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1.  Portion Size Variably Affects Food Intake of 6-year-old and 4-year-old Children in Kunming, China 
Appetite  2013;69:31-38.
Age and portion size have been found to influence food intake in American children but have not been examined in an international context. This study evaluated the association between age and the effects of portion size on the food intake of kindergarteners in Kunming, China. Using a within-subjects crossover design in a classroom setting, 173 children in two age groups, mean age 4.2 years and 6.1 years, were served a predefined reference, small (-30%) and large (+30%) portion of rice, vegetables, and a protein source during lunchtime over three consecutive days. Each portion was weighed before and after the meal to determine amount of food consumed. Linear mixed modeling, controlling for repeated measures and clustering by classroom, was used to compare food intake under small and large portion size conditions to the reference portion. Children ate significantly less food when served small portions. When served a large portion, 6-year-old children increased food intake while 4-year-old children decreased food intake in comparison to the reference portion. Findings indicate that portion size affects food intake in Chinese children 4- to 6-years old. Older children show larger increases in food intake with increased portion size than do younger children.
PMCID: PMC4319705  PMID: 23702260
Portion size; children; China; dietary intake; preschool; kindergarten; obesity
2.  Ear for recovery: protocol for a prospective study on parent–child communication and psychological recovery after paediatric injury 
BMJ Open  2015;5(2):e007393.
One in six children who have been admitted to hospital with an injury develop persistent stress symptoms that put their development at risk. Parents play a crucial role in children's psychological recovery, however, it is unknown how specific parenting behaviours can help or hinder. We aim to describe the nature and quantity of parent–child communication after a child has been injured, and to examine how these interactions are related to children's psychological recovery.
Methods and analysis
We are conducting a prospective observational study among children aged 3–16 years, who have been admitted to a tertiary children's hospital with a serious injury. Data collection involves a naturalistic observation of spontaneous, everyday parent–child communication at home, shortly after discharge, and an assessment of children's psychological recovery at 6 weeks and 3 months post-injury. Main analyses comprise descriptive statistics, cluster analysis and analyses of variance.
Ethics and dissemination
This study has been approved by the Human Research Ethics Committee of the Royal Children's Hospital Melbourne (33103) and Monash University Human Research Ethics Committee (CF13/2515—2013001322). We aim to disseminate the findings through international peer-reviewed journals, international conferences and social media. Participants will be sent a summary of the overall study findings.
PMCID: PMC4322211  PMID: 25652805
4.  Methods for Assessing and Representing Mammographic Density: An Analysis of 4 Case-Control Studies 
American Journal of Epidemiology  2013;179(2):236-244.
To maximize statistical power in studies of mammographic density and breast cancer, it is advantageous to combine data from several studies, but standardization of the density assessment is desirable. Using data from 4 case-control studies, we describe the process of reassessment and the resulting correlation between values, identify predictors of differences in density readings, and evaluate the strength of the association between mammographic density and breast cancer risk using different representations of density values. The pooled analysis included 1,699 cases and 2,422 controls from California (1990–1998), Hawaii (1996–2003), Minnesota (1992–2001), and Japan (1999–2003). In 2010, a single reader reassessed all images for mammographic density using Cumulus software (Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada). The mean difference between original and reassessed percent density values was −0.7% (95% confidence interval: −1.1, −0.3), with a correlation of 0.82 that varied by location (r = 0.80–0.89). Case status, weight status, age, parity, density assessment method, mammogram view, and race/ethnicity were significant determinants of the difference between original and reassessed values; in combination, these factors explained 9.2% of the variation. The associations of mammographic density with breast cancer and the model fits were similar using the original values and the reassessed values but were slightly strengthened when a calibrated value based on 100 reassessed radiographs was used.
PMCID: PMC3873107  PMID: 24124193
breast cancer; epidemiologic methods; ethnicity; mammographic density; pooling; risk
5.  Pathological Narcissism and Interpersonal Behavior in Daily Life 
Personality disorders  2012;4(4):315-323.
