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"McCullough, Cynthia S"
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American Cancer Society Guideline for Diet and Physical Activity for Cancer Prevention
by
Grant, Barbara L
,
Bandera, Elisa V
,
Rock, Cheryl L
in
Activity patterns
,
Cancer
,
Cardiovascular disease
2020
The American Cancer Society (ACS) publishes the Diet and Physical Activity Guideline to serve as a foundation for its communication, policy, and commu-nity strategies and, ultimately, to affect dietary and physical activity patterns among Americans. This guideline is developed by a national panel of experts in cancer re-search, prevention, epidemiology, public health, and policy, and reflects the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS guideline focuses on recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or creates barriers to healthy behaviors. Therefore, this com-mittee presents recommendations for community action to accompany the 4 recom-mendations for individual choices to reduce cancer risk. These recommendations for community action recognize that a supportive social and physical environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. This 2020 ACS guideline is consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes as well as for general health promotion, as defined by the 2015 to 2020 Dietary Guidelines for Americans and the 2018 Physical Activity Guidelines for Americans.
Journal Article
The Development of Regional Dialect Locality Judgments and Language Attitudes Across the Life Span
2019
The development of language attitudes and perception of talker regional background was investigated across the life span (N = 240, age range = 4-75 years). Participants rated 12 talkers on dimensions of geographic locality, status, and solidarity. Children could classify some dialects by locality by age 6-7 years and showed adult-like patterns by age 8 years. Children showed adult-like status ratings for some dialects by age 4r-5 years but were not fully adult-like until age 12 years. Solidarity ratings were more variable and did not exhibit a clear developmental trajectory, although some adult-like patterns were in place by age 6-7 years. Locality ratings were a significant but modest predictor of attitude ratings, suggesting that geographic knowledge is one contributor to language attitudes throughout development.
Journal Article
Validation of the accuracy of the FAST™ score for detecting patients with at-risk nonalcoholic steatohepatitis (NASH) in a North American cohort and comparison to other non-invasive algorithms
2022
Management of patients with NASH who are at elevated risk of progressing to complications of cirrhosis (at-risk NASH) would be enhanced by an accurate, noninvasive diagnostic test. The new FAST™ score, a combination of FibroScan® parameters liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) and aspartate aminotransferase (AST), has shown good diagnostic accuracy for at-risk NASH (area-under-the-Receiver-Operating-Characteristic [AUROC] = 0.80) in European cohorts. We aimed to validate the FAST™ score in a North American cohort and show how its diagnostic accuracy might vary by patient mix. We also compared the diagnostic performance of FAST™ to other non-invasive algorithms for the diagnosis of at-risk NASH.
We studied adults with biopsy-proven non-alcoholic fatty liver disease (NAFLD) from the multicenter NASH Clinical Research Network (CRN) Adult Database 2 (DB2) cohort study. At-risk-NASH was histologically defined as definite NASH with a NAFLD Activity Score (NAS) ≥ 4 with at least 1 point in each category and a fibrosis stage ≥ 2. We used the Echosens® formula for FAST™ from LSM (kPa), CAP (dB/m), and AST (U/L), and the FAST™-based Rule-Out (FAST™ ≤ 0.35, sensitivity = 90%) and Rule-In (FAST™ ≥ 0.67, specificity = 90%) zones. We determined the following diagnostic performance measures: AUROC, sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV); these were calculated for the total sample and by subgroups of patients and by FibroScan® exam features. We also compared the at-risk NASH diagnostic performance of FAST™ to other non-invasive algorithms: NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4) index, and AST to platelet ratio index (APRI).
The NASH CRN population of 585 patients was 62% female, 79% white, 14% Hispanic, and 73% obese; the mean age was 51 years. The mean (SD) AST and ALT were 50 (37) U/L and 66 (45) U/L, respectively. 214 (37%) had at-risk NASH. The AUROC of FAST™ for at-risk NASH in the NASH CRN study population was 0.81 (95% CI: 0.77, 0.84. Using FAST™-based cut-offs, 35% of patients were ruled-out with corresponding NPV = 0.90 and 27% of patients were ruled-in with corresponding PPV = 0.69. The diagnostic accuracy of FAST™ was higher in non-whites vs. whites (AUROC: 0.91 vs 0.78; p = 0.001), and in patients with a normal BMI vs. BMI > 35 kg/m2 (AUROC: 0.94 vs 0.78, p = 0.008). No differences were observed by other patient characteristics or FibroScan® exam features. The FAST™ score had higher diagnostic accuracy than other non-invasive algorithms for the diagnosis of at-risk NASH (AUROC for NFS, FIB-4, and APRI 0.67, 0.73, 0.74, respectively).
