private consortium that develops best practices, coordinates clinical and translational research, and manages the BLOODPAC Data Commons to broadly support the liquid biopsy community and accelerate regulatory review to aid patient accessibility. BLOODPAC previously recommended 11 preanalytical minimal technical data elements (MTDEs) for BLOODPAC-sponsored studies and data submitted to BLOODPAC Data Commons. The current landscape analysis evaluates the overlap of the BLOODPAC MTDEs with current best practices, guidelines, and standards documents related to clinical and research liquid biopsy applications. Our findings indicate an existing high degree of concordance among these documents. Where differences exist, the BLOODPAC preanalytical MTDEs can be considered a minimal practicable set for organizations to utilize. These MTDEs were developed following extensive examination of best practices and iterative conversations with the U.S. FDA. BLOODPAC recommends the use of these MTDEs in submissions to data commons and to support liquid biopsy clinical trials and research globally.

Serum 25-hydroxyvitamin D concentrations and postmenopausal breast cancer risk: a nested case control study in the Cancer Prevention Study-II Nutrition Cohort.

INTRODUCTION: Vitamin D status measured during adulthood has been inversely associated with breast cancer risk in some, but not all, studies. Vitamin D has been hypothesized to prevent breast cancer through genomic and non-genomic actions in cell-cycle regulation. METHODS: A subset (n = 21,965) of female participants from the prospective Cancer Prevention Study-II (CPS-II) Nutrition Cohort provided a blood sample from 1998-2001 and were followed through 2005. We measured serum 25-hydroxyvitamin D (25(OH)D) in 516 verified incident cases and 516 controls, matched on birth date (+/- 6 months), date of blood draw (+/- 6 months) and race. Information on medical history, risk factors and lifestyle was available from repeated questionnaires. We computed multi-variable odds ratios (OR) and 95% confidence intervals (95% CI) for the association between 25(OH)D quintile and breast cancer risk using unconditional logistic regression, controlling for matching factors and additional confounders. RESULTS: We observed no association between 25(OH)D and breast cancer (OR = 1.09, 95% CI 0.70-1.68, P = 0.60) for the top vs bottom quintile. Using a priori cut-points, the OR was 0.86 (95% CI 0.59-1.26), for > or =75 vs <50 nmol/L. Results were not different when the first two years of follow-up were excluded, or in analyses stratified by season, latitude, BMI, postmenopausal hormone use, or by tumor grade or estrogen receptor status. CONCLUSIONS: These results do not support an association between adulthood serum 25(OH)D and postmenopausal breast cancer. We cannot rule out an association with 25(OH)D status earlier in life.

Use of blood-pressure-lowering medication and risk of prostate cancer in the Cancer Prevention Study II Nutrition Cohort.

OBJECTIVES: To examine the association between use of anti-hypertensive drugs and prostate cancer incidence among 48,389 men in the Cancer Prevention Study II Nutrition Cohort. METHODS: Proportional hazards models were used to calculate rate ratios (RR) for use of Beta-Blockers (BBs), Calcium Channel Blockers (CCBs), and ACE Inhibitors (ACE) and incident prostate cancer in time-dependent analyses. RESULTS: During follow-up from 1997 to 2005, we identified 3,031 cases of incident prostate cancer. Anti-hypertensive use was associated with slightly decreased risk of all (RR = 0.90, 95% CI 0.83-0.98) and organ-confined low-grade prostate cancer (RR = 0.89, 95% CI 0.81-0.99), but was not statistically significantly associated with aggressive-fatal prostate cancer (RR = 0.93, 95% CI 0.79-1.10). BB and ACE inhibitor treatment was associated with an approximately 10% lower risk for all prostate cancer in models adjusted for age and race. These associations were attenuated and lost statistical significance when adjusted for history of heart disease. No trend with duration of use was detected. CONCLUSIONS: These results do not support the hypothesis that anti-hypertensive medication is strongly associated with risk of prostate cancer. Confounding by concurrent illness may explain inverse associations seen in other studies.

Family history of various cancers and pancreatic cancer mortality in a large cohort.