The Cognitive-Affective Processing System (CAPS) has been proposed as a useful meta-framework for integrating contextual differences in situations with individual differences in personality pathology. In this article, we evaluated the potential of combining the CAPS meta-framework and contemporary interpersonal theory to investigate how individual differences in pathological narcissism influenced interpersonal functioning in daily life. University students (N = 184) completed event-contingent reports about interpersonal interactions across a 7-day diary study. Using multilevel regression models, we found that combinations of narcissistic expression (grandiosity, vulnerability) were associated with different interpersonal behavior patterns reflective of interpersonal dysfunction. These results are among the first to empirically demonstrate the usefulness of the CAPS model to conceptualize personality pathology through the patterning of if-then interpersonal processes.
PMCID: PMC4282772  PMID: 23205698
6.  Metformin Use and Endometrial Cancer Survival 
Gynecologic oncology  2013;132(1):236-240.
Impaired glucose tolerance and diabetes are risk factors for the development of uterine cancer. Although greater progression free survival among diabetic patients with ovarian and breast cancer using metformin have been reported, no studies have assessed the association of metformin use with survival in women with endometrial cancer (EC).
We conducted a single-institution retrospective cohort study of all patients treated for uterine cancer from January 1999 through December 2009. Demographic, medical, social, and survival data were abstracted from medical records and the national death registry. Overall survival (OS) was estimated using Kaplan-Meier methods. Cox models were utilized for multivariate analysis. All statistical tests were two-sided.
Of 985 patients, 114 (12%) had diabetes and were treated with metformin, 136 (14%) were diabetic but did not use metformin, and 735 (74%) had not been diagnosed with diabetes. Greater OS was observed in diabetics with non-endometrioid EC who used metformin than in diabetic cases not using metformin and non-endometrioid EC cases without diabetes (log rank test (p=0.02)). This association remained significant (hazard ratio = 0.54, 95% CI: 0.30–0.97, p<0.04) after adjusting for age, clinical stage, grade, chemotherapy treatment, radiation treatment and presence of hyperlipidemia in multivariate analysis. No association between metformin use and OS in diabetics with endometrioid histology was observed.
Diabetic EC patients with non-endometrioid tumors who used metformin had lower risk of death than women with EC who did not use metformin. These data suggest that metformin might be useful as adjuvant therapy for non-endometrioid EC.
PMCID: PMC3904540  PMID: 24189334
Metformin; endometrial cancer; non-endometrioid; adjuvant therapy; retrospective cohort study
7.  Effect of Variations to a Simulated System of Straw Phonation Therapy on Aerodynamic Parameters Using Excised Canine Larynges 
Summary: Objectives/Hypothesis
Resonance tubes are commonly used in voice therapy. These devices modify supraglottal impedance, potentially decreasing the aerodynamic power necessary for phonation. We modeled phonation with resonance tubes in excised larynges and evaluated the effects of varying tube width, tube length, and flow input on phonation threshold pressure (PTP) and phonation threshold flow (PTF). We hypothesized that the increased vocal economy observed in human subjects and several other models would be observed in excised larynges.
Study Design
Repeated measures excised canine larynx bench experiment with each larynx serving as own control.
Nine conditions were evaluated, namely control, two tube diameters (17.5 and 6.5 mm), three tube lengths (7.8, 15.0, and 30.0 cm), and three levels of flow input (80, 114, and 200 mL/s). Aerodynamic data were collected for 11 excised canine larynges attached to an artificial vocal tract, and results from each experimental configuration were compared with control.
A significant decrease in average PTP occurred compared with control for the 114- and 200-mL/s flow inputs, 30-cm extension, and 17.5- and 6.5-mm constrictions. Average PTF decreased compared with control for every configuration, although statistically significant changes were only observed for 200-mL/s flow and 6.5-mm constriction.
Knowledge regarding the effect of vocal tract alterations could be clinically useful in determining the optimal “straw” configuration for voice therapy. Further exploration of the relationships among width, length, and flow input could provide theoretical support for the development of new therapies and resonance tube devices.
PMCID: PMC3951877  PMID: 24286626
Resonance tube; Straw phonation therapy; Phonation threshold flow; Phonation threshold pressure; Excised larynx
8.  Subclassification of Newly Diagnosed Glioblastomas through an Immunohistochemical Approach 
PLoS ONE  2014;9(12):e115687.