We validated the FAST™ score for the diagnosis of at-risk NASH in a large, multi-racial population in North America, with a prevalence of at-risk NASH of 37%. Diagnostic performance varies by subgroups of NASH patients defined by race and obesity. FAST™ performed better than other non-invasive algorithms for the diagnosis of at-risk NASH.
Journal Article
American Cancer Society nutrition and physical activity guideline for cancer survivors
by
Neuhouser, Marian L
,
Thomson, Cynthia A
,
Nekhlyudov, Larissa
in
Cancer
,
Clinical trials
,
Complications
2022
The overall 5-year relative survival rate for all cancers combined is now 68%, and there are over 16.9 million survivors in the United States. Evidence from laboratory and observational studies suggests that factors such as diet, physical activity, and obesity may affect risk for recurrence and overall survival after a cancer diagnosis. The purpose of this American Cancer Society guideline is to provide evidence-based, cancer-specific recommendations for anthropometric parameters, physical activity, diet, and alcohol intake for reducing recurrence and cancer-specific and overall mortality. The audiences for this guideline are health care providers caring for cancer survivors as well as cancer survivors and their families. The guideline is intended to serve as a resource for informing American Cancer Society programs, health policy, and the media. Sources of evidence that form the basis of this guideline are systematic literature reviews, meta-analyses, pooled analyses of cohort studies, and large randomized clinical trials published since 2012. Recommendations for nutrition and physical activity during cancer treatment, informed by current practice, large cancer care organizations, and reviews of other expert bodies, are also presented. To provide additional context for the guidelines, the authors also include information on the relationship between health-related behaviors and comorbidities, long-term sequelae and patient-reported outcomes, and health disparities, with attention to enabling survivors' ability to adhere to recommendations. Approaches to meet survivors' needs are addressed as well as clinical care coordination and resources for nutrition and physical activity counseling after a cancer diagnosis.
Journal Article
FACT and Ubp10 collaborate to modulate H2B deubiquitination and nucleosome dynamics
by
Morgan, Michael T
,
McCullough, Laura
,
Wolberger, Cynthia
in
Alleles
,
Biochemistry and Chemical Biology
,
Biophysics
2019
Monoubiquitination of histone H2B (H2B-Ub) plays a role in transcription and DNA replication, and is required for normal localization of the histone chaperone, FACT. In yeast, H2B-Ub is deubiquitinated by Ubp8, a subunit of SAGA, and Ubp10. Although they target the same substrate, loss of Ubp8 and Ubp10 cause different phenotypes and alter the transcription of different genes. We show that Ubp10 has poor activity on yeast nucleosomes, but that the addition of FACT stimulates Ubp10 activity on nucleosomes and not on other substrates. Consistent with a role for FACT in deubiquitinating H2B in vivo, a FACT mutant strain shows elevated levels of H2B-Ub. Combination of FACT mutants with deletion of Ubp10, but not Ubp8, confers increased sensitivity to hydroxyurea and activates a cryptic transcription reporter, suggesting that FACT and Ubp10 may coordinate nucleosome assembly during DNA replication and transcription. Our findings reveal unexpected interplay between H2B deubiquitination and nucleosome dynamics.
Journal Article
Alcohol intake and pancreatic cancer risk: An analysis from 30 prospective studies across Asia, Australia, Europe, and North America
by
Jayasekara, Harindra
,
Koh, Woon-Puay
,
Platz, Elizabeth A.
in
Adult
,
Aged
,
Alcohol Drinking - adverse effects
2025
Alcohol is a known carcinogen, yet the evidence for an association with pancreatic cancer risk is considered as limited or inconclusive by international expert panels. We examined the association between alcohol intake and pancreatic cancer risk in a large consortium of prospective studies.