A family history of pancreatic cancer is associated with increased risk of pancreatic cancer, but uncertainty remains about the magnitude of this association, whether it varies by age or smoking and whether a family history of other cancers may also be associated with increased risk. We examined family history of 14 cancers and pancreatic cancer mortality among ~1.1 million men and women in Cancer Prevention Study-II (CPS-II). CPS-II participants completed a questionnaire at enrollment in 1982. During follow-up through 2006, there were 7,306 pancreatic cancer deaths. A family history of pancreatic cancer in a parent or sibling was associated with pancreatic cancer mortality [multivariable adjusted rate ratio (RR) = 1.66, 95% confidence interval (CI) 1.43-1.94]. This association was stronger among participants aged under 60 (RR = 2.89, 95% CI 1.67-5.02) than among participants aged 60 or older (RR = 1.61, 95% CI 1.37-1.88). Weaker associations were observed for family history of stomach cancer (RR = 1.23, 95% CI 1.11-1.37), liver cancer (RR = 1.25, 95% CI 1.10-1.43), and colorectal cancer (RR = 1.12, 95% CI 1.01-1.23). Results from this large prospective study indicate family history of pancreatic cancer is associated with a moderate increase in risk of pancreatic cancer, and also identify associations with the family history of certain other cancers which may be useful in generating hypotheses about shared risk factors.

Variability of single-leg versus double-leg stance radiographs in the varus knee.

We evaluated measured radiographic parameter variability between single-leg stance (SLS) and double-leg stance (DLS) radiographs in patients with varus knee malalignment, indicated for high tibial osteotomy. Fifty-three consecutive knees (mean, 49 years; range, 18-79 years) were evaluated for varus thrust. SLS and DLS radiographs were obtained. A single blinded observer measured mechanical axis angles and weight-bearing line (WBL) deviation using a goniometer. Mechanical axis angles averaged 9.1 degrees (DLS) and 11.3 degrees (SLS). SLS radiographs averaged 9% greater WBL medialization than did DLS. Medial opening averaged 16.4 mm (DLS) and 18.8 mm (SLS). DLS and SLS radiographs showed no significant differences in patients without varus thrust. Patients with varus thrust demonstrated differences in mechanical axis angles (DLS, 9.4 degrees; SLS, 12.2 degrees), WBL deviation (12.1% less), medialization (DLS), and medial opening necessary for correction (DLS, 16.6 mm; SLS, 20.3 mm). In varus thrust, SLS radiographs more closely replicate dynamic knee malalignment, possibly providing more accurate measurements of angular deformity.

Posterior tibial slope after medial opening wedge high tibial osteotomy of the varus degenerative knee.

This study examined whether medial opening wedge osteotomy inadvertently changes posterior tibial slope and whether this change affects range of motion and functional outcomes. Lateral radiographs of 82 knees with varus arthrosis were reviewed to measure posterior tibial slope before and after medial opening wedge high tibial osteotomy. Anterior or posterior cruciate ligament-deficient knees were excluded. Twenty-one osteotomies were performed using distraction osteogenesis/medial external fixator, 26 using acute distraction/Arthrex plate fixation, and 35 using acute distraction/EBI plate fixation. Preoperative and postoperative Lysholm scores and range of motion were recorded. Posterior slope increased from a mean of 12.5 degrees preoperatively to 16.5 degrees postoperatively (P<.01). Fixation types revealed no difference in posterior slope change. Large slope changes had less preoperative knee flexion than did small changes (123 versus 131; P=.012). No significant correlation existed between posterior slope change and postoperative Lysholm scores (r=0.047, P>.05). We found that medial opening wedge osteotomy may alter sagittal alignment by increasing posterior tibial slope.

Polymorphisms in angiogenesis-related genes and prostate cancer.