Molecular signatures in Glioblastoma (GBM) have been described that correlate with clinical outcome and response to therapy. The Proneural (PN) and Mesenchymal (MES) signatures have been identified most consistently, but others including Classical (CLAS) have also been reported. The molecular signatures have been detected by array techniques at RNA and DNA level, but these methods are costly and cannot take into account individual contributions of different cells within a tumor. Therefore, the aim of this study was to investigate whether subclasses of newly diagnosed GBMs could be assessed and assigned by application of standard pathology laboratory procedures. 123 newly diagnosed GBMs were analyzed for the tumor cell expression of 23 pre-identified proteins and EGFR amplification, together allowing for the subclassification of 65% of the tumors. Immunohistochemistry (IHC)-based profiling was found to be analogous to transcription-based profiling using a 9-gene transcriptional signature for PN and MES subclasses. Based on these data a novel, minimal IHC-based scheme for subclass assignment for GBMs is proposed. Positive staining for IDH1R132H can be used for PN subclass assignment, high EGFR expression for the CLAS subtype and a combined high expression of PTEN, VIM and/or YKL40 for the MES subclass. The application of the proposed scheme was evaluated in an independent tumor set, which resulted in similar subclass assignment rates as those observed in the training set. The IHC-based subclassification scheme proposed in this study therefore could provide very useful in future studies for stratification of individual patient samples.
PMCID: PMC4278713  PMID: 25546404
9.  Physical Activity Self-Monitoring and Weight Loss: 6-Month Results of the SMART Trial 
Weight loss has been associated with higher physical activity (PA) levels and frequent dietary self-monitoring. Less is known about how PA self-monitoring affects adherence to PA goals, PA levels and weight change.
The SMART Trial is a clinical weight loss trial in which 210 overweight adults were randomized equally to one of three arms: 1) paper record (PR); 2) personal digital assistant with self-monitoring software (PDA); and 3) PDA with daily tailored feedback message (PDA+FB). PA self-monitoring and adherence to PA goals were based on entries in weekly submitted diaries. PA levels were measured via self-report by the past 6 month Modifiable Activity Questionnaire at baseline and 6 months.
Data are presented on 189 participants with complete 6-month PA data [84% female, 77% White, mean age: 47.3 ± 8.8 years, mean BMI: 34.1 ± 4.5 kg/m2]. Median PA level was 7.96 MET-hr-wk−1 at baseline and 13.4 MET-hr-wk−1 at 6 months, with significant PA increases in all three arms. PDA+FB arm had a higher mean number of weekly self-monitoring entries than the PR arm (3.4 vs. 2.4; p=0.003) and were more likely to maintain high (i.e., 100%) adherence to PA goals over time than the PDA (p=0.02) or PR arms (p=0.0003). Both PA self-monitoring and adherence to PA goals were related to higher PA levels at 6 months. A higher mean rate of PA self-monitoring was associated with a greater percentage of weight decrease (rho=−0.49; p<0.0001) at 6 months.
PA self-monitoring and adherence to PA goals were more likely in participants in the PDA+FB arm and in turn predicted higher PA levels and weight loss.
PMCID: PMC4266405  PMID: 21200337
adherence; feedback; lifestyle change; technology
10.  Dim light melatonin onset in alcohol-dependent men and women compared to healthy controls 
Chronobiology international  2012;29(1):35-42.
Sleep disturbances in alcohol-dependent (AD) individuals may persist despite abstinence from alcohol and can influence the course of disorder. Although the mechanisms for their sleep disturbances are not well understood and some evidence suggests dysregulation of circadian rhythms, dim-light melatonin onset (DLMO) has not previously been assessed in AD vs. healthy control (HC) individuals in a sample that varied by sex and race.
Fifty-two AD participants (mean age 36.0 ± 11.0 years, 10 women) who were 3–12 weeks since their last drink (mean abstinence 57.9 ± 19.3 days) and 19 age- and sex-matched HCs (mean age 34.4 ± 10.6 years, 5 women) participated. Following a 23:00 – 06:00 h at-home sleep schedule for at least 5 days, and screening/baseline nights in the sleep laboratory, participants underwent a 3-hr extension of wakefulness (02:00 h bedtime) during which salivary melatonin samples were collected every 30 minutes beginning at 19:30 h. The time of DLMO was the primary measure of circadian physiology and was assessed with two commonly used methodologies.