Population-based individual-level data was pooled from 30 cohorts across four continents, including Asia, Australia, Europe, and North America. A total of 2,494,432 participants without cancer at baseline (62% women, 84% European ancestries, 70% alcohol drinkers [alcohol intake ≥ 0.1 g/day], 47% never smokers) were recruited between 1980 and 2013 at the median age of 57 years and 10,067 incident pancreatic cancer cases were recorded. In age- and sex-stratified Cox proportional hazards models adjusted for smoking history, diabetes status, body mass index, height, education, race and ethnicity, and physical activity, pancreatic cancer hazard ratios (HR) and 95% confidence intervals (CI) were estimated for categories of alcohol intake and in continuous for a 10 g/day increase. Potential heterogeneity by sex, smoking status, geographic regions, and type of alcoholic beverage was investigated. Alcohol intake was positively associated with pancreatic cancer risk, with HR30-to-<60 g/day and HR≥60 g/day equal to 1.12 (95% CI [1.03,1.21]) and 1.32 (95% CI [1.18,1.47]), respectively, compared to intake of 0.1 to <5 g/day. A 10 g/day increment of alcohol intake was associated with a 3% increased pancreatic cancer risk overall (HR: 1.03; 95% CI [1.02,1.04]; pvalue < 0.001) and among never smokers (HR: 1.03; 95% CI [1.01,1.06]; pvalue = 0.006), with no evidence of heterogeneity by sex (pheterogeneity = 0.274) or smoking status (pheterogeneity = 0.624). Associations were consistent in Europe-Australia (HR10 g/day = 1.03, 95% CI [1.00,1.05]; pvalue = 0.042) and North America (HR10 g/day = 1.03, 95% CI [1.02,1.05]; pvalue < 0.001), while no association was observed in cohorts from Asia (HR10 g/day = 1.00, 95% CI [0.96,1.03]; pvalue = 0.800; pheterogeneity = 0.003). Positive associations with pancreatic cancer risk were found for alcohol intake from beer (HR10 g/day = 1.02, 95% CI [1.00,1.04]; pvalue = 0.015) and spirits/liquor (HR10 g/day = 1.04, 95% CI [1.03,1.06]; pvalue < 0.001), but not wine (HR10 g/day = 1.00, 95% CI [0.98,1.03]; pvalue = 0.827). The differential associations across geographic regions and types of alcoholic beverages might reflect differences in drinking habits and deserve more investigations.
Findings from this large-scale pooled analysis support a modest positive association between alcohol intake and pancreatic cancer risk, irrespective of sex and smoking status. Associations were particularly evident for baseline alcohol intake of at least 15 g/day in women and 30 g/day in men.
Journal Article
Association of Histologic Disease Activity With Progression of Nonalcoholic Fatty Liver Disease
by
Tonascia, James
,
Kleiner, David E.
,
Dasarathy, Srinivasan
in
Academic Medical Centers
,
Adult
,
Aspartate Aminotransferases - analysis
2019
The histologic evolution of the full spectrum of nonalcoholic fatty liver disease (NAFLD) and factors associated with progression or regression remain to be definitively established.
To evaluate the histologic evolution of NAFLD and the factors associated with changes in disease severity over time.
A prospective cohort substudy from the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) NAFLD Database study, a noninterventional registry, was performed at 8 university medical research centers. Masked assessment of liver histologic specimens was performed, using a prespecified protocol to score individual biopsies. Participants included 446 adults with NAFLD enrolled in the NASH CRN Database studies between October 27, 2004, and September 13, 2013, who underwent 2 liver biopsies 1 or more year apart. Data analysis was performed from October 2016 to October 2018.
Progression and regression of fibrosis stage, using clinical, laboratory, and histologic findings, including the NAFLD activity score (NAS) (sum of scores for steatosis, lobular inflammation, and ballooning; range, 0-8, with 8 indicating more severe disease).
A total of 446 adults (mean [SD] age, 47 [11] years; 294 [65.9%] women) with NAFLD (NAFL, 86 [19.3%]), borderline NASH (84 [18.8%]), and definite NASH (276 [61.9%]) were studied. Over a mean (SD) interval of 4.9 (2.8) years between biopsies, NAFL resolved in 11 patients (12.8%) and progressed to steatohepatitis in 36 patients (41.9%). Steatohepatitis resolved in 24 (28.6%) of the patients with borderline NASH and 61 (22.1%) of those with definite NASH. Fibrosis progression or regression by at least 1 stage occurred in 132 (30%) and 151 [34%] participants, respectively. Metabolic syndrome (20 [95%] vs 108 [72%]; P = .03), baseline NAS (mean [SD], 5.0 [1.4] vs 4.3 [1.6]; P = .005), and smaller reduction in NAS (-0.2 [2] vs -0.9 [2]; P < .001) were associated with progression to advanced (stage 3-4) fibrosis vs those without progression to stage 3 to 4 fibrosis. Fibrosis regression was associated with lower baseline insulin level (20 vs 33 μU/mL; P = .02) and decrease in all NAS components (steatosis grade -0.8 [0.1] vs -0.3 [0.9]; P < .001; lobular inflammation -0.5 [0.8] vs -0.2 [0.9]; P < .001; ballooning -0.7 [1.1] vs -0.1 [0.9]; P < .001). Only baseline aspartate aminotransferase (AST) levels were associated with fibrosis regression vs no change and progression vs no change on multivariable regression: baseline AST (regression: conditional odds ratio [cOR], 0.6 per 10 U/L AST; 95% CI, 0.4-0.7; P < .001; progression: cOR, 1.3; 95% CI, 1.1-1.5; P = .002). Changes in the AST level, alanine aminotransferase (ALT) level, and NAS were also associated with fibrosis regression and progression (ΔAST level: regression, cOR, 0.9; 95% CI, 0.6-1.2; P = .47; progression, cOR, 1.3; 95% CI, 1.0-1.6; P = .02; ΔALT level: regression, cOR, 0.7 per 10 U/L AST; 95% CI, 0.5-0.9; P = .002; progression, cOR, 1.0 per 10 U/L AST; 95% CI, 0.9-1.2; P = .93; ΔNAS: regression, cOR, 0.7; 95% CI, 0.6-0.9; P = .001; progression, cOR, 1.3; 95% CI, 1.1-1.5; P = .01).