BACKGROUND: Angiogenesis is required for development and progression of prostate cancer. Potentially functional single nucleotide polymorphisms (SNP) in genes important in prostate angiogenesis (VEGF, HIF1A, and NOS3) have previously been associated with risk or severity of prostate cancer. METHODS: Prostate cancer cases (n = 1,425) and controls (n = 1,453) were selected from the Cancer Prevention Study II Nutrition Cohort. We examined associations between 58 SNPs in nine angiogenesis-related candidate genes (EGF, LTA, HIF1A, HIF1AN, MMP2, MMP9, NOS2A, NOS3, VEGF) and risk of overall and advanced prostate cancer. Unconditional logistic regression was used to estimate odds ratios, adjusted for matching factors. RESULTS: Our results did not replicate previously observed associations with SNPs in VEGF, HIF1A, or NOS3, nor did we observe associations with SNPs in EGF, LTA, HIF1AN, MMP9, or NOS2A. In the MMP2 gene, three intronic SNPs, all in linkage disequilibrium, were associated with overall and advanced prostate cancer (for overall prostate cancer, P(trend) = 0.01 for rs1477017, P(trend) = 0.01 for rs17301608, P(trend) = 0.02 for rs11639960). However, two of these SNPs (rs17301608 and rs11639960) were examined and were not associated with prostate cancer in a recent genome-wide association study using prostate cancer cases and controls from the Prostate, Lung, Colorectal, and Ovary study cohort. Furthermore, when we pooled our results for these two SNPs with those from the Prostate, Lung, Colorectal, and Ovary cohort; neither SNP was associated with prostate cancer. CONCLUSION: None of the SNPs examined seem likely to be importantly associated with risk of overall or advanced prostate cancer.

Cholesterol-lowering drugs and advanced prostate cancer incidence in a large U.S. cohort.

BACKGROUND: 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors, commonly known as statins, account for the great majority of cholesterol-lowering drug use in the United States. Long-duration statin use was associated with substantially reduced risk of advanced prostate cancer in a recent large prospective study. METHODS: We examined the association between use of cholesterol-lowering drugs and prostate cancer incidence by disease stage and grade among 55,454 men in the Cancer Prevention Study II Nutrition Cohort. Proportional hazards modeling was used to calculate RRs. RESULTS: During follow-up from 1997 to 2003, we identified 3,413 cases of incident prostate cancer, including 317 cases of advanced prostate cancer. After adjustment for age, history of prostate-specific antigen testing, and other potential prostate cancer risk factors, current use of cholesterol-lowering drugs for 5 or more years was not associated with overall prostate cancer incidence (multivariate adjusted rate ratio, 1.06; 95% confidence interval, 0.93-1.20), but was associated with a marginally statistically significant reduction in risk of advanced prostate cancer (rate ratio, 0.60; 95% confidence interval, 0.36-1.00). CONCLUSION: These results provide some support for the hypothesis that long-term statin use is associated with reduced risk of advanced prostate cancer.

Determinants of patient satisfaction with outcome after shoulder arthroplasty.

The purpose of this investigation was to identify the determinants of patient satisfaction with outcome after hemiarthroplasty and total shoulder arthroplasty. Seventy patients who underwent shoulder arthroplasty were studied to determine predictors of patient satisfaction. Patient satisfaction was graded on an ordinal scale from 1 to 10. There was a significant association between patient satisfaction and age (P = .010) and between patient satisfaction and worker's compensation status (P = .018). There was no significant decrease in patient satisfaction for patients with rotator cuff tears. Patient satisfaction was significantly associated with all pain and function variables at follow-up (P < .05). The American Shoulder and Elbow Surgeons score was significantly correlated with patient satisfaction (P = 0.680, P < .05). Independent predictors of satisfaction included pain with activities of daily living, painless use of the arm above the shoulder, and difficulty with toileting (R(2) = 0.555). Subjective variables associated with pain were independent predictors of patient satisfaction. Thus, in assessing patient satisfaction after shoulder arthroplasty, we emphasize the importance of patient-derived subjective assessment of symptoms and function.

Polymorphisms in the vascular endothelial growth factor gene and breast cancer in the Cancer Prevention Study II cohort.