There was a slower rate of rise and a lower maximal amplitude in the AD group. DLMO varied by methodology used. Using 3 pg/ml as a threshold, no significant differences between the AD and HC groups were found. Using two standard deviations above the mean of the first 3 samples, AD DLMO occurred later 21:02 (SD=0:41) than HC 20:44 (SD=0:21) t=-2.4, (p=.02).
While melatonin in the AD group appears to have a slower rate of rise, using well-established criteria to assess salivary DLMO did not reveal differences between AD and HC participants. Only when capturing melatonin when it is already rising was DLMO significantly delayed by a mean 18 min in ADs. Future circadian analyses on alcoholics should account for these methodological caveats
PMCID: PMC4258345  PMID: 22217099
Alcohol; Melatonin; Men; Women; Sleep; Dim light melatonin onset (DLMO)
11.  Chemotherapy-induced amenorrhea: a prospective study of brain activation changes and neurocognitive correlates 
Brain imaging and behavior  2013;7(4):10.1007/s11682-013-9240-5.
Chemotherapy-induced amenorrhea (CIA) often occurs in pre- and peri-menopausal BC patients, and while cancer/chemotherapy and abrupt estrogen loss have separately been shown to affect cognition and brain function, studies of the cognitive effects of CIA are equivocal, and its effects on brain function are unknown. Functional MRI (fMRI) during a working memory task was used to prospectively assess the pattern of brain activation and deactivation prior to and one month after chemotherapy in BC patients who experienced CIA (n=9), post-menopausal BC patients undergoing chemotherapy (n=9), and pre- and post-menopausal healthy controls (n=6 each). Neurocognitive testing was also performed at both time points. Repeated measures general linear models were used to assess statistical significance, and age was a covariate in all analyses. We observed a group-by-time interaction in the combined magnitudes of brain activation and deactivation (p = 0.006): the CIA group increased in magnitude from baseline to post-treatment while other groups maintained similar levels over time. Further, the change in brain activity magnitude in CIA was strongly correlated with change in processing speed neurocognitive testing score (r=0.837 p=0.005), suggesting this increase in brain activity reflects effective cognitive compensation. Our results demonstrate prospectively that the pattern of change in brain activity from pre- to post-chemotherapy varies according to pre-treatment menopausal status. Cognitive correlates add to the potential clinical significance of these findings. These findings have implications for risk appraisal and development of prevention or treatment strategies for cognitive changes in CIA.
PMCID: PMC3819410  PMID: 23793983
breast cancer; chemotherapy; amenorrhea; functional MRI
12.  Small molecule annotation for the Protein Data Bank 
The Protein Data Bank (PDB) is the single global repository for three-dimensional structures of biological macromolecules and their complexes, and its more than 100 000 structures contain more than 20 000 distinct ligands or small molecules bound to proteins and nucleic acids. Information about these small molecules and their interactions with proteins and nucleic acids is crucial for our understanding of biochemical processes and vital for structure-based drug design. Small molecules present in a deposited structure may be attached to a polymer or may occur as a separate, non-covalently linked ligand. During curation of a newly deposited structure by wwPDB annotation staff, each molecule is cross-referenced to the PDB Chemical Component Dictionary (CCD). If the molecule is new to the PDB, a dictionary description is created for it. The information about all small molecule components found in the PDB is distributed via the ftp archive as an external reference file. Small molecule annotation in the PDB also includes information about ligand-binding sites and about covalent and other linkages between ligands and macromolecules. During the remediation of the peptide-like antibiotics and inhibitors present in the PDB archive in 2011, it became clear that additional annotation was required for consistent representation of these molecules, which are quite often composed of several sequential subcomponents including modified amino acids and other chemical groups. The connectivity information of the modified amino acids is necessary for correct representation of these biologically interesting molecules. The combined information is made available via a new resource called the Biologically Interesting molecules Reference Dictionary, which is complementary to the CCD and is now routinely used for annotation of peptide-like antibiotics and inhibitors.
PMCID: PMC4243272  PMID: 25425036
13.  Dll4 Blockade Potentiates the Anti-Tumor Effects of VEGF Inhibition in Renal Cell Carcinoma Patient-Derived Xenografts 
PLoS ONE  2014;9(11):e112371.