Improvement or worsening of disease activity may be associated with fibrosis regression or progression, respectively, in NAFLD.
Journal Article
Changes in diet quality and home food environment in preschool children following weight management
by
McCullough, Mary Beth
,
Ittenbach, Richard F.
,
Simon, Stacey L.
in
Analysis
,
Behavior modification
,
Behavior Therapy
2019
Background
Family-based obesity treatment interventions can successfully reduce energy intake in preschoolers. An implicit goal of obesity treatment interventions is to improve diet quality, but diet quality has been less examined as a treatment outcome in studies of preschoolers. The purpose of this study was to conduct a secondary analysis comparing the change in diet quality and home food environment in preschoolers assigned to a behavioral family-based obesity intervention (LAUNCH), motivational interviewing (MI) condition, or standard care (STC) condition.
Methods
Three 24-h dietary recalls were completed at baseline and 6-months and were analyzed using NDS-R software; diet quality was assessed using the Healthy Eating Index-2010 (HEI-2010). Availability of foods and beverages in the home was assessed through direct observation using the Home Health Environment tool that classifies foods and beverages as ‘red’ or ‘green’ based upon fat and sugar content. Repeated measures linear mixed effects models were used to examine changes in diet quality and home food environment between conditions (LAUNCH, MI, STC).
Results
At 6-months, preschoolers in the LAUNCH condition had a higher HEI-2010 total score (62.8 ± 13.7) compared to preschoolers in the MI (54.7 ± 13.4,
P
= 0.022) and STC (55.8 ± 11.6,
P
= 0.046) conditions. Regarding the home food environment, families in LAUNCH had significantly less ‘red’ foods in their home at 6-months (12.5 ± 3.4 ‘red’ foods) compared to families in MI (14.0 ± 3.7 ‘red’ foods,
P
= 0.030), and STC (14.3 ± 3.4 ‘red’ foods,
P
= 0.006). There were no statistically significant differences across home food environments for number of ‘green’ foods.
Conclusion
Family-based obesity treatment interventions for preschoolers can improve overall diet quality and alter the home food environment through reductions in ‘red’ foods.
Trial registration
Clinicaltrials.gov,
NCT01546727
. Registered March 7, 2012.
Journal Article
Landsat imagery reveals declining clarity of Maine's lakes during 1995–2010
by
McCullough, Ian M.
,
Loftin, Cynthia S.
,
Sader, Steven A.
in
Artificial satellites
,
Calibration
,
change detection
2013
Water clarity is a strong indicator of regional water quality. Unlike other common water-quality metrics, such as chlorophyll a, total P, or trophic status, clarity can be accurately and efficiently estimated remotely on a regional scale. Satellite-based remote sensing is useful in regions with many lakes where traditional field-sampling techniques may be prohibitively expensive. Repeated sampling of easily accessed lakes can lead to spatially irregular, nonrandom samples of a region. Remote sensing remedies this problem. We applied a remote monitoring protocol we had previously developed for Maine lakes >8 ha based on Landsat satellite data recorded during 1995–2010 to identify spatial and temporal patterns in Maine lake clarity. We focused on the overlapping region of Landsat paths 11 and 12 to increase availability of cloud-free images in August and early September, a period of relative lake stability and seasonal poor-clarity conditions well suited for annual monitoring. We divided Maine into 3 regions (northeastern, south-central, western) based on morphometric and chemical lake features. We found a general decrease in average statewide lake clarity from 4.94 to 4.38 m during 1995–2010. Water clarity ranged from 4 to 6 m during 1995–2010, but it decreased consistently during 2005–2010. Clarity in both the northeastern and western lake regions has decreased from 5.22 m in 1995 to 4.36 and 4.21 m, respectively, in 2010, whereas lake clarity in the south-central lake region (4.50 m) has not changed since 1995. Climate change, timber harvesting, or watershed morphometry may be responsible for regional water-clarity decline. Remote sensing of regional water clarity provides a more complete spatial perspective of lake water quality than existing, interest-based sampling. However, field sampling done under existing monitoring programs can be used to calibrate accurate models designed to estimate water clarity remotely.
Journal Article