INTRODUCTION: Vascular endothelial growth factor (VEGF) plays a central role in promoting angiogenesis and is over-expressed in breast cancer. At least four polymorphisms in the VEGF gene have been associated with changes in VEGF expression levels: -2578C/A, -1154G/A and -634G/C are all located in the promoter region; and +936C/T is located in the 3'-untranslated region. METHOD: We examined the association between these four VEGF polymorphisms and risk for breast cancer among postmenopausal women in CPS-II (Cancer Prevention Study II) Nutrition Cohort. This cohort was established in 1992 and participants were invited to provide a blood sample between 1998 and 2001. Included in this analysis were 501 postmenopausal women who provided a blood sample and were diagnosed with breast cancer between 1992 and 2001 (cases). Control individuals were 504 cancer-free postmenopausal women matched to the cases with respect to age, race/ethnicity, and date of blood collection (controls). RESULTS: We found no association between any of the polymorphisms examined and overall breast cancer risk. However, associations were markedly different in separate analyses of invasive cancer (n = 380) and in situ cancer (n = 107). The -2578C and -1154G alleles, which are both hypothesized to increase expression of VEGF, were associated with increased risk for invasive breast cancer (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.00-2.14 for -2578 CC versus AA; OR 1.64, 95% CI 1.02-2.64 for -1154 GG versus AA) but they were not associated with risk for in situ cancer. The +936C allele, which is also hypothesized to increase VEGF expression, was not clearly associated with invasive breast cancer (OR 1.21, 95% CI 0.88-1.67 for +936 CC versus TT/CT), but it was associated with reduced risk for in situ cancer (OR 0.59, 95% CI 0.37-0.93 for CC versus TT/CT). The -634 C/G polymorphism was not associated with either invasive or in situ cancer. CONCLUSION: Our findings provide limited support for the hypothesis that the -2578C and -1154G VEGF alleles are associated with increased risk for invasive but not in situ breast cancer in postmenopausal women.

A large cohort study of long-term daily use of adult-strength aspirin and cancer incidence.

BACKGROUND: Epidemiologic evidence indicates that aspirin use is associated with reduced risks of colon cancer and possibly several other cancers, including prostate and breast cancers. Recent results from the Women's Health Study randomized trial indicate that long-term use of low-dose aspirin (100 mg every other day) does not substantially reduce cancer risk. However, the potential effect of long-term daily use of higher doses of aspirin on cancer incidence remains uncertain. METHODS: We examined associations between long-term daily use of adult-strength aspirin (> or = 325 mg/day) and both overall cancer incidence and incidence of 10 types of cancer among 69,810 men and 76,303 women participating in the Cancer Prevention Study II Nutrition Cohort, a relatively elderly population. Aspirin use was reported at enrollment in 1992-1993 and updated in 1997, 1999, and 2001. Multivariable Cox proportional hazards regression was used to calculate rate ratios (RRs). RESULTS: During follow-up through June 2003, 10,931 men and 7196 women were diagnosed with cancer. Long-term (> or = 5 years) daily use of adult-strength aspirin, compared with no use, was associated with lower overall cancer incidence in men (multivariable-adjusted RR = 0.84, 95% confidence interval [CI] = 0.76 to 0.93) and non-statistically significantly lower overall cancer incidence in women (multivariable-adjusted RR = 0.86, 95% CI = 0.73 to 1.03). Overall cancer incidence per 100,000 person-years (standardized to the age distributions of men and women in the study) with long-term daily aspirin use and no aspirin use was 1858 and 2163, respectively, among men and 1083 and 1169, respectively, among women. Long-term daily aspirin use was associated with lower incidence of colorectal cancer (RR = 0.68, 95% CI = 0.52 to 0.90 among men and women combined) and prostate cancer (RR = 0.81, 95% CI = 0.70 to 0.94) and a non-statistically significant lower risk of female breast cancer (RR = 0.83, 95% CI = 0.63 to 1.10). CONCLUSIONS: Long-term daily use of adult-strength aspirin may be associated with modestly reduced overall cancer incidence in populations among whom colorectal, prostate, and breast cancers are common.