The Notch ligand Delta-like 4 (Dll4) is highly expressed in vascular endothelium and has been shown to play a pivotal role in regulating tumor angiogenesis. Blockade of the Dll4-Notch pathway in preclinical cancer models has been associated with non-productive angiogenesis and reduced tumor growth. Given the cross-talk between the vascular endothelial growth factor (VEGF) and Delta-Notch pathways in tumor angiogenesis, we examined the activity of a function-blocking Dll4 antibody, REGN1035, alone and in combination with anti-VEGF therapy in renal cell carcinoma (RCC).
Methods and Results
Severe combined immunodeficiency (SCID) mice bearing patient-derived clear cell RCC xenografts were treated with REGN1035 and in combination with the multi-targeted tyrosine kinase inhibitor sunitinib or the VEGF blocker ziv-aflibercept. Immunohistochemical and immunofluorescent analyses were carried out, as well as magnetic resonance imaging (MRI) examinations pre and 24 hours and 2 weeks post treatment. Single agent treatment with REGN1035 resulted in significant tumor growth inhibition (36–62%) that was equivalent to or exceeded the single agent anti-tumor activity of the VEGF pathway inhibitors sunitinib (38–54%) and ziv-aflibercept (46%). Importantly, combination treatments with REGN1035 plus VEGF inhibitors resulted in enhanced anti-tumor effects (72–80% growth inhibition), including some tumor regression. Magnetic resonance imaging showed a marked decrease in tumor perfusion in all treatment groups. Interestingly, anti-tumor efficacy of the combination of REGN1035 and ziv-aflibercept was also observed in a sunitinib resistant ccRCC model.
Overall, these findings demonstrate the potent anti-tumor activity of Dll4 blockade in RCC patient-derived tumors and a combination benefit for the simultaneous targeting of the Dll4 and VEGF signaling pathways, highlighting the therapeutic potential of this treatment modality in RCC.
PMCID: PMC4231048  PMID: 25393540
14.  Inter-subject alignment of human cortical anatomy using functional connectivity 
NeuroImage  2013;81:400-411.
Inter-subject alignment of functional MRI (fMRI) data is necessary for group analyses. The standard approach to this problem matches anatomical features of the brain, such as major anatomical landmarks or cortical curvature. Precise alignment of functional cortical topographies, however, cannot be derived using only anatomical features.
We propose a new inter-subject registration algorithm that aligns intra-subject patterns of functional connectivity across subjects. We derive functional connectivity patterns by correlating fMRI BOLD time-series, measured during movie viewing, between spatially remote cortical regions. We validate our technique extensively on real fMRI experimental data and compare our method to two state-of-the-art inter-subject registration algorithms. By cross-validating our method on independent datasets, we show that the derived alignment generalizes well to other experimental paradigms.
PMCID: PMC3729877  PMID: 23685161
Inter-subject registration; Functional connectivity; Surface-based methods
15.  Validation of Anaphylaxis in the Food and Drug Administration's Mini-Sentinel 
Pharmacoepidemiology and drug safety  2013;22(11):1205-1213.
To develop and validate the positive predictive value (PPV) of an algorithm to identify anaphylaxis using health plan administrative and claims data. Previously published positive predictive values (PPVs) for anaphylaxis using ICD-9-CM codes range from 52-57%.
We conducted a retrospective study using administrative and claims data from eight health plans. Using diagnosis and procedure codes, we developed an algorithm to identify potential cases of anaphylaxis from the Mini-Sentinel Distributed Database between January 2009 and December 2010. A random sample of medical charts (N=150) was identified for chart abstraction. Two physician adjudicators reviewed each potential case. Using physician adjudicator judgments on whether the case met diagnostic criteria for anaphylaxis, we calculated a PPV for the algorithm.
Of the 122 patients for whom complete charts were received, 77 were judged by physician adjudicators to have anaphylaxis. The PPV for the algorithm was 63.1% (95% CI: 53.9%-71.7%), using the clinical criteria by Sampson as the gold standard. The PPV was highest for inpatient encounters with ICD-9-CM codes of 995.0 or 999.4. By combining only the top performing ICD-9-CM codes, we identified an algorithm with a PPV of 75.0%, but only 66% of cases of anaphylaxis were identified using this modified algorithm.
The PPV for the ICD-9-CM-based algorithm for anaphylaxis was slightly higher than PPV estimates reported in prior studies, but remained low. We were able to identify an algorithm which optimized the PPV but demonstrated lower sensitivity for anaphylactic events.
PMCID: PMC4113322  PMID: 24038742
anaphylaxis; serious allergic reaction; validation; administrative data; Food and Drug administration; Mini-Sentinel
16.  Sedentary Behavior as a Daily Process Regulated by Habits and Intentions 
Sedentary behavior is a health risk but little is known about the motivational processes that regulate daily sedentary behavior. This study was designed to test a dual-process model of daily sedentary behavior, with an emphasis on the role of intentions and habits in regulating daily sedentary behavior.
College students (N = 128) self-reported on their habit strength for sitting and completed a 14-day ecological momentary assessment study that combined daily diaries for reporting motivation and behavior with ambulatory monitoring of sedentary behavior using accelerometers.
Less than half of the variance in daily sedentary behavior was attributable to between-person differences. People with stronger sedentary habits reported more sedentary behavior on average. People whose intentions for limiting sedentary behavior were stronger, on average, exhibited less self-reported sedentary behavior (and marginally less monitored sedentary behavior). Daily deviations in those intentions were negatively associated with changes in daily sedentary behavior (i.e., stronger than usual intentions to limit sedentary behavior were associated with reduced sedentary behavior). Sedentary behavior also varied within-people as a function of concurrent physical activity, the day of week, and the day in the sequence of the monitoring period.
Sedentary behavior was regulated by both automatic and controlled motivational processes. Interventions should target both of these motivational processes to facilitate and maintain behavior change. Links between sedentary behavior and daily deviations in intentions also indicate the need for ongoing efforts to support controlled motivational processes on a daily basis.
PMCID: PMC4134884  PMID: 23477579
sitting; inactivity; goal; perception-behavior link
17.  The Effect of Odor Valence on Olfactory Performance in Schizophrenia Patients, Unaffected Relatives and At-Risk Youth 
Journal of psychiatric research  2013;47(11):1636-1641.
Given the presence of odor identification impairment in individuals with schizophrenia and recent evidence of aberrant odor hedonic processing, the aim of this investigation was to examine the influence of valence and intensity on odor identification in schizophrenia patients, their first-degree family members, and young persons at clinical risk for psychosis. Participants completed the 16-item Sniffin’ Stick Odor Identification Test. A logistic regression was conducted to assess the influence of valence and intensity on odor identification accuracy. Identification performance in the schizophrenia patients and youths at clinical risk for psychosis was significantly influenced by odor valence, but not intensity. Identification accuracy in first-degree family members was not influenced by valence or intensity. These data suggest that abnormalities in odor valence perception may represent an environmentally-mediated marker for hedonic disturbance that could have predictive utility in future conversion to psychosis. Further research examining the utility of odor valence measures as markers for psychosis risk are warranted.
PMCID: PMC4198303  PMID: 23953754
olfaction; anhedonia; emotion; schizophrenia prodrome; smell identification
18.  Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression 
Kote-Jarai, Zsofia | Saunders, Edward J. | Leongamornlert, Daniel A. | Tymrakiewicz, Malgorzata | Dadaev, Tokhir | Jugurnauth-Little, Sarah | Ross-Adams, Helen | Al Olama, Ali Amin | Benlloch, Sara | Halim, Silvia | Russell, Roslin | Dunning, Alison M. | Luccarini, Craig | Dennis, Joe | Neal, David E. | Hamdy, Freddie C. | Donovan, Jenny L. | Muir, Ken | Giles, Graham G. | Severi, Gianluca | Wiklund, Fredrik | Gronberg, Henrik | Haiman, Christopher A. | Schumacher, Fredrick | Henderson, Brian E. | Le Marchand, Loic | Lindstrom, Sara | Kraft, Peter | Hunter, David J. | Gapstur, Susan | Chanock, Stephen | Berndt, Sonja I. | Albanes, Demetrius | Andriole, Gerald | Schleutker, Johanna | Weischer, Maren | Canzian, Federico | Riboli, Elio | Key, Tim J. | Travis, Ruth C. | Campa, Daniele | Ingles, Sue A. | John, Esther M. | Hayes, Richard B. | Pharoah, Paul | Khaw, Kay-Tee | Stanford, Janet L. | Ostrander, Elaine A. | Signorello, Lisa B. | Thibodeau, Stephen N. | Schaid, Dan | Maier, Christiane | Vogel, Walther | Kibel, Adam S. | Cybulski, Cezary | Lubinski, Jan | Cannon-Albright, Lisa | Brenner, Hermann | Park, Jong Y. | Kaneva, Radka | Batra, Jyotsna | Spurdle, Amanda | Clements, Judith A. | Teixeira, Manuel R. | Govindasami, Koveela | Guy, Michelle | Wilkinson, Rosemary A. | Sawyer, Emma J. | Morgan, Angela | Dicks, Ed | Baynes, Caroline | Conroy, Don | Bojensen, Stig E. | Kaaks, Rudolf | Vincent, Daniel | Bacot, François | Tessier, Daniel C. | Easton, Douglas F. | Eeles, Rosalind A.
Human Molecular Genetics  2013;22(20):4239.
PMCID: PMC3871151
19.  A Daily Process Analysis of Intentions and Physical Activity in College Students 
Social-cognitive theories, such as the theory of planned behavior, posit intentions as proximal influences on physical activity (PA). This paper extends those theories by examining within-person variation in intentions and moderate-vigorous physical activity (MVPA) as a function of the unfolding constraints in people’s daily lives (e.g., perceived time availability, fatigue, soreness, weather, overeating). College students (N = 63) completed a 14-day diary study rating daily motivation, contextual constraints, and PA over the internet. Key findings from multilevel analyses were that (1) between-person differences represented 46% and 33% of the variability in daily MVPA intentions and behavior, respectively, (2) attitudes, injunctive norms, self-efficacy, perceptions of limited time availability, and weekend status predicted daily changes in intention strength, and (3) daily changes in intentions, perceptions of limited time availability, and weekend status predicted day-to-day changes in MVPA. Embedding future motivation and PA research in the context of people’s daily lives will advance understanding of individual PA change processes.
PMCID: PMC4104787  PMID: 24197717
self-regulation; planned behavior; intraindividual
20.  Mesenchymal Differentiation Mediated by NF-κB Promotes Radiation Resistance in Glioblastoma 
Cancer cell  2013;24(3):10.1016/j.ccr.2013.08.001.
Despite extensive study, few therapeutic targets have been identified for glioblastoma (GBM). Here we show that patient derived glioma sphere cultures (GSCs) that resemble either the proneural (PN) or mesenchymal (MES) transcriptomal subtypes differ significantly in their biological characteristics. Moreover, we found that a subset of the PN GSCs undergo differentiation to a MES state in a TNFα/NF-κB dependent manner with an associated enrichment of CD44 subpopulations and radio-resistant phenotypes. We present data to suggest that the tumor microenvironment cell types such as macrophages/microglia may play an integral role in this process. We further show that the MES signature, CD44 expression, and NF-κB activation correlate with poor radiation response and shorter survival in patients with GBM.
PMCID: PMC3817560  PMID: 23993863
21.  Acute Myocardial Infarction Quality of Care: The Strong Heart Study 
Ethnicity & disease  2011;21(3):294-300.
Evaluate the quality of care provided patients with acute myocardial infarction and compare with similar national and regional data.
Case series.
The Strong Heart Study has extensive population-based data related to cardiovascular events among American Indians living in three rural regions of the United States.
Acute myocardial infarction cases (72) occurring between 1/1/2001 and 12/31/2006 were identified from a cohort of 4549 participants.
Outcome measures
The proportion of cases that were provided standard quality of care therapy, as defined by the Healthcare Financing Administration and other national organizations.
The provision of quality services, such as administration of aspirin on admission and at discharge, reperfusion therapy within 24 hours, prescription of beta blocker medication at discharge, and smoking cessation counseling were found to be 94%, 91%, 92%, 86% and 71%, respectively. The unadjusted, 30 day mortality rate was 17%.
Despite considerable challenges posed by geographic isolation and small facilities, process measures of the quality of acute myocardial infarction care for participants in this American Indian cohort were comparable to that reported for Medicare beneficiaries nationally and within the resident states of this cohort.
PMCID: PMC4151497  PMID: 21942161
Acute Myocardial Infarction; Ethnicity; Guideline Adherence; Outcome and Process Assessment; Quality Indicators
22.  FAK inhibition with small molecule inhibitor Y15 decreases viability, clonogenicity, and cell attachment in thyroid cancer cell lines and synergizes with targeted therapeutics 
Oncotarget  2014;5(17):7945-7959.
Focal adhesion kinase (FAK) is up-regulated in thyroid cancer and small molecule FAK scaffolding inhibitor, Y15, was shown to decrease cancer growth in vitro and in vivo. We sought to test the effectiveness of Y15 in thyroid cancer cell lines, profile gene expression with Y15 compared with clinical trial FAK inhibitor PF-04554878, and use Y15 in novel drug combinations. Cell viability was decreased in a dose dependent manner in four thyroid cancer cell lines with Y15 and with higher doses in PF-04554878. Y397 FAK and total FAK were decreased with Y15 and decreased less with PF-04554878. Detachment and necrosis were increased in a dose-dependent manner in all cell lines with Y15. Clonogenicity was decreased in a dose-dependent manner for both Y15 and PF-04554878. We compared gene profiles between papillary thyroid cell lines, TPC1, BCPAP and K1, and 380, 109, and 74 genes were significantly >2-fold changed with Y15 treatment, respectively. Common up-regulated genes were involved in apoptosis, cell cycle, transcription and heat shock; down-regulated genes were involved in cell cycle, cell-to-cell interactions, and cancer stem cell markers. We also compared gene profiles of TT cells treated with Y15 versus PF-04554878. Y15 caused 144 genes to change over 4 fold and PF-04554878 caused 208 gene changes >4-fold (p<0.05). Among genes changed 4 fold, 11 were shared between the treatments, including those involved in metabolism, cell cycle, migration and transcription. Y15 demonstrated synergy with PF-04554878 in TT cells and also synergy with Cabozantinib, Sorafenib, Pazopanib, and strong synergy with Sunitinib in resistant K1 cells. This report revealed the biological effect of Y15 inhibitor, detected the unique and common gene signature profiles in response to Y15 in 4 different thyroid cancer cell lines, demonstrated differential response changes with Y15 and PF-04554878 treatment, and showed the synergy of Y15 with PF-04554878, Cabozantinib, Sorafenib, Pazopanib, and Sunitinib.
PMCID: PMC4202172  PMID: 25277206
24.  Unpacking the Feel Good Effect of Free-Time Physical Activity: Between- and Within-Person Associations with Pleasant-Activated Feeling States 
Physical activity is a widely accessible and effective tool for improving well-being. This study aimed to unpack the feel good effects of free-time physical activity. Multilevel models were applied to repeated measures of daily free-time physical activity and four types of feeling states obtained from 190 undergraduate students. Physical activity was not associated with pleasant-deactivated, unpleasant-activated, or unpleasant-deactivated feelings. People who were more physically active overall had higher pleasant-activated feelings than people who were less physically active, and on days when people were more physically active than was typical for them, they reported higher levels of pleasant-activated feelings. Both the between- and within-person associations remained significant after controlling for day-of-week, sleep quality, and carryover effects of previous day free-time physical activity and feeling states. Results suggest that both increases in overall levels and acute bouts of free-time physical activity are associated with increases in feelings of pleasant-activation.
PMCID: PMC4144026  PMID: 22262710
positive-activation; mental health; exercise; daily diary
25.  The Dynamic Nature of Physical Activity Intentions: A Within-Person Perspective on Intention-Behavior Coupling 
The intention-behavior gap has proven to be a vexing problem for theorists and practitioners interested in physical activity. Intention stability is one factor which moderates this gap. This study articulated and tested contrasting views of intention stability as (a) a dynamic characteristic of people that influences assessment error (and therefore the predictive power of intentions), and (b) the product of a dynamic process that unfolds within people over time. Using an ecological momentary assessment design, young adults (N = 30) rated weekly physical activity intentions for 10 weeks and wore pedometers for the first 4 weeks of the study. Substantial within-person variability existed in intentions over both 4- and 10-week intervals, and this variability was not a function of time exclusively. Multilevel modeling revealed that overall intention strength (across weeks) and weekly deviations in intention strength interacted to predict weekday (but not weekend) physical activity. These findings indicate that the person and context interact to selectively couple or decouple intentions from daily physical activity.
PMCID: PMC4137572  PMID: 22262706
self-regulation; motivation; goals; planned behavior; pedometer